BR122023025996A2 - AMINO ACID COMPOUNDS, PHARMACEUTICAL COMPOSITION AND KIT COMPRISING THE SAME, THEIR USES, AND THEIR PRODUCTION METHOD - Google Patents

Abstract

The present invention relates to compounds of formula (I), or a salt thereof, wherein R1, G, L1, L2, L3 and Y are as described herein. The compounds of formula (I) and pharmaceutical compositions thereof are inhibitors of one or more of, or both, integrin αVβ1 and integrin αVβ6 which are useful for the treatment of fibrosis, such as non-alcoholic steatohepatitis (NASH), pulmonary fibrosis idiopathic pneumonia (IFF) and non-specific interstitial pneumonia (NSIP).

Description

RELATED REQUESTS

[0001] This application claims the benefit of priority of U.S. Provisional Patent Application No. 62/742,901, filed on October 8, 2018, the entire contents of which are incorporated herein by reference.

FIELD OF INVENTION

[0002] The present invention relates, in general, to therapeutic agents that may be useful as αvβ6 integrin inhibitors. Therapeutic agents can be used in the treatment or prophylactic treatment of fibrosis, such as idiopathic pulmonary fibrosis (IPF) and nonspecific interstitial pneumonia (NSIP).

BACKGROUND

[0003] Fibrosis, a pathological feature of many diseases, is caused by a dysfunction in the body's natural ability to repair damaged tissue. If left untreated, fibrosis can result in scarring of vital organs, causing irreparable damage and eventual organ failure.

[0004] Patients with non-alcoholic fatty liver disease (NAFLD) can progress from simple steatosis to non-alcoholic steatohepatitis (NASH) and then fibrosis. Although liver fibrosis is reversible in its early stages, progressive liver fibrosis can lead to cirrhosis.

[0005] Renal fibrosis, characterized by glomerulosclerosis and tubulointerstitial fibrosis, is the final common manifestation of a wide variety of chronic kidney diseases (CKD). Regardless of the initial causes, progressive CKD often results in widespread tissue scarring that leads to renal parenchymal destruction and end-stage renal failure, a devastating condition requiring dialysis or kidney replacement.

[0006] Scleroderma encompasses a spectrum of complex and variable conditions characterized mainly by fibrosis, vascular changes and autoimmunity. The scleroderma disease spectrum shares the common feature of fibrosis, resulting in hardening or thickening of the skin. For some patients, this hardening only occurs in limited areas, but for others, it can spread to other major organs.

[0007] After myocardial infarction, cardiac structural remodeling is associated with an inflammatory reaction, resulting in the formation of a scar at the site of the infarction. This scar formation is a result of the deposition of fibrotic tissue, which can lead to reduced cardiac function and disruption of electrical activity within the heart.

[0008] Crohn's disease is a chronic disease of unknown etiology that tends to progress even in the context of medical or surgical treatment. Intestinal fibrosis is among the most common complications of Crohn's disease, resulting in the formation of strictures in the small intestine and colon.

[0009] Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive and fibrosing disease of unknown etiology, which occurs in adults and is limited to the lungs. In IPF, lung tissue becomes thick, stiff, and scarred. As pulmonary fibrosis progresses, it becomes more difficult for the lungs to transfer oxygen to the bloodstream and the organs do not receive the oxygen they need to function properly. Currently, IPF affects approximately 200,000 people in the United States, resulting in 40,000 deaths per year. Patients diagnosed with IPF experience progressive shortness of breath and, eventually, complete respiratory failure.

[0010] Primary biliary cholangitis (PBC), also known as primary biliary cirrhosis, is a chronic liver disease that causes liver damage and fibrosis. It results from a slow, progressive destruction of the liver's small bile ducts, causing bile and other toxins to accumulate in the liver, a condition called cholestasis. Over time, this leads to scarring and fibrosis in the liver and biliary tract.

[0011] Nonspecific interstitial pneumonia (NSIP) is a rare disease that affects the tissue that surrounds and separates the tiny air sacs of the lungs. These air sacs, called alveoli, are where the exchange of oxygen and carbon dioxide occurs between the lungs and the bloodstream. Interstitial pneumonia is a disease in which the mesh-like walls of the alveoli become inflamed. The pleura (a thin covering that protects and cushions the lungs and individual lobes of the lungs) can also become inflamed. There are two primary forms of NSIP – cellular and fibrotic. The cellular form is defined mainly by inflammation of the interstitial cells. The fibrotic form is defined by the thickening and scarring of lung tissue. This scarring is known as fibrosis and is irreversible. When lung tissue becomes thickened or scarred, it doesn't work as well. Breathing becomes less efficient and there are lower levels of oxygen in the blood. (Kim et al., Proc. Am. Thorac. Soc. (2006) 3: 285 to 292; Lynch, D., Radiology (2001) 221: 583 to 584; Kinder et al., Am. J. Respir. Crit . Care Med. (2007) 176: 691 to 697)

[0012] The available treatment courses are scarce, as there are currently no options on the market that have been proven to affect the patient's long-term survival or symptoms. There remains a need for treatment of fibrotic diseases.

[0013] Integrin αvβ6 is expressed in epithelial cells and binds to transforming growth factor-β1 latency-associated peptide (TGFβ1) and mediates the activation of TGFβ1. Its expression level is significantly increased after lung and cholangiocyte injury, and it plays a critical role in tissue fibrosis in vivo. Elevated levels are also associated with increased mortality in patients with IPF and NSIP.

[0014] Primary sclerosing cholangitis (PSC) involves bile duct inflammation and fibrosis that obliterates the bile ducts. The resulting impediment to the flow of bile to the intestines can lead to cirrhosis of the liver and subsequent complications such as liver failure and liver cancer. Expression of αvβ6 is elevated in the liver and bile duct of patients with PSC.

[0015] The present disclosure provides αvβ6 integrin inhibitors that may be useful for treating fibrosis.

SUMMARY

[0016] Amino acid compounds that are inhibitors of integrin αvβ6, compositions containing these compounds, and methods for treating diseases mediated by integrin αvβ6, such as fibrotic disease, are disclosed.

[0017] In one aspect, there is provided a compound of formula (I), or any variation thereof, or a salt thereof (e.g., a pharmaceutically acceptable salt thereof), as detailed herein.

[0018] Furthermore, there is provided a pharmaceutical composition comprising a compound of formula (I), or any variation thereof detailed herein, or a salt thereof (e.g., a pharmaceutically acceptable salt thereof) and a carrier or pharmaceutically acceptable excipient.

[0019] In another aspect, there is provided a method for treating a fibrotic disease in an individual (such as a human being) in need thereof, which comprises administering to the individual a therapeutically effective amount of a compound of formula (I), or any variation thereof detailed herein, or a pharmaceutically acceptable salt thereof. In some embodiments, the fibrotic disease or condition is pulmonary, hepatic, renal, cardiac, dermal, or gastrointestinal fibrosis. In other embodiments, the fibrotic disease or condition is idiopathic pulmonary fibrosis, interstitial lung disease, radiation-induced pulmonary fibrosis, non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), alcohol-induced liver fibrosis, Alport syndrome , primary sclerosing cholangitis, primary biliary cholangitis (also known as primary biliary cirrhosis), interstitial lung disease associated with systemic sclerosis, scleroderma (also known as systemic sclerosis), diabetic nephropathy, diabetic kidney disease, focal segmental glomerulosclerosis, chronic kidney disease or disease of Crohn's.

[0020] In another aspect, there is provided a method for delaying the onset and/or development of a fibrotic disease in an individual (such as a human being) who is at risk of developing a fibrotic disease or condition, which comprises administering to the individual a therapeutically effective amount of a compound of formula (I), or any variation thereof detailed herein, or a pharmaceutically acceptable salt thereof. In some embodiments, the disease or condition is pulmonary, hepatic, renal, cardiac, dermal, or gastrointestinal fibrosis. In other embodiments, the fibrotic disease or condition is idiopathic pulmonary fibrosis, interstitial lung disease, radiation-induced pulmonary fibrosis, non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), alcohol-induced liver fibrosis, Alport syndrome , primary sclerosing cholangitis, primary biliary cholangitis (also known as primary biliary cirrhosis), interstitial lung disease associated with systemic sclerosis, scleroderma (also known as systemic sclerosis), diabetic nephropathy, diabetic kidney disease, focal segmental glomerulosclerosis, chronic kidney disease or disease of Crohn's.

[0021] Also provided is a compound of formula (I), or any variation thereof detailed herein, or a pharmaceutical composition thereof, for the treatment of a fibrotic disease.

[0022] Also provided is the use of a compound of formula (I), or any variation thereof detailed herein, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition comprising any of the foregoing, in the manufacture of a medicine for the treatment of a fibrotic disease.

[0023] There is also provided a kit comprising a compound of formula (I), or any variation thereof detailed herein, or a pharmaceutically acceptable salt thereof. In some embodiments, the kit comprises instructions for use in accordance with a method described herein, such as a method of treating a fibrotic disease in an individual.

[0024] In another aspect, a method for preparing a compound of formula (I) or any variation thereof is provided. Also provided are intermediate compounds useful in the synthesis of a compound of formula (I), or any variation thereof.

[0025] It is understood that the aspects and variations described herein also include "consisting of" and/or "consisting essentially of" aspects and variations.

BRIEF DESCRIPTION OF FIGURES

[0026] Figure 1, Table 2 shows the chemical structures for various compounds disclosed in this document. Reference to compound numbers in the table in some cases depicts a particular stereoisomeric form of the compound number, as will be evident from the chemical structure depicted.

[0027] Figure 2, Table B-2 shows biological data for several compounds disclosed in this document.

DETAILED DESCRIPTION

[0028] The invention provides, among others, compounds of formula (I), and variations thereof, pharmaceutical compositions comprising compounds of formula (I), and methods of using such compounds and compositions in the treatment of fibrotic diseases. Also provided are compounds and pharmaceutical compositions comprising salts of compounds of formula (I).

DEFINITIONS

[0029] For use herein, unless clearly indicated otherwise, the use of the terms "one", "an" and the like refers to one or more.

[0030] Reference to "about" a value or parameter in this document includes (and describes) embodiments that are directed to that value or parameter per se. For example, the description referring to "about X" includes the description of "X". Likewise, reference to a value "X" also includes the description of "about X".

[0031] "Alkyl", as used herein, refers to and includes, unless otherwise indicated, a linear (i.e., unbranched) or branched saturated univalent hydrocarbon chain or a combination thereof, which has the designated number of carbon atoms (i.e., C1-C10 means one to ten carbon atoms). Particular alkyl groups are those that have 1 to 20 carbon atoms (a "C1-C20 alkyl"), which have 1 to 10 carbon atoms (a "C1-C10 alkyl"), which have 6 to 10 carbon atoms (a "C6-C10 alkyl"), which have 1 to 6 carbon atoms (a "C1-C6 alkyl"), which have 2 to 6 carbon atoms (a "C2-C6 alkyl"), or which have 1 to 4 carbon atoms (a "C1-C4 alkyl"). Examples of alkyl groups include, but are not limited to, groups such as methyl, ethyl, n-propyl, isopropyl, n-butyl, t-butyl, isobutyl, sec-butyl, n-pentyl, n-hexyl, n-heptyl, n- octyl, n-nonyl, n-decyl and the like.

[0032] "Alkylene", as used herein, refers to the same residues as alkyl, but with bivalency. Particular alkylene groups are those that have 1 to 20 carbon atoms (a "C1-C20 alkylene"), which have 1 to 10 carbon atoms (a "C1-C10 alkylene"), which have 6 to 10 carbon atoms (a a "C6-C10 alkylene"), which have 1 to 6 carbon atoms (a "C1-C6 alkylene"), 1 to 5 carbon atoms (a "C1-C5 alkylene"), 1 to 4 carbon atoms (a "C6-C10 alkylene"), which have 1 to 6 carbon atoms (a "C1-C6 alkylene"), a "C1-C4 alkylene") or 1 to 3 carbon atoms (a "C1-C3 alkylene"). Examples of alkylene include, but are not limited to, groups such as methylene (-CH2-), ethylene (-CH2CH2-), propylene (-CH2CH2CH2-), isopropylene (-CH2CH(CH3)-), butylene (-CH2(CH2)2CH2 -), isobutylene (-CH2CH(CH3)CH2-), pentylene (-CH2(CH2)3CH2-), hexylene (-CH2(CH2)4CH2-), heptylene (-CH2(CH2)5CH2-), octylene (- CH2(CH2)6CH2-) and the like. It is understood that when alkylene is substituted (for example by a cycloalkyl group), the substituent is not one of the bivalency sites. For example, replacing propylene with cyclopropyl can provide , but does not provide where the wavy line denotes a site of bivalence.

[0033] "Alkenyl", as used herein, refers to and includes, unless otherwise indicated, a linear (i.e., unbranched) or branched univalent hydrocarbon chain or a combination thereof, which has at least one site of olefin unsaturation (i.e., which has at least one chemical moiety of the formula C=C) and which has the designated number of carbon atoms (i.e., C2-C10 means two to ten carbon atoms) . An alkenyl group may have "cis" or "trans" configurations or, alternatively, "E" or "Z" configurations. Particular alkenyl groups are those that have 2 to 20 carbon atoms (a "C2-C20 alkenyl"), which have 6 to 10 carbon atoms (a "C6-C10 alkenyl"), which have 2 to 8 carbon atoms (a "C2-C8 alkenyl"), which have 2 to 6 carbon atoms (a "C2-C6 alkenyl"), or which have 2 to 4 carbon atoms (a "C2-C4 alkenyl"). Examples of alkenyl groups include, but without limitation, groups such as ethenyl (or vinyl), prop-1-enyl, prop-2-enyl (or allyl), 2-methylprop-1-enyl, but-1-enyl, but-2-enyl, but- 3-enyl, buta-1,3-dienyl, 2-methylbuta-1,3-dienyl, pent-1-enyl, pent-2-enyl, hex-1-enyl, hex-2-enyl, hex-3- enila and the like.

[0034] "Alkenylene", as used herein, refers to the same residues as alkenyl, but which have bivalency. Particular alkenylene groups are those that have 2 to 20 carbon atoms (a "C2-C20 alkenylene"), which have 2 to 10 carbon atoms (a "C2-C10 alkenylene"), which have 6 to 10 carbon atoms (a a "C6 C10 alkenylene"), which have 2 to 6 carbon atoms (a "C2-C6 alkenylene"), 2 to 4 carbon atoms (a "C2-C4 alkenylene") or 2 to 3 carbon atoms (a "C2-C3 alkenylene"). Examples of alkenylene include, but are not limited to, groups such as ethenylene (or vinylene) (-CH=CH-), propenylene (-CH=CHCH2-), 1,4-but-1-enylene (-CH=CH-CH2CH2- ), 1,4-but-2-enylene (-CH2CH=CHCH2-), 1,6-hex-1-enylene (-CH=CH-(CH2)3CH2-) and the like.

[0035] "Alkynyl", as used herein, refers to and includes, unless otherwise indicated, an unsaturated (i.e., unbranched) or branched univalent hydrocarbon chain or a combination thereof, which has at least one site of acetylenic unsaturation (i.e., having at least one chemical moiety of the formula C=C) and having the designated number of carbon atoms (i.e., C2-C10 means two to ten carbon atoms). Particular alkynyl groups are those that have 2 to 20 carbon atoms (a "C2-C20 alkynyl"), which have 6 to 10 carbon atoms (a "C6-C10 alkynyl"), which have 2 to 8 carbon atoms (a "C2-C8 alkynyl"), which have 2 to 6 carbon atoms (a "C2-C6 alkynyl"), or which have 2 to 4 carbon atoms (a "C2-C4 alkynyl"). Examples of an alkynyl group include, but are not limited to, groups such as ethynyl (or acetylenyl), prop-1-ynyl, prop-2-ynyl (or propargyl), but-1-ynyl, but-2- inyl, but-3- inila and the like.

[0036] "Alkynylene", as used herein, refers to the same residues as alkynyl, but with bivalency. Particular alkynylene groups are those that have 2 to 20 carbon atoms (a "C2-C20 alkynylene"), which have 2 to 10 carbon atoms (a "C2-C10 alkynylene"), which have 6 to 10 carbon atoms (a a "C6-C10alkynylene"), which have 2 to 6 carbon atoms (a "C2-C6 alkynylene"), 2 to 4 carbon atoms (a "C2-C4 alkynylene"), or 2 to 3 carbon atoms (a "C2-C3 alkynylene"). Examples of alkynylene include, but are not limited to, groups such as ethynylene (or acetynylene) (-C=C-), propynylene (-C=CCH2-) and the like.

[0037] "Cycloalkyl", as used herein, refers to and includes, unless otherwise indicated, univalent saturated cyclic hydrocarbon structures, which have the designated number of carbon atoms (i.e., C3-C10 means three to ten carbon atoms). Cycloalkyl can consist of one ring, such as cyclohexyl, or multiple rings, such as adamantyl. A cycloalkyl comprising more than one ring may be fused, spiro or bridged, or combinations thereof. Particular cycloalkyl groups are those that have 3 to 12 ring carbon atoms. A preferred cycloalkyl is a cyclic hydrocarbon that has 3 to 8 ring carbon atoms (a "C3-C8 cycloalkyl"), that has 3 to 6 ring carbon atoms (a "C3-C6 cycloalkyl"), or that has 3 to 4 ring carbon atoms (a "C3-C4 cycloalkyl"). Examples of cycloalkyl include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, norbornyl and the like.

[0038] "Cycloalkylene", as used herein, refers to the same residues as cycloalkyl, but with bivalency. Cycloalkylene may consist of a ring or multiple rings that may be fused, spiro or bridged, or combinations thereof. Particular cycloalkylene groups are those that have 3 to 12 ring carbon atoms. A preferred cycloalkylene is a cyclic hydrocarbon that has 3 to 8 ring carbon atoms (a "C3-C8 cycloalkylene"), that has 3 to 6 carbon atoms (a "C3-C6 cycloalkylene"), or that has 3 to 4 annular carbon atoms (a "C3-C4 cycloalkylene"). Examples of cycloalkylene include, but are not limited to, cyclopropylene, cyclobutylene, cyclopentylene, cyclohexylene, cycloheptylene, norbornylene and the like. A cycloalkylene can bond to the remaining structures through the same ring carbon atom (e.g., 1,1-cyclopropylene) or different ring carbon atoms (e.g., 1,2-cyclopropylene). When a cycloalkylene bonds to the remaining structures via two different ring carbon atoms, the connecting bonds can be cis or trans to each other (e.g. cis-1,2-cyclopropylene or trans-1,2-cyclopropylene) . If attachment points are not specified, the chemical portion may include any chemically possible bonds. For example, cyclopropylene may indicate 1,1-cyclopropylene or 1,2-cyclopropylene (e.g., cis-1,2-cyclopropylene, trans-1,2-cyclopropylene, or a mixture thereof), or a mixture thereof .

[0039] "Cycloalkenyl" refers to and includes, unless otherwise indicated, an unsaturated cyclic non-aromatic univalent hydrocarbon structure, having at least one site of olefinic unsaturation (i.e., having at least one chemical moiety of the formula C=C) and having the designated number of carbon atoms (i.e., C3-C10 means three to ten carbon atoms). Cycloalkenyl can consist of one ring, such as cyclohexenyl, or multiple rings, such as norbornenyl. A preferred cycloalkenyl is an unsaturated cyclic hydrocarbon having 3 to 8 ring carbon atoms (a "C3-C8 cycloalkenyl"). Examples of cycloalkenyl groups include, but are not limited to, cyclopropenyl, cyclobutenyl, cyclopentenyl, cyclohexenyl, norbornenyl and the like.

[0040] "Cycloalkenylene", as used herein, refers to the same residues as cycloalkenyl, but with bivalence.

[0041] "Aryl" or "Ar", as used herein, refers to an unsaturated aromatic carbocyclic group with a single ring (e.g., phenyl) or multiple condensed rings (e.g., naphthyl or anthryl) whose Condensed rings are carbocyclic and may or may not be aromatic, as long as at least one ring in the condensed ring structure is aromatic. Particular aryl groups are those that have 6 to 14 ring carbon atoms (a "C6-C14 aryl"). An aryl group that has more than one ring where at least one ring is non-aromatic can be connected to the parent structure at an aromatic ring position or at a non-aromatic ring position. In one variation, an aryl group that has more than one ring where at least one ring is non-aromatic is connected to the parent structure at an aromatic ring position.

[0042] "Arylene", as used herein, refers to the same residues as aryl, but with bivalency. Particular arylene groups are those that have 6 to 14 ring carbon atoms (a "C6-C14 arylene").

[0043] "Heteroaryl", as used herein, refers to an unsaturated aromatic cyclic group having from 1 to 14 ring carbon atoms and at least one ring heteroatom, including, but not limited to, heteroatoms, such as nitrogen, oxygen and sulfur. A heteroaryl group may have a single ring (e.g., pyridyl, furyl) or multiple condensed rings (e.g., indolizinyl, benzothienyl) whose condensed rings may be carbocyclic or may contain one or more annular heteroatoms and which may or may not be aromatic, provided that at least one ring in the condensed multiple ring structure is aromatic and contains at least one annular heteroatom. Particular heteroaryl groups are 5- to 14-membered rings having 1 to 12 annular carbon atoms and 1 to 6 annular heteroatoms independently selected from nitrogen, oxygen and sulfur, 5 to 10-membered rings having 1 to 8 annular carbon atoms and 1 to 4 annular heteroatoms selected independently of nitrogen, oxygen and sulfur, or 5-, 6- or 7-membered rings having 1 to 5 annular carbon atoms and 1 to 4 annular heteroatoms selected independently of nitrogen, oxygen and sulfur. In one variation, specific heteroaryl groups are 5-, 6-, or 7-membered monocyclic aromatic rings that have 1 to 6 annular carbon atoms and 1 to 4 annular heteroatoms independently selected from nitrogen, oxygen, and sulfur. In another variation, particular heteroaryl groups are polycyclic aromatic rings that have 1 to 12 annular carbon atoms and 1 to 6 annular heteroatoms independently selected from nitrogen, oxygen and sulfur. A heteroaryl group that has more than one ring in which at least one ring is non-aromatic can be connected to the parent structure at an aromatic ring position or at a non-aromatic ring position. In one variation, a heteroaryl group that has more than one ring in which at least one ring is non-aromatic is connected to the parent structure at an aromatic ring position. A heteroaryl group can be attached to the parent structure at a ring carbon atom or a ring heteroatom.

[0044] "Heteroarylene", as used herein, refers to the same residues as heteroaryl, but with bivalency.

[0045] "Heterocycle", "heterocyclic" or "heterocyclyl", as used herein, refers to a saturated or unsaturated non-aromatic cyclic group that has from 1 to 14 ring carbon atoms and from 1 to 6 ring heteroatoms , such as nitrogen, sulfur or oxygen, and the like. A heterocyclic group may have a single ring (e.g., pyrrolidinyl) or multiple condensed rings (e.g., decahydroisoquinolin-1-yl), which condensed rings may or may not be aromatic and which may be carbocyclic or contain one or more heteroatoms. rings, but which excludes heteroaryl rings. A heterocycle comprising more than one ring may be fused, bridged or spiro, or any combination thereof. In fused ring systems, one or more of the fused rings may be cycloalkyl or aryl, but exclude heteroaryl groups. The heterocyclyl group may optionally be independently substituted by one or more substituents described herein. Particular heterocyclic groups are 3- to 14-membered rings that have 1 to 13 annular carbon atoms and 1 to 6 annular heteroatoms independently selected from nitrogen, oxygen, and sulfur, 3 to 12-membered rings that have 1 to 11 carbon atoms annular and 1 to 6 annular heteroatoms independently selected from nitrogen, oxygen and sulfur, 3 to 10 membered rings having 1 to 9 annular carbon atoms and 1 to 4 annular heteroatoms independently selected from nitrogen, oxygen and sulfur, 3- to 8-membered rings that have 1 to 7 annular carbon atoms and 1 to 4 annular heteroatoms independently selected from nitrogen, oxygen, and sulfur, or 3 to 6-membered rings that have 1 to 5 annular carbon atoms and 1 to 4 annular heteroatoms independently selected from nitrogen, oxygen and sulfur. In one variation, heterocyclyl includes 3-, 4-, 5-, 6-, or 7-membered monocyclic rings that have 1 to 2, 1 to 3, 1 to 4, 1 to 5, or 1 to 6 annular carbon atoms and 1 to 2 , 1 to 3 or 1 to 4 annular heteroatoms independently selected from nitrogen, oxygen and sulfur. In another variation, heterocyclyl includes non-aromatic polycyclic rings having 1 to 12 annular carbon atoms and 1 to 6 annular heteroatoms independently selected from nitrogen, oxygen and sulfur.

[0046] "Heterocyclylene", as used herein, refers to the same residues as heterocyclyl, but with bivalency.

[0047] "Halo" or "halogen" refers to elements of the Group 17 series with atomic numbers from 9 to 85. Preferred halo groups include fluorine, chlorine, bromine and iodine radicals. When a residue is replaced by one or more halogens, it may be referred to using the prefix "halo", e.g. haloaryl, haloalkyl, etc. refer to aryl and alkyl substituted by one or more halo groups, which in the case of two or more halo groups may be, but are not necessarily, the same halogen. When a residue is replaced by more than one halogen, it may be referred to using a prefix corresponding to the number of attached halogen moieties, e.g., dihaloaryl, dihaloalkyl, trihaloaryl, etc. refer to aryl and alkyl substituted by two ("di") or three ("tri") halo groups, which may be but are not necessarily the same halogen; thus, 4-chloro-3-fluorophenyl is within the scope of dihaloaryl. An alkyl group in which each hydrogen is replaced by a halo group is referred to as a "perhaloalkyl". A preferred perhaloalkyl group is trifluoromethyl (-CF3). Likewise, "perhaloalkoxy" refers to an alkoxy group in which a halogen takes the place of each H in the hydrocarbon that constitutes the alkyl chemical portion of the alkoxy group. An example of a perhaloalkoxy group is trifluoromethoxy (-OCF3).

[0048] "Carbonyl" refers to the C=O group.

[0049] "Thiocarbonyl" refers to the C=S group.

[0050] "Oxo" refers to the chemical moiety =O.

[0051] "D" refers to deuterium (2H).

[0052] "Boc" refers to tert-butyloxycarbonyl.

[0053] "Cbz" refers to carboxybenzyl.

[0054] "HATU" refers to 1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium 3-oxide hexafluorophosphate.

[0055] "BOP" refers to benzotriazol-1-yloxytris(dimethylamino)phosphonium hexafluorophosphate.

[0056] "PyBOP" refers to benzotriazol-1-yl-oxytripyrrolidinophosphonium hexafluorophosphate.

[0057] "Optionally substituted", unless otherwise specified, means that a group may be unsubstituted or substituted by one or more (e.g., 1, 2, 3, 4, or 5) of the substituents listed for that group where the substituents can be the same or different. In one embodiment, an optionally substituted group has a substituent. In another embodiment, an optionally substituted group has two substituents. In another embodiment, an optionally substituted group has three substituents. In another embodiment, an optionally substituted group has four substituents. In some embodiments, an optionally substituted group has 1 to 2, 1 to 3, 1 to 4, 1 to 5, 2 to 3, 2 to 4, or 2 to 5 substituents. In one embodiment, an optionally substituted group is unsubstituted.

[0058] Unless clearly indicated otherwise, "an individual", as used herein, refers to a mammal, including, but not limited to, a primate, human, bovine, horse, feline, canine or rodent. In one variation, the individual is a human being.

[0059] As used herein, "treatment" or "treat" is an approach to obtaining beneficial or desired results, including clinical results. For purposes of this invention, beneficial or desired results include, but are not limited to, one or more of the following: further decreasing one of the symptoms resulting from the disease, decreasing the extent of the disease, stabilizing the disease (e.g., preventing or delaying worsening of the disease), prevent or delay the spread of the disease, delay the occurrence or recurrence of the disease, delay or reduce the progression of the disease, improve the state of the disease, provide a remission (whether partial or complete) of the disease, decrease the dose of one or more other medications necessary to treat the disease, enhance the effect of another medication, slow the progression of the disease, increase quality of life and/or prolong survival. Also encompassed by "treatment" is the reduction of the pathological consequences of fibrosis. The methods of the invention contemplate any one or more of these aspects of treatment.

[0060] As used herein, the term "effective amount" means such an amount of a compound of the invention that should be effective in a given therapeutic form. As is understood in the art, an effective amount may be in one or more doses, that is, a single dose or multiple doses may be necessary to achieve the desired treatment endpoint. An effective amount may be considered in the context of administering one or more therapeutic agents (e.g., a compound, or a pharmaceutically acceptable salt thereof), and a single agent may be considered to be given in an effective amount if, together with one or more other agents, a desirable or beneficial result can be or is achieved. Suitable doses of any of the co-administered compounds may be optionally reduced due to the combined action (e.g., additive or synergistic effects) of the compounds.

[0061] A "therapeutically effective amount" refers to an amount of a compound or salt thereof sufficient to produce a desired therapeutic result.

[0062] As used herein, "unit dosage form" refers to physically discrete units, suitable as unitary dosages, each unit containing a predetermined quantity of active ingredient calculated to produce the desired therapeutic effect in association with the required pharmaceutical carrier. . Unit dosage forms may contain single or combination therapy.

[0063] As used herein, the term "controlled release" refers to a formulation containing drug or fraction thereof in which the release of the drug is not immediate, that is, with a "controlled release" formulation, administration does not result in immediate release of the drug into an absorption pool. The term encompasses depot formulations designed to gradually release the drug compound over an extended period of time. Controlled-release formulations can include a wide variety of drug delivery systems, generally involving mixing the drug compound with carriers, polymers, or other compounds with desired release characteristics (e.g., pH-dependent or non-pH-dependent solubility, different degrees of solubility in water and the like) and formulating the mixture according to the desired delivery route (for example, coated capsules, implantable reservoirs, injectable solutions containing biodegradable capsules and the like).

[0064] As used herein, by "pharmaceutically acceptable" or "pharmacologically acceptable" means a material that is not biologically or otherwise undesirable, for example, the material can be incorporated into a pharmaceutical composition administered to a patient without causing any significant undesirable biological effects or interact harmfully with any of the other components of the composition in which it is contained. Pharmaceutically acceptable carriers or excipients have preferably met the required manufacturing and toxicological testing standards and/or are included in the Inactive Ingredients Guide prepared by the US Food and Drug Administration.

[0065] "Pharmaceutically acceptable salts" are those salts that retain at least part of the biological activity of the free compound (non-salt) and that can be administered as drugs or pharmaceutical products to an individual. Such salts, for example, include: (1) acid addition salts, formed with inorganic acids, such as hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid and the like; or formed with organic acids such as acetic acid, oxalic acid, propionic acid, succinic acid, maleic acid, tartaric acid and the like; (2) salts formed when an acidic proton present in the parent compound is replaced by a metal ion, for example, an alkali metal ion, an alkaline earth ion, or an aluminum ion; or coordinates with an organic base. Acceptable organic bases include ethanolamine, diethanolamine, triethanolamine and the like. Acceptable inorganic bases include aluminum hydroxide, calcium hydroxide, potassium hydroxide, sodium carbonate, sodium hydroxide and the like. Pharmaceutically acceptable salts may be prepared in situ in the manufacturing process, or by separately reacting a purified compound of the invention in its free acid or base form with a suitable organic or inorganic base or acid, respectively, and isolating the salt so formed. during purification.

[0066] The term "excipient" as used herein means an inert or inactive substance that can be used in the production of a drug or pharmaceutical product, such as a tablet that contains a compound of the invention as an active ingredient. Various substances may be covered by the term excipient, including, without limitation, any substance used as a binder, disintegrant, coating, compression/encapsulation aid, cream or lotion, lubricant, solutions for parenteral administration, materials for chewable tablets, sweetener or flavoring, suspension/gelling agent or wet granulating agent. Binders include, for example, carbomers, povidone, xanthan gum, etc.; coatings include, for example, cellulose acetate phthalate, ethyl cellulose, gel gum, maltodextrin, enteric coatings, etc.; compression/encapsulation aids include, for example, calcium carbonate, dextrose, fructose dc (dc = "directly compressible"), honey dc, lactose (anhydrate or monohydrate; optionally in combination with aspartame, cellulose or microcrystalline cellulose), dc starch, sucrose etc.; disintegrants include, for example, croscarmellose sodium, gellan gum, sodium starch glycolate, etc.; creams or lotions include, for example, maltodextrin, carrageenans, etc.; lubricants include, for example, magnesium stearate, stearic acid, sodium stearyl fumarate, etc.; materials for chewable tablets include, for example, dextrose, fructose dc, lactose (monohydrate, optionally in combination with aspartame or cellulose), etc.; suspending/gelling agents include, for example, carrageenan, sodium starch glycolate, xanthan gum, etc.; sweeteners include, for example, aspartame, dextrose, fructose dc, sorbitol, sucrose dc, etc.; and wet granulating agents include, for example, calcium carbonate, maltodextrin, microcrystalline cellulose, etc.

[0067] Unless otherwise indicated, "substantially pure" means a composition that does not contain more than 10% impurity, such as a composition that comprises less than 9%, 7%, 5%, 3%, 1% , 0.5% impurity.

[0068] It is understood that aspects and modalities described herein as "comprising" include modalities "consisting of" and "consisting essentially of".

[0069] When a composition is described as "consisting essentially of" the listed components, the composition contains the expressly listed components and may contain other components that do not substantially affect the disease or condition being treated, such as traces of impurities. However, the composition either does not contain any other components that substantially affect the disease or condition being treated in addition to the expressly listed components; or, if the composition contains extra components other than those listed that substantially affect the disease or condition being treated, the composition does not contain a sufficient concentration or quantity of these extra components to substantially affect the disease or condition being treated. When a method is described as "consisting essentially of" the listed steps, the method contains the listed steps and may contain other steps that do not substantially affect the disease or condition being treated, but the method does not contain any other steps that substantially affect the disease or condition to be treated beyond the steps expressly listed.

COMPOUNDS

[0070] In one aspect, a compound of formula (I) is provided:

[0071] or a salt thereof, wherein:

[0072] R1 is 5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl optionally substituted by R4, 1,2,3,4-tetrahydro-1,8-naphthyridin-2- yyl optionally substituted by R4, 6-aminopyridin-2-yl optionally substituted by R4, or (pyridin-2-yl)amino optionally substituted by R4;

[0073] G is -C(O)R2or R3;

[0074] R2 is C1-C6 alkyl optionally substituted by R2a, C3-C8 cycloalkyl optionally substituted by R2b, 3- to 12-membered heterocyclyl optionally substituted by R2c, C6-C14 aryl optionally substituted by R2d, 5- to 10-membered heteroaryl optionally substituted by R2e, -OR2for -NR2gR2h;

[0075] R3 is C1-C6 alkyl optionally substituted by R3a, C3-C8 cycloalkyl optionally substituted by R3b, 3- to 12-membered heterocyclyl optionally substituted by R3c, C6-C14 aryl optionally substituted by R3, or 5- to 10-membered heteroaryl optionally substituted by R3e;

[0076] L1 is C2-C4 alkylene optionally substituted by R4;

[0077] L2 is a bond or C1-C3 alkylene optionally substituted by R4;

[0078] L3 is C2-C4 alkylene optionally substituted by R4;

[0079] Y is a bond or C3-C5 cycloalkylene optionally substituted by Ya;

[0080] R2 is C1-C6 alkyl, C3-C8 cycloalkyl, 3- to 12-membered heterocyclyl, C6-C14 aryl or 5- to 10-membered heteroaryl, wherein C1 C6 alkyl, C3-C8 cycloalkyl, 3 to 12 heterocyclyl members, C6-C14 aryl and heteroaryl of 5 to 10 members of R2f are optionally independently substituted by R2i;

[0081] R2g and R2h are, each independently, hydrogen, deuterium, C1-C6 alkyl, C3-C8 cycloalkyl, 3- to 12-membered heterocyclyl, C6-C14 aryl or 5- to 10-membered heteroaryl, wherein C1 C6 alkyl, C3-C8 cycloalkyl, 3- to 12-membered heterocyclyl, C6-C14 aryl and 5- to 10-membered heteroaryl of R2g and R2h are optionally independently substituted by R2j;

[0082] each R2a, R2b, R2c, R2d, R2e, R2i, R2j, R3a, R3b, R3c, R3d, R3ee Ya is independently oxo or R4;

[0083] each R4 is independently deuterium, halogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C8 cycloalkyl, 3- to 12-membered heterocyclyl, C6-C14 aryl, 5- to 10-membered heteroaryl, - CN, -OR5, - SR5, -NR6R7, -NO2, -C=NH(OR5), -C(O)R5, -OC(O)R5, -C(O)OR5, -C(O) NR6R7, -NR5C(O)R6, -NR5C(O)OR6, -NR5C(O)NR6R7, -S(O)R5, -S(O)2R 5, -NR5S(O)R6, -NR5S(O)2R6, -S(O)NR6R7, -S(O)2NR6R7 or -P(O)(OR5)(OR6), where C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C8 cycloalkyl, heterocyclyl 3 to 12 membered, C6-C14 aryl, 5 to 10 membered heteroaryl of R4 are optionally independently substituted by R4a;

[0084] each R4a is independently deuterium, halogen, oxo, -OR8, -NR8R9, -C(O)R8, C(O)OR8, -NR8C(O)OR10, -CN, -S(O)R8, -S (O)2R8, -P(O)(OR8)(OR9), C3 C8 cycloalkyl, 3- to 12-membered heterocyclyl, 5- to 10-membered heteroaryl, C6-C14 aryl or C1-C6 alkyl, wherein the heterocyclyl of 3 to 12 membered, 5 to 10 membered heteroaryl, C6-C14 aryl and C1-C6 alkyl of R4asion, independently, optionally substituted by R4b;

[0085] each R4 is independently deuterium, oxo, -OH, -O(2H), halogen or C1-C6 alkyl optionally substituted by deuterium, halogen, -OH, -O(2H) or oxo;

[0086] each R5 is independently hydrogen, deuterium, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C6-C14 aryl, 5- to 10-membered heteroaryl, or 3- to 10-membered heterocyclyl, wherein the C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C6-C14 aryl, 5- to 10-membered heteroaryl, and 3- to 10-membered heterocyclyl of R5 are each substituted by optionally independent mode by R5a;

[0087] each R5a is independently halogen, deuterium, oxo, -CN, -OR10, -NR11R12, -P(O)(OR11)(OR12), 3- to 12-membered heterocyclyl, or C1-C6 alkyl optionally substituted by deuterium, halogen, -OH, -O(2H) or oxo;

[0088] each R6 is independently hydrogen, deuterium, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C6-C14 aryl, 5- to 10-membered heteroaryl, or 3- to 6-membered heterocyclyl, wherein the C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C6-C14 aryl, 5- to 10-membered heteroaryl, and 3- to 6-membered heterocyclyl of R6 are optionally independently substituted by deuterium, halogen, oxo, -CN, -OR10, -NR11R12, or C1-C6 alkyl optionally substituted by deuterium, halogen, -OH, -O(2H) or oxo;

[0089] each R7 is independently hydrogen, deuterium, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C6-C14 aryl, 5- to 10-membered heteroaryl, or 3- to 6-membered heterocyclyl, wherein the C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C6-C14 aryl, 5- to 10-membered heteroaryl, and 3- to 6-membered heterocyclyl of R7 are optionally independently substituted by deuterium, halogen, oxo, -CN, -OR10, -NR11R12, or C1-C6 alkyl optionally substituted by deuterium, halogen, -OH, -O(2H) or oxo;

[0090] or R6 and R7 are taken together with the atom to which they are bonded to form a 3 to 10 membered heterocyclyl optionally substituted by deuterium, halogen, oxo -OR10, -NR11R12 or C1-C6 alkyl optionally substituted by deuterium, halogen, oxo, -OH or -O(2H);

[0091] each R8 is independently hydrogen, deuterium, C1-C6 alkyl optionally substituted by deuterium, halogen or oxo, C2-C6 alkenyl optionally substituted by deuterium, halogen or oxo, or C2-C6 alkynyl optionally substituted by deuterium, halogen or oxo;

[0092] each R9 is independently hydrogen, deuterium, C1-C6 alkyl optionally substituted by deuterium, halogen or oxo, C2-C6 alkenyl optionally substituted by deuterium, halogen or oxo, or C2-C6 alkynyl optionally substituted by deuterium, halogen or oxo;

[0093] each R10 is independently hydrogen, deuterium, C1-C6 alkyl optionally substituted by deuterium, halogen or oxo, C2-C6 alkenyl optionally substituted by deuterium, halogen or oxo, or C2-C6 alkynyl optionally substituted by deuterium, halogen or oxo;

[0094] each R11 is independently hydrogen, deuterium, C1-C6 alkyl optionally substituted by deuterium, halogen or oxo, C2-C6 alkenyl optionally substituted by deuterium, halogen or oxo, or C2-C6 alkynyl optionally substituted by deuterium, halogen or oxo; It is

[0095] each R12 is independently hydrogen, deuterium, C1-C6 alkyl optionally substituted by deuterium, halogen or oxo, C2-C6 alkenyl optionally substituted by deuterium, halogen or oxo, or C2-C6 alkynyl optionally substituted by deuterium, halogen or oxo;

[0096] or R11 and R12 are taken together with the atom to which they are bonded to form a 3 to 6 membered heterocyclyl optionally substituted by deuterium, halogen, oxo or C1-C6 alkyl optionally substituted by deuterium, oxo or halogen.

[0097] In one variation, a compound of formula (I), or a salt thereof, is provided, in which the carbon carrying the chemical moieties CO2H and N(H)G is in the "S" configuration. In another variation, a compound of formula (I), or a salt thereof, is provided, in which the carbon carrying the chemical moieties CO2H and N(H)G is in the "R" configuration. Mixtures of a compound of formula (I) are also covered, including racemic or non-racemic mixtures of a given compound and mixtures of two or more compounds of different chemical formulas.

[0098] In the descriptions herein, it is understood that each description, variation, modality or aspect of a chemical moiety may be combined with each description, variation, modality or aspect of other chemical moieties in the same way as if each combination of descriptions was specifically and individually listed. For example, each description, variation, embodiment or aspect provided herein with respect to G of formula (I) may be combined with each description, variation, embodiment or aspect of L1, L2, Y, L2 and/or R1 in the same manner as if each combination were specifically and individually listed. It is also understood that all descriptions, variations, embodiments or aspects of formula (I), where applicable, apply equally to other formulas detailed in this document, and are equally described, in the same manner as if each and every description, variation, embodiment or aspect was listed separately and individually for all formulas. For example, all descriptions, variations, embodiments or aspects of formula (I), where applicable, apply equally to any of formulas (IIa), (IIb), (IIIa), (IIIb), (IVa), ( IVb), (Va), (Va-1), (Va-2), (Vb), (Vb-1) and (Vb-2) detailed in this document, and are equally described, in the same way as if each description , variation, modality or aspect was listed separately and individually for all formulas.

[0099] In some embodiments of the compound of formula (I), or a salt thereof, L1 is C2-C4 alkylene. In a particular variation, L1 is -CH2-CH2-, -CH2-CH2-CH2-, or -CH2-CH2-CH2-CH2-. In another variation, L1 is -CH2-CH2-.

[0100] In some embodiments of the compound of formula (I), or a salt thereof, -L2- is a bond.

[0101] In some embodiments of the compound of formula (I), or a salt thereof, -Y- is a bond.

[0102] In some embodiments of the compound of formula (I), or a salt thereof, -Y- is C3-C4 cycloalkylene. In one aspect, Y is a C3 cycloalkylene. In another aspect, Y is C4 cycloalkylene. In one variation, the point of attachment of the C3-C4 cycloalkylene to L2 and L3 is via the same carbon atom (e.g. variation, the point of attachment of C3-C4 cycloalkylene to L2 and L3 is through two different carbon atoms (e.g. . In another variation, when the point of attachment of the C3-C4 cycloalkylene to L2 and L3 is through two different carbon atoms, the stereochemistry introduced into the C3-C4 cycloalkylene is trans In another variation, when the point of attachment of the C3-C4 cycloalkylene to L2 and L3 is through two different carbon atoms, the stereochemistry introduced into the C3-C4 cycloalkylene is cis (e.g.

[0103] In some embodiments of the compound of formula (I), or a salt thereof, at least one of R2g, R2h, R4, R4a, R4b, R5, R5a, R6, R7, R8, R9, R10, R11or R12é deuterium.

[0104] In some embodiments of the compound of formula (I), or a salt thereof, -L2-Y-L3- are taken together to form a chemical moiety selected from the group consisting of: -CH2CH2CH2-, - CH2(CH2)2CH2-, -CH2(CH2)3CH2-, ; where the wavy lines denote attachment points to the original molecule.

[0105] In some embodiments of the compound of formula (I), or a salt thereof, -L1-O-L2-Y-L3- are taken together to form a chemical moiety selected from the group consisting of:

[0106] where is the C3-C5 cycloalkylene optionally substituted by Ya, and

[0107] where és is the C3-C5 cycloalkylene optionally substituted by Ya.

[0108] In some embodiments of the compound of formula (I), or a salt thereof, -L1-O-L2-Y-L3- are taken together to form a chemical moiety selected from the group consisting of: In another variation, -L1-O-L2-Y-L3- are taken together to form a chemical moiety selected from the group consisting of: another particular variation, -L1-O-L2-Y-L3- are taken together to form a chemical moiety selected from the group consisting of

[0109] In one embodiment, the compound of formula (I) or a salt thereof is provided, wherein: R1 is 1,2,3,4-tetrahydro-1,8-naphthyridin-2-yl; L1 is -CH2CH2-, Y is a bond, and L3 is -CH2CH2CH2CH2-; and G is - C(O)R2, wherein R2 is a six-membered heterocyclyl, aryl or heterocyclyl ring, wherein among the substitutable ring atoms in R2, 1 saturated ring atom, or 2 or 3 unsaturated ring atoms are independently substituted by halogen, C1-C6 alkyl or C1-C6 haloalkyl. In one embodiment, the compound of formula (I) or a salt thereof is provided, wherein: R1 is 1,2,3,4-tetrahydro-1,8-naphthyridin-2-yl; L1 is -CH2CH2CH2-, Y is a bond, and L3 is -CH2CH2CH2-; and G is - C(O)R2, wherein R2 is a six-membered heterocyclyl, aryl or heterocyclyl ring, wherein among the substitutable ring atoms in R2, 1 saturated ring atom, or 2 or 3 unsaturated ring atoms are independently substituted by halogen, C1-C6 alkyl or C1-C6 haloalkyl. In one embodiment, the compound of formula (I) or a salt thereof is provided, wherein: R1 is 1,2,3,4-tetrahydro-1,8-naphthyridin-2-yl; L1 is -CH2CH2CH2CH2-, Y is a bond, and L3 is -CH2CH2-; and G is - C(O)R2, wherein R2 is a six-membered heterocyclyl, aryl or heterocyclyl ring, wherein among the substitutable ring atoms in R2, 1 saturated ring atom, or 2 or 3 unsaturated ring atoms are independently substituted by halogen, C1-C6 alkyl or C1-C6 haloalkyl. In one embodiment, the compound of formula (I) or a salt thereof is provided, wherein: R1 is 1,2,3,4-tetrahydro-1,8-naphthyridin-2-yl; L1 is -CH2CH2-, Y is 1,3-cyclobutyl, and L3 is -CH2CH2-; and G is -C(O)R2, wherein R2 is a six-membered heterocyclyl, aryl or heterocyclyl ring, wherein among the substitutable ring atoms in R2, 1 saturated ring atom, or 2 or 3 unsaturated ring atoms are independently substituted by halogen, C1-C6 alkyl or C1-C6 haloalkyl. In one embodiment, the compound of formula (I) or a salt thereof is provided, wherein: R1 is 1,2,3,4-tetrahydro-1,8-naphthyridin-2-yl; L1 is -CH2CH2-, Y is cis-1,3-cyclobutyl, and L3 is -CH2CH2-; and G is - C(O)R2, wherein R2 is a six-membered heterocyclyl, aryl or heterocyclyl ring, wherein among the substitutable ring atoms in R2, 1 saturated ring atom, or 2 or 3 unsaturated ring atoms are independently substituted by halogen, C1-C6 alkyl or C1-C6 haloalkyl. In one embodiment, the compound of formula (I) or a salt thereof is provided, wherein: R1 is 1,2,3,4-tetrahydro-1,8-naphthyridin-2-yl; L1 is -CH2CH2-, Y is trans-1,3-cyclobutyl, and L3 is -CH2CH2-; and G is - C(O)R2, wherein R2 is a six-membered heterocyclyl, aryl or heterocyclyl ring, wherein among the substitutable ring atoms in R2, 1 saturated ring atom, or 2 or 3 unsaturated ring atoms are independently substituted by halogen, C1-C6 alkyl or C1-C6 haloalkyl. In one embodiment, the compound of formula (I) or a salt thereof is provided, wherein: R1 is 1,2,3,4-tetrahydro-1,8-naphthyridin-2-yl; L1 is -CH2CH2-, Y is a bond, and L3 is -CH2CH2CH2CH2-; and G is - R3, wherein R3 is a six-membered heterocyclyl, aryl or heterocyclyl ring, wherein among the substitutable ring atoms in R2, 1 saturated ring atom, or 2 or 3 unsaturated ring atoms are independently substituted by halogen, C1-C6 alkyl or C1-C6 haloalkyl. In one embodiment, the compound of formula (I) or a salt thereof is provided, wherein: R1 is 1,2,3,4-tetrahydro-1,8-naphthyridin-2-yl; L1 is -CH2CH2CH2-, Y is a bond, and L3 is -CH2CH2CH2-; and G is - R3, wherein R3 is a six-membered heterocyclyl, aryl or heterocyclyl ring, wherein among the substitutable ring atoms in R2, 1 saturated ring atom, or 2 or 3 unsaturated ring atoms are independently substituted by halogen, C1-C6 alkyl or C1-C6 haloalkyl. In one embodiment, the compound of formula (I) or a salt thereof is provided, wherein: R1 is 1,2,3,4-tetrahydro-1,8-naphthyridin-2-yl; L1 is -CH2CH2CH2CH2-, Y is a bond, and L3 is -CH2CH2-; and G is - R3, wherein R3 is a six-membered heterocyclyl, aryl or heterocyclyl ring, wherein among the substitutable ring atoms in R2, 1 saturated ring atom, or 2 or 3 unsaturated ring atoms are independently substituted by halogen, C1-C6 alkyl or C1-C6 haloalkyl. In one embodiment, the compound of formula (I) or a salt thereof is provided, wherein: R1 is 1,2,3,4-tetrahydro-1,8-naphthyridin-2-yl; L1 is -CH2CH2-, Y is 1,3-cyclobutyl, and L3 is -CH2CH2-; and G is -R3, wherein R3 is a six-membered heterocyclyl, aryl or heterocyclyl ring, wherein among the substitutable ring atoms in R2, 1 saturated ring atom, or 2 or 3 unsaturated ring atoms are independently substituted by halogen, C1-C6 alkyl or C1-C6 haloalkyl. In one embodiment, the compound of formula (I) or a salt thereof is provided, wherein: R1 is 1,2,3,4-tetrahydro-1,8-naphthyridin-2-yl; L1 is -CH2CH2-, Y is cis-1,3-cyclobutyl, and L3 is -CH2CH2-; and G is -R3, wherein R3 is a six-membered heterocyclyl, aryl or heterocyclyl ring, wherein among the substitutable ring atoms in R2, 1 saturated ring atom, or 2 or 3 unsaturated ring atoms are independently substituted by halogen, C1-C6 alkyl or C1-C6 haloalkyl. In one embodiment, the compound of formula (I) or a salt thereof is provided, wherein: R1 is 1,2,3,4-tetrahydro-1,8-naphthyridin-2-yl; L1 is -CH2CH2-, Y is trans-1,3-cyclobutyl, and L3 is -CH2CH2-; and G is -R3, wherein R3 is a six-membered heterocyclyl, aryl or heterocyclyl ring, wherein among the substitutable ring atoms in R2, 1 saturated ring atom, or 2 or 3 unsaturated ring atoms are independently substituted by halogen, C1-C6 alkyl or C1-C6 haloalkyl. For each individual prior embodiment described in this paragraph, an additional embodiment is disclosed in which among the substitutable ring atoms in R2, one of: a saturated ring atom is substituted by C1-C6 haloalkyl, for example, -CF3; two aryl ring atoms are independently substituted by halogen; and 2 or 3 atoms of the heteroaryl ring are independently substituted by halogen or C1-C6 alkyl, e.g. methyl. Furthermore, in various embodiments, each previous embodiment described in this paragraph may be excluded from the compound represented by formula (I) and salts thereof.

[0110] In one embodiment, the compound of formula (I) or a salt thereof is provided in which: R1 is 5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl; L1 is -CH2CH2-, Y is a bond, and L3 is -CH2CH2CH2CH2-; and G is - C(O)R2, wherein R2 is a six-membered heterocyclyl, aryl or heteroaryl ring, wherein among the substitutable ring atoms in R2, 1 saturated ring atom, or 2 or 3 unsaturated ring atoms are independently substituted by halogen, C1-C6 alkyl or C1-C6 haloalkyl. In one embodiment, the compound of formula (I) or a salt thereof is provided in which: R1 is 5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl; L1 is -CH2CH2CH2-, Y is a bond, and L3 is -CH2CH2CH2-; and G is - C(O)R2, wherein R2 is a six-membered heterocyclyl, aryl or heteroaryl ring, wherein among the substitutable ring atoms in R2, 1 saturated ring atom, or 2 or 3 unsaturated ring atoms are independently substituted by halogen, C1-C6 alkyl or C1-C6 haloalkyl. In one embodiment, the compound of formula (I) or a salt thereof is provided in which: R1 is 5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl; L1 is -CH2CH2CH2CH2-, Y is a bond, and L3 is -CH2CH2-; and G is - C(O)R2, wherein R2 is a six-membered heterocyclyl, aryl or heteroaryl ring, wherein among the substitutable ring atoms in R2, 1 saturated ring atom, or 2 or 3 unsaturated ring atoms are independently substituted by halogen, C1-C6 alkyl or C1-C6 haloalkyl. In one embodiment, the compound of formula (I) or a salt thereof is provided in which: R1 is 5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl; L1 is -CH2CH2-, Y is 1,3-cyclobutyl, and L3 is -CH2CH2-; and G is -C(O)R2, wherein R2 is a six-membered heterocyclyl, aryl or heteroaryl ring, wherein among the substitutable ring atoms in R2, 1 saturated ring atom, or 2 or 3 unsaturated ring atoms are independently substituted by halogen, C1-C6 alkyl or C1-C6 haloalkyl. In one embodiment, the compound of formula (I) or a salt thereof is provided in which: R1 is 5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl; L1 is -CH2CH2-, Y is cis -1,3-cyclobutyl, and L3 is -CH2CH2-; and G is -C(O)R2, wherein R2 is a six-membered heterocyclyl, aryl or heteroaryl ring, wherein among the substitutable ring atoms in R2, 1 saturated ring atom, or 2 or 3 unsaturated ring atoms are independently substituted by halogen, C1-C6 alkyl or C1-C6 haloalkyl. In one embodiment, the compound of formula (I) or a salt thereof is provided in which: R1 is 5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl; L1 is -CH2CH2-, Y is trans -1,3-cyclobutyl, and L3 is -CH2CH2-; and G is -C(O)R2, wherein R2 is a six-membered heterocyclyl, aryl or heteroaryl ring, wherein among the substitutable ring atoms in R2, 1 saturated ring atom, or 2 or 3 unsaturated ring atoms are independently substituted by halogen, C1-C6 alkyl or C1-C6 haloalkyl. In one embodiment, the compound of formula (I) or a salt thereof is provided in which: R1 is 5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl; L1 is -CH2CH2-, Y is a bond, and L3 is -CH2CH2CH2CH2-; and G is -R3, wherein R3 is a six-membered heterocyclyl, aryl or heteroaryl ring, wherein among the substitutable ring atoms in R2, 1 saturated ring atom, or 2 or 3 unsaturated ring atoms are independently substituted by halogen, C1-C6 alkyl or C1-C6 haloalkyl. In one embodiment, the compound of formula (I) or a salt thereof is provided in which: R1 is 5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl; L1 is -CH2CH2CH2-, Y is a bond, and L3 is -CH2CH2CH2-; and G is -R3, wherein R3 is a six-membered heterocyclyl, aryl or heteroaryl ring, wherein among the substitutable ring atoms in R2, 1 saturated ring atom, or 2 or 3 unsaturated ring atoms are independently substituted by halogen, C1-C6 alkyl or C1-C6 haloalkyl. In one embodiment, the compound of formula (I) or a salt thereof is provided in which: R1 is 5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl; L1 is -CH2CH2CH2CH2-, Y is a bond, and L3 is -CH2CH2-; and G is -R3, wherein R3 is a six-membered heterocyclyl, aryl or heteroaryl ring, wherein among the substitutable ring atoms in R2, 1 saturated ring atom, or 2 or 3 unsaturated ring atoms are independently substituted by halogen, C1-C6 alkyl or C1-C6 haloalkyl. In one embodiment, the compound of formula (I) or a salt thereof is provided in which: R1 is 5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl; L1 is -CH2CH2-, Y is 1,3-cyclobutyl, and L3 is -CH2CH2-; and G is -R3, wherein R3 is a six-membered heterocyclyl, aryl or heteroaryl ring, wherein among the substitutable ring atoms in R2, 1 saturated ring atom, or 2 or 3 unsaturated ring atoms are independently substituted by halogen, C1-C6 alkyl or C1-C6 haloalkyl. In one embodiment, the compound of formula (I) or a salt thereof is provided in which: R1 is 5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl; L1 is -CH2CH2-, Y is cis-1,3-cyclobutyl, and L3 is -CH2CH2-; and G is —R3, wherein R3 is a six-membered heterocyclyl, aryl or heteroaryl ring, wherein among the substitutable ring atoms in R2, 1 saturated ring atom, or 2 or 3 unsaturated ring atoms are independently substituted by halogen, C1-C6 alkyl or C1-C6 haloalkyl. In one embodiment, the compound of formula (I) or a salt thereof is provided in which: R1 is 5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl; L1 is -CH2CH2-, Y is trans-1,3-cyclobutyl, and L3 is -CH2CH2-; and G is -R3, wherein R3 is a six-membered heterocyclyl, aryl or heteroaryl ring, wherein among the substitutable ring atoms in R2, 1 saturated ring atom, or 2 or 3 unsaturated ring atoms are independently substituted by halogen, C1-C6 alkyl or C1-C6 haloalkyl. For each individual prior embodiment described in this paragraph, an additional embodiment is disclosed in which among the substitutable ring atoms in R2, one of: a saturated ring atom is substituted by C1-C6 haloalkyl, for example, -CF3; two aryl ring atoms are independently substituted by halogen; and 2 or 3 atoms of the heteroaryl ring are independently substituted by halogen or C1-C6 alkyl, e.g. methyl. Furthermore, in various embodiments, each previous embodiment described in this paragraph may be excluded from the compound represented by formula (I) and salts thereof.

[0111] In some embodiments, the compound of formula (I) has formula (IIa):

[0112] or a salt thereof, wherein R2 is as defined for formula (I).

[0113] In some embodiments, the compound of formula (I) has formula (IIb):

[0114] or a salt thereof, wherein R3 is as defined for formula (I).

[0115] In some embodiments, the compound of formula (I) has formula (IIIa):

[0116] or a salt thereof, wherein R2 is as defined for formula (I).

[0117] In some embodiments, the compound of formula (I) has formula (IIIb):

[0118] or a salt thereof, wherein R3 is as defined for formula (l).

[0119] In some embodiments, the compound of formula (l) has the formula (lVa):

[0120] or a salt thereof, wherein R2 is as defined for formula (l).

[0121] In some embodiments, the compound of formula (l) has the formula (lVb):

[0122] or a salt thereof, wherein R3 is as defined for formula (l).

[0123] In some embodiments, the compound of formula (l) has the formula (Va):

[0124] or a salt thereof, wherein R2 is as defined for formula (I).

[0125] In some embodiments, the compound of formula (Va) has the formula (Va-1):

[0126] or a salt thereof, wherein R2 is as defined for formula (I).

[0127] In some embodiments, the compound of formula (Va) has the formula (Va-2):

[0128] or a salt thereof, wherein R2 is as defined for formula (I).

[0129] In some embodiments, the compound of formula (I) has formula (Vb):

[0130] or a salt thereof, wherein R3 is as defined for formula (I).

[0131] In some embodiments, the compound of formula (Vb) has the formula (Vb-1):

[0132] or a salt thereof, wherein R3 is as defined for formula (I).

[0133] In some embodiments, the compound of formula (Vb) has the formula (Vb-2):

[0134] or a salt thereof, wherein R3 is as defined for formula (I).

[0135] In some embodiments, the compound of formula (I) has the formula:

[0136] where j and k are, respectively, 2 and 4, 3 and 3 or 4 and 2,

[0137] or a salt thereof.

[0138] In some embodiments, the compound of formula (I) has the formula

[0139] or a salt thereof.

[0140] In some embodiments, the compound of formula (I) has the formula:

[0141] or a salt thereof.

[0142] In some embodiments, the compound of formula (I) has the formula:

[0143] or a salt thereof.

[0144] In some embodiments, the compound of formula (I) has the formula:

[0145] or a salt thereof.

[0146] In some embodiments, the compound of formula (I) has the formula:

[0147] or a salt thereof.

[0148] In some embodiments, the compound of formula (I) has the formula:

[0149] or a salt thereof.

[0150] In some embodiments, the compound of formula (I) has the formula:

[0151] or a salt thereof.

[0152] In some embodiments, the compound of formula (I) has the formula:

[0153] or a salt thereof.

[0154] In some embodiments, the compound of formula (I) has the formula:

[0155] or a salt thereof.

[0156] In some embodiments, the compound of formula (I) has the formula:

[0157] or a salt thereof.

[0158] In some embodiments, the compound of formula (I) has the formula:

[0159] where j and k are, respectively, 2 and 4, 3 and 3 or 4 and 2,

[0160] or a salt thereof.

[0161] In some embodiments, the compound of formula (I) has the formula: or a salt thereof.

[0162] In some embodiments, the compound of formula (I) has the formula:

[0163] or a salt thereof.

[0164] Reference to formula (I) or any variation thereof includes reference to (IIa), (IIb), (IIIa), (IIIb), (IVa), (IVb), (Va), (Va- 1), (Va- 2), (Vb), (Vb-1), (Vb-2), (II-A-1), (II-A-2), (II-A-2i), ( II-A-2ii), (II-A-1a-1), (II-A-1a-2), (II-A-1a-3), (II-A-1b-1), (II- A-1b-2), (II-A-1c-1), (II-A-1c-2), (II- A-1d-1), (II-A-1d-2), (II- A-1d-3), (II-A-2a-1), (II-A-2a-2), (II-A-2a-3), (II-A- 2a-4), (II- A-2b-1), (II-A-2b-2), (II-A-2c-1), (II-A-2c-2), (II-A-2c-3), (II- A-2c- 4), (II-A-2d-1), (II-A-2d-2), (II-A-2d-3), (II-A-2d-4), (II- A-2d-5), (II-A-2d-6), (II-A-2e-1), (II-A-2e-2), (II-A-2e-3), (II- A-2e-4), (II-A-2e-5), (II-A-2e-6), (II- A-2e-7), (II-A-2e-8), (II- A-2f-1), (II-A-2f-2), (II-A-2f-3), (II-A-2f-4), (II-A-2f- 5), (II- A-2f-6), (II-A-2f-7), (II-A-2f-8), (II-A-2f-9), (II-A-2f-10), (II- B-1), (II- B-2), (II-B-3), (II-B-1a), (II-B-2a), (II-B-2b), (II-B- 3a) or (II-B-3b), a compound of Table 1 or Table 2, or any of compounds 1 to 329.

[0165] In some embodiments of the compound of formula (I), or a salt thereof, the compound is selected from the group consisting or a pharmaceutically acceptable salt thereof, wherein G is as defined for formula (I), or any applicable variation thereof, and the alpha carbon of the amino acid may have absolute stereochemistry R or S as indicated. In such an embodiment, the alpha carbon of the amino acid is in the absolute stereochemistry S. When the alpha carbon of the amino acid is in the absolute stereochemical configuration S, in some embodiments, such compound is substantially isolated from the corresponding compound in which the amino acid is in the absolute stereochemical configuration R , such as when a composition comprising the compound in the absolute stereochemical configuration S comprises no more than 5%, or 3%, or 1%, or 0.5%, or 0.1% by weight of the corresponding compound having the stereochemical configuration In another such embodiment, the alpha carbon of the amino acid is in absolute stereochemistry R. When the alpha carbon of the amino acid is in the absolute stereochemical configuration R, in some embodiments, such compound is substantially isolated from the corresponding compound in which the amino acid is in absolute stereochemical configuration S, such as when a composition comprising the compound in the absolute stereochemical configuration R comprises no more than 5%, or 3%, or 1%, or 0.5%, or 0.1% by weight of the corresponding compound having the absolute stereochemical configuration S. In another embodiment, there is provided a composition comprising a preceding compound, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier. In such an embodiment, there is provided a composition comprising a mixture of a compound in which the alpha carbon of the amino acid is in the S stereochemical configuration and a compound in which the alpha carbon of the amino acid is in the R stereochemical configuration.

[0166] Also provided in another embodiment is a compound of formula (I), or a salt thereof, in which G is -C(O)R2 and R2 is C1-C6 alkyl substituted by 0 to 5 R2a groups. In one aspect of the above embodiment, R2 is C1-C6 unsubstituted alkyl (e.g., C4-C6 unsubstituted alkyl). In one aspect of the above embodiment, the C1-C6 alkyl of R2 is straight chain alkyl (e.g., n-butyl). In another aspect of the above embodiment, the C1-C6 alkyl of R2 is branched alkyl (e.g., iso-butyl). In another aspect of the above embodiment, R2 is C1-C5 alkyl substituted by 1 to 5 groups R2a, wherein each R2a is independently selected from halogen, C1-C6 alkyl, C3-C8 cycloalkyl, 3- to 12-membered heterocyclyl, C6- C14 aryl, 5- to 10-membered heteroaryl, -CN, -OR5, -NR6R7, -NR5C(O)OR6, and -S(O)2R5, wherein C1-C6 alkyl, C3-C8 cycloalkyl, 3-membered heterocyclyl 12-membered, C6-C14 aryl and 5- to 10-membered heteroaryl of R2a are optionally independently substituted by R4a. In another aspect of the above embodiment, R2 is C2-C5 alkyl substituted by 1 to 5 R2a groups, wherein at least one of the R2a groups is halogen (for example, R2C5 alkyl substituted by 2 to 3 fluorine groups). In another aspect of the above embodiment, R2 is C1-C5 alkyl (e.g., C1-C3 alkyl) substituted by 1 to 5 R2a groups, wherein at least one of the R2a groups is C3-C8 cycloalkyl (e.g., cyclopropyl, cyclobutyl, and cyclo -hexyl). In another aspect of the above embodiment, R2 is C1-C3 alkyl substituted by C3-C6 cycloalkyl, wherein the C3-C6 cycloalkyl is substituted by 0 to 5 groups selected from the group consisting of halogen, C1-C6 alkyl (e.g. , methyl) and -OR5(e.g., -OH and -OCH3). In another aspect of the above embodiment, R2 is C1-C3 alkyl substituted by C3-C6 cycloalkyl, wherein the C3-C6 cycloalkyl is unsubstituted. In another aspect of the above embodiment, R2 is C1-C5 alkyl substituted by 1 to 5 groups R2a, wherein at least one of the groups R2a is 3 to 12 membered heterocyclyl (for example R2 is C1 alkyl substituted by 6 membered heterocyclyl). In another aspect of the above embodiment, R2 is C1-C5 alkyl substituted by 1 to 5 groups R2a, wherein at least one of the groups R2a is C6-C14 aryl, wherein the C6-C14 aryl is optionally independently substituted by halogen or C1 -C6 alkyl substituted by 0 to 5 halogen (e.g., R2a is unsubstituted phenyl or phenyl substituted by 1 to 5 halogen. In another aspect of the above embodiment, R2 is C2-C5 alkyl (e.g., C5 alkyl) substituted by 1 to 5 R2a groups, wherein at least one of the R2a groups is 5 to 10 membered heteroaryl substituted by 0 to 5 R4a groups (e.g., R2a is unsubstituted pyridinyl). 5 R2a groups, wherein at least one of the R2a groups is -OR5, wherein each R5 is independently selected from hydrogen, C1-C6 alkyl, and C6-C14 aryl (e.g., R5 is C6-C14 aryl substituted by 0 to 5 halogens). In another aspect of the above embodiment, R2 is C1-C5 alkyl substituted by 1 to 5 R2a groups, wherein at least one of the R2a groups is -CN, -NR6R7, -NR5C(O)OR6, or -S(O) 2R5. In another aspect of the above embodiment, R2 is C1-C5 alkyl substituted by 2 to 5 groups R2a, wherein each R2a is independently selected from halogen, C1-C6 alkyl, C3-C8 cycloalkyl, 5- to 10-membered heteroaryl, C6- C14 aryl, -CN, -OR5e -NR5C(O)OR6. In another aspect of the above embodiment, R2 is C1-C5 alkyl substituted by 2 to 5 groups R2a, wherein at least one group R2a is phenyl substituted by 0 to 5 halogens and at least one group R2a is OR5, wherein each R5 is independently selected from hydrogen and C1-C6 alkyl.

[0167] Also provided is a compound of formula (I), or a salt thereof, wherein G is –C(O)R2 and R2 is selected from the group consisting of: thereof, where G is -C(O)R2 and R2 is selected from the group as defined for formula (I).

[0168] Also provided in another embodiment is a compound of formula (I), or a salt thereof, in which G is -C(O)R2 and R2 is C3-C8 cycloalkyl substituted by 0 to 5 R2b groups. In another aspect of the previous embodiment, the C3-C8 cycloalkyl of R2 is monocyclic. In another aspect, the C3-C8 cycloalkyl of R2 is bicyclic (e.g., fused, spiro or bridged). In another aspect, R2 is unsubstituted C3-C8 cycloalkyl (e.g., bicyclo[2.2.2]octanyl). In another aspect of the above embodiment, R2 is C3-C8 cycloalkyl substituted by 1 to 5 groups R2b, wherein each R2 is independently selected from halogen, C1-C6 alkyl, 3- to 12-membered heterocyclyl, C6-C14 aryl, heteroaryl of 5 to 10 members and -OR5. In another aspect of the above embodiment, R2 is C3-C6 cycloalkyl (e.g., cyclopropyl or cyclohexyl) substituted by 1 to 5 R2b groups, wherein at least one of the R2b groups is halogen (e.g., fluorine). In another aspect of the above embodiment, R2 is C3-C6 cycloalkyl substituted by 1 to 5 groups R2b, wherein at least one of the groups R2 is C1-C6 alkyl, wherein the C1-C6 alkyl of R2b is substituted by 0 to 5 groups R4a( for example, R2b is C1-C2 alkyl substituted by 1 to 5 R4a, wherein each group R4a is independently selected from phenyl substituted by 0 to 5 halogens and 6-membered heteroaryl substituted by 0 to 5 halogens). In another aspect of the above embodiment, R2 is C3-C6 cycloalkyl substituted by 1 to 5 R2b groups, wherein at least one of the R2b groups is a 3- to 12-membered heterocyclyl (e.g., tetrahydro-2H-pyranyl or benzodioxolyl). In another aspect of the above embodiment, R2 is C3-C4 cycloalkyl substituted by 1 to 5 R2b, wherein at least one of the groups R2 is C6-C14 aryl substituted by 0 to 5 R4a, wherein each R4a is independently selected from halogen, C1 -C6 alkyl, and -OR8 (for example, R2bé unsubstituted phenyl or R2bé phenyl substituted by fluorine, methyl, tert-butyl or -OCF3). In another aspect of the above embodiment, R2 is C3-C7 cycloalkyl substituted by 1 to 5 R2b groups, wherein at least one of the R2b groups is a 5- to 10-membered heteroaryl group (e.g., pyridinyl or isoquinolinyl). In another aspect of the above embodiment, R2 is C3-C6 cycloalkyl substituted by groups 2 to 5 R2b, wherein each R2 is independently selected from halogen (e.g., fluorine), C6-C14 aryl (e.g., phenyl), and -OR5 (e.g. -OH). In another aspect of the above embodiment, R2 is C3-C6 cycloalkyl substituted by 2 to 5 R2b groups, wherein at least one group R2 is halogen (e.g., fluorine) and at least one group R2 is phenyl substituted by 0 to 5 C1-C6 alkyl (e.g. - CH3).

[0169] There is also provided a compound of formula (I), or a salt thereof, in which G is -C(O)R2 and R2 is selected from the group e, where R2 is as defined for formula (I), and n is 0, 1, 2, or 3. In one variation, n is 0. In another variation, n is 1. In another variation, n is 2. In yet another variation , n is 3.

[0170] Also provided in another embodiment is a compound of formula (I), or a salt thereof, in which G is -C(O)R2 and R2 is a 3- to 12-membered heterocyclyl substituted by 0 to 5 R2c groups. In another aspect of the above embodiment, the 3- to 12-membered heterocyclyl of R2 is monocyclic. In another aspect of the above embodiment, the 3- to 12-membered heterocyclyl of R2 is bicyclic (e.g., fused, spiro or bridged). In another aspect of the above embodiment, unsubstituted 4- to 10-membered R2heterocyclyl (e.g., azetidinyl, pyrrolidinyl, piperidinyl, oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, oxabicyclohexanyl, oxabicyclooctanyl, tetrahydro-2H-thiopyranyl , morpholinyl, benzodioxanyl, 3-oxabicyclo[3.1.0]hexanyl, or 8-oxabicyclo[3.2.1]octanyl). In another aspect of the above embodiment, R2 is 3 to 12 membered heterocyclyl substituted by 1 to 5 groups R2c, wherein each R2 is independently selected from oxo, halogen, C1-C6 alkyl, C6-C14 aryl, 5 to 10 members, -CN, -OR5, -C(O)R5, -C(O)OR5, and -S(O)2R5. In another aspect of the above embodiment, R2 is 4 to 6 membered heterocyclyl (e.g., oxetanyl, tetrahydropyranyl or azetidinyl) substituted by 1 to 5 R2c groups, wherein at least one of the R2c groups is C1-C6 alkyl, wherein the C1-C6 alkyl of R2c is substituted by 0 to 5 R4a groups. In another aspect of the above embodiment, R2c is C1-C2 alkyl substituted by 1 to 5 R4a groups, wherein each R4a group is independently selected from halogen; phenyl substituted by 0 to 5 halogens; 6-membered heteroaryl (e.g., pyridinyl or pyrimidinyl) substituted by 0 to 5 halogens; and -NR8C(O)OR10 (for example -NHC(O)O-1-butyl). In another aspect of the above embodiment, R2 is 4 to 6 membered heterocyclyl substituted by 1 to 5 R2c groups, wherein at least one of the R2c groups is C6-C14 unsubstituted aryl (e.g., phenyl). In another aspect of the above embodiment, R2 is 4- to 6-membered heterocyclyl (e.g., 5-membered heterocyclyl) substituted by 1 to 5 groups R2c, wherein at least one of the groups R2 is 5- to 10-membered heteroaryl substituted by 0 to 5 C1-C6 alkyl (e.g. R2c is pyrazolyl substituted by -CH3). In another aspect of the above embodiment, R2 is 4 to 6 membered heterocyclyl substituted by 1 to 5 R2c groups, wherein at least one R2c group is -C(O)R5, -C(O)OR5or -S(O)2R5, wherein each R5 is independently C1-C6 alkyl. In another aspect of the above embodiment, R2 is 4 to 6 membered heterocyclyl (e.g., 1,2-dihydropyridinyl) substituted by 1 to 5 R2c groups, wherein at least one R2 group is oxo. In another aspect of the above embodiment, R2 is a 4 to 6 membered heterocyclyl substituted by 2 to 5 R2c groups, wherein each R2 is independently selected from halogen, C1-C6 alkyl, -C(O)R5e -C(O)OR5 . In another aspect of the above embodiment, R2 is a 4- to 6-membered heterocyclyl substituted by 2 to 5 R2c groups, wherein at least one group R2 is C1-C6 alkyl substituted by 0 to 5 halogen and at least one group R2 is C(O) R5or -C(O)OR5. In another aspect of the above embodiment, R2 is azetidinyl, pyrrolidinyl, piperidinyl, oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, oxabicyclohexanyl, oxabicyclooctanyl, tetrahydro-2H-thiopyranyl, morpholinyl, or benzodioxanyl, each of which is replaced by 0 to 5 R2cgroups.

[0171] Also provided is a compound of formula (I), or a salt thereof, in which G is -C(O)R2 and R2 is selected from the group , where R2c is as defined for formula (I), and n is 0, 1, 2, or 3. In one variation, n is 0. In another variation, n is 1. In another variation, n is 2. In yet another variation, n is 3. In the above structures that depict a chemical moiety -N(H)- and n is 1, 2, or 3, it is understood that one of the R2cgroups can replace the hydrogen atom in the chemical moiety -N(H )-(e.g. n is 1 and R2

[0172] Also provided in another embodiment is a compound of formula (I), or a salt thereof, in which G is -C(O)R2and R2is C6-C14 aryl substituted by groups 0 to 5 R2d. In another aspect of the above embodiment, R2 is C6-C10 unsubstituted aryl (e.g., phenyl, indanyl or 1,2,3,4-tetrahydronaphthalenyl). In another aspect of the above embodiment, R2 is C6-C10 aryl substituted by 1 to 5 groups R2d, wherein each R2 is independently selected from halogen, C1-C6 alkyl, C3-C8 cycloalkyl, 3- to 12-membered heterocyclyl, heteroaryl of 5- to 10-membered, -CN, and -OR5, wherein the C1-C6 alkyl, C3-C8 cycloalkyl, 3- to 12-membered heterocyclyl, and 5- to 10-membered heteroaryl of R2d are each independently substituted by 0 to 5 halogens, C1-C6 alkyl or OR8. In another aspect of the above embodiment, R2 is C6-C10 aryl substituted by 1 to 5 R2d groups, wherein at least one of the R2 groups is halogen (e.g., fluorine or chlorine). In another aspect of the above embodiment, R2 is C6-C10 aryl substituted by 1 to 5 groups R2d, wherein at least one of the groups R2 is C1-C6 alkyl, wherein the C1-C6 alkyl of R2d is substituted by groups 0 to 5 R4a( e.g. R2d -CH3). In another aspect of the above embodiment, R2 is C1-C2 alkyl substituted by 1 to 5 R4a groups, wherein each R4a group is independently selected from halogen and OR8 (for example, R2 is -CH2 (OH), or -CF3). In another aspect of the above embodiment, R2 is C6-C10 aryl (e.g., phenyl) substituted by 1 to 5 R2d groups, wherein at least one of the R2 groups is C3-C6 cycloalkyl (e.g., cyclopropyl). In another aspect of the above embodiment, R2 is C6-C10 aryl (e.g., phenyl) substituted by 1 to 5 R2d groups, wherein at least one of the R2d groups is 6-membered heterocyclyl (e.g., morpholinyl). In another aspect of the above embodiment, R2 is C6-C10 aryl (e.g., phenyl) substituted by 1 to 5 R2d groups, wherein at least one of the R2d groups is 5- to 6-membered heteroaryl (e.g., pyrazolyl, thiazolyl, or pyridinyl ), wherein the heteroaryl of R2 is replaced by 0 to 5 C1-C6 alkyl groups (e.g. -CH3). In another aspect of the above embodiment, R2 is C6-C10 aryl (e.g., phenyl) substituted by 1 to 5 R2d groups, wherein at least one of the R2d groups is -OR5, wherein each R5 is independently selected from C1-C2 alkyl substituted by 0 to 5 groups selected from halogen (e.g., fluorine) and -OR10 (e.g., -OCH3). In another aspect of the above embodiment, R2 is C6-C10 aryl (e.g., phenyl) substituted by 2 to 5 R2d groups, wherein each R2 is independently selected from halogen, C1-C6 alkyl, -CN, and -OR5. In another aspect of the above embodiment, R2 is C6-C10 aryl (e.g., phenyl) substituted by 2 to 5 R2d groups, wherein at least two of the R2d groups are halogen (e.g., fluorine or chlorine). In another aspect of the above embodiment, R2 is C6-C10 aryl (e.g., phenyl) substituted by groups 2 to 5 R2d, wherein at least one of the groups R2 is C1-C6 alkyl and at least one of the groups R2 is selected from the group which consists of halogen, -CN and -OR5. In another aspect of the above embodiment, R2 is phenyl, indanyl or 1,2,3,4-tetrahydronaphthalenyl, each of which is substituted by 0 to 5 R2d groups.

[0173] Also provided is a compound of formula (I), or a salt thereof, wherein G is -C(O)R2 and R2 is selected from the group consisting of: , where R2 is as defined for formula (I), and n is 0, 1, 2, or 3. In one variation, n is 0. In another variation, n is 1. In another variation, n is 2. In yet another variation, n is 3.

[0174] Also provided in another embodiment is a compound of formula (I), or a salt thereof, in which G is -C(O)R2 and R2 is a 5- to 10-membered heteroaryl substituted by 0 to 5 R2e groups. In another aspect of the above embodiment, R2 is unsubstituted 5- to 10-membered heteroaryl (e.g., pyridinyl, pyrrolopyridinyl, quinolinyl or 4,5,6,7-tetrahydro-indazolyl). In another aspect of the above embodiment, R2 is a 5- to 10-membered heteroaryl substituted by 1 to 5 R2e groups, wherein each R2e is independently selected from halogen, C1-C6 alkyl and -OR5. In another aspect of the above embodiment, R2 is 5 to 10 membered heteroaryl (e.g., pyridinyl) substituted by 1 to 5 R2e groups, wherein at least one of the R2e groups is halogen. In another aspect of the above embodiment, R2 is a 5- to 10-membered heteroaryl (e.g., pyridinyl, pyrimidinyl, pyrrolopyridinyl or indazolyl) substituted by 1 to 5 groups R2e, wherein at least one of the groups R2e is C1-C4 alkyl, wherein the C1-C4 alkyl of R2e is substituted by 0 to 5 halogen groups (e.g., R2e is -CH3 or -CF3). In another aspect of the above embodiment, R2 is 5 to 10 membered heteroaryl substituted by 2 to 5 R2e, wherein each R2e is independently selected from halogen, C1-C6 alkyl and -CN. In another aspect of the above embodiment, R2 is a 5- to 10-membered heteroaryl substituted by 2 to 5 R2e groups, wherein at least two of the R2 groups are halogen. In another aspect of the above embodiment, R2 is a 5- to 10-membered heteroaryl substituted by 2 to 5 R2e groups, wherein at least two of the R2 groups are C1-C6 alkyl. In another aspect of the above embodiment, R2 is a 5- to 10-membered heteroaryl (e.g., pyridinyl or pyrimidinyl) substituted by 3 to 5 R2e groups, wherein each R2e is independently selected from halogen, C1-C6 alkyl and -CN. In another aspect of the above embodiment, R2 is a 5- to 10-membered heteroaryl (e.g., pyridinyl or pyrimidinyl) substituted by three -CH3 groups. In another aspect of the above embodiment, R2 is a 5- to 10-membered heteroaryl (e.g., pyridinyl or pyrimidinyl) substituted by two -CH3 groups and a halogen group. In another aspect of the above embodiment, R2 is pyrazolyl, pyridyl, pyrimidinyl, indazolyl, pyrrolopyridinyl, quinolinyl or 4,5,6,7-tetrahydro-indazolyl, each of which is substituted by 0 to 5 R2e groups.

[0175] Also provided is a compound of formula (I), or a salt thereof, wherein G is -C(O)R2 and R2 is selected from the group consisting of: , where R2e is as defined for formula (I), and n is 0, 1, 2, or 3. In one variation, n is 0. In another variation, n is 1. In another variation, n is 2. In yet another variation, n is 3.

[0176] Also provided in another embodiment is a compound of formula (I), or a salt thereof, in which G is -C(O)R2and R2is -OR2f. In another aspect of the above embodiment, R2 is selected from the group consisting of C1-C6 alkyl, C3-C8 cycloalkyl, 3- to 12-membered heterocyclyl, C6-C14 aryl and 5- to 10-membered heteroaryl.

[0177] Also provided in another embodiment is a compound of formula (I), or a salt thereof, in which G is -C(O)R2, R2 is -OR2f, and R2f is C1-C6 alkyl substituted by 0 to 5 R2i groups. In another aspect of the previous embodiment, R2 is C1-C6 unsubstituted alkyl. In another aspect of the above embodiment, R2 is C1-C6 alkyl substituted by 1 to 5 R2i groups, wherein each R2i is independently selected from the group consisting of halogen, C1-C6 alkyl, C3-C8 cycloalkyl, heterocyclyl from 3 to 12 members, C6-C14 aryl, 5- to 10-membered heteroaryl, -OR5, -NR5C(O)R6, and -NR5C(O)OR6, wherein C1-C6 alkyl, C3-C8 cycloalkyl, 3- to 12-membered heterocyclyl members, C6-C14 aryl, and 5- to 10-membered heteroaryl of R2i is substituted by 0 to 5 groups selected from the group consisting of halogen, -CN, -OR8, and C1-C6 alkyl optionally substituted by halogen. In another aspect of the above embodiment, R2 is C1-C6 alkyl substituted by 1 to 5 R2i groups, wherein at least one of the R2i groups is halogen. In another aspect of the above embodiment, R2 is C1-C6 alkyl substituted by 1 to 5 R2i groups, wherein at least one of the R2i groups is phenyl. In another aspect of the above embodiment, R2 is C1-C6 alkyl substituted by 1 to 5 R2i groups, wherein at least one of the groups R2i is -NR5C(O)OR6, wherein R5 is hydrogen and R6 is C1-C6 alkyl (e.g., R2i is -NHC(O)O- t-butyl). In another aspect of the above embodiment, R2 is C1-C6 alkyl substituted by 1 to 5 R2i groups, wherein at least one of the R2i groups is -NR5C(O)R6, wherein R5 is hydrogen and R6 is C1-C6 alkyl (e.g. R2i is -NHC(O)CH3).

[0178] Also provided is a compound of formula (I), or a salt thereof, wherein G is -C(O)R2 and R2 is selected from the group consisting of: , where R2i is as defined for formula (I).

[0179] Also provided in another embodiment is a compound of formula (I), or a salt thereof, in which G is -C(O)R2, R2 is -OR2f, and R2f is C3-C8 cycloalkyl substituted by 0 to 5 R2i groups. In another aspect of the above embodiment, R2 is unsubstituted C3-C8 cycloalkyl (e.g., cyclopentyl, cyclohexyl or spiro[2.3]hexanyl). In another aspect of the above embodiment, R2 is C3-C8 cycloalkyl substituted by 1 to 5 R2i groups, wherein each R2i is independently selected from the group consisting of halogen, C1-C6 alkyl, C2-C6 alkynyl, C6-C14 aryl, and 5- to 10-membered heteroaryl, wherein the C1-C6 alkyl, C2-C6 alkynyl, C6-C14 aryl, and 5- to 10-membered heteroaryl of R2 are substituted by 0 to 5 groups selected from the group consisting of C1- C6 alkyl and C6-C14 aryl. In another aspect of the above embodiment, R2 is C3-C6 cycloalkyl (e.g., cyclopropyl or cyclobutyl) substituted by 1 to 5 R2i groups, wherein at least one R2i group is C1 alkyl. In another aspect of the above embodiment, R2 is C3-C6 cycloalkyl substituted by 1 to 5 R2i groups, wherein at least one R2i group is C2 alkynyl substituted by 0 to 1 phenyl group. In another aspect of the above embodiment, R2 is C3-C6 cycloalkyl substituted by 1 to 5 R2i groups, wherein at least one R2i group is phenyl substituted by 0 to 3 C1-C6 alkyl groups or is pyrazolyl substituted by 0 to 3 C1-C6 groups alkyl, whose C1-C6 alkyl groups in phenyl or pyrazolyl of R2i can be the same or different.

[0180] Also provided is a compound of formula (I), or a salt thereof, wherein G is -C(O)R2 and R2 is selected from the group consisting of: , where R2i is as defined for formula (I) and n is 0, 1, or 2. In one variation, n is 0. In another variation, n is 1. In yet another variation, n is 2.

[0181] Also provided in another embodiment is a compound of formula (I), or a salt thereof, in which G is -C(O)R2, R2 is -OR2f, and R2f is a 3- to 12-membered heterocyclyl substituted by groups 0 to 5 R2i. In another aspect of the above embodiment, R2 is an unsubstituted 3- to 12-membered heteroaryl (e.g., azetidinyl or pyrrolidinyl). In another aspect of the above embodiment, R2 is a 3- to 12-membered heterocyclyl substituted by 1 to 5 R2i groups, wherein each R2i is independently selected from the group consisting of C1-C6 alkyl, C2-C6 alkynyl, C6-C14 aryl, -C(O)R5, -C(O)OR5e -S(O)2R5. In another aspect of the above embodiment, R2 is a 3- to 12-membered heterocyclyl substituted by 1 to 5 R2i groups, wherein at least one R2i group is C1 C6 alkyl or C2-C6 alkynyl, each of which is unsubstituted or substituted by a group phenyl. In another aspect of the above embodiment, R2 is a 3 to 12 membered heterocyclyl substituted by 1 to 5 R2i, wherein at least one group R2 is C6-C14 aryl (e.g., phenyl) substituted by 0 to 5 R4a, wherein each R4a is independently selected from the group consisting of halogen and C1-C6 alkyl (e.g. isopropyl). In another aspect of the above embodiment, R2f is 3 to 12 membered heterocyclyl (e.g., azetidinyl or pyrrolidinyl) substituted by 1 to 5 R2i groups, wherein at least one R2i group is -C(O)R5, wherein R5 is C1-C6 alkyl (e.g. R2i is - C(O)CH3). In another aspect of the above embodiment, R2 is a 3- to 12-membered heterocyclyl substituted by 1 to 5 R2i groups, wherein at least one group R2i is -C(O)OR5, wherein R5 is C1-C6 alkyl (e.g., R2i is - C(O)O-t-butyl). In another aspect of the above embodiment, R2 is a 3- to 12-membered heterocyclyl (e.g., azetidinyl or pyrrolidinyl) substituted by 1 to 5 R2i groups, wherein at least one R2i group is -S(O)2R5, wherein R5 is C1- C6 alkyl (e.g. R2i is -S(O)2CH3). In another aspect of the above embodiment, R2 is a 3- to 12-membered heterocyclyl substituted by 2 to 5 R2i groups, wherein at least one R2i group is -C(O)R5, -C(O)OR5, or -S(O)2R5 , where R5 is C1-C6 alkyl (for example, R5 is - CH3 or t-butyl). In another aspect of the above embodiment, R2 is azetidinyl, pyrrolidinyl or tetrahydropyranyl, each of which is optionally substituted by 0 to 5 R2i.

[0182] Also provided is a compound of formula (I), or a salt thereof, wherein G is -C(O)R2 and R2 is selected from the group consisting of: , where R2i is as defined for formula (I) and n is 0, 1, or 2. In one variation, n is 0. In another variation, n is 1. In yet another variation, n is 2. In the above structures that depict a chemical portion -N(H)- and n is 1 or 2, it is understood that one of the groups R2i can replace the hydrogen atom in the chemical portion R2Í pH C)'J chemical -N(H)- (for example, n is 1 and

[0183] Also provided in another embodiment is a compound of formula (I), or a salt thereof, in which R2f, and R2f is C6-C14 aryl substituted by 0 to 5 R2i groups. In another aspect of the above embodiment, R2 is C6-C14 unsubstituted aryl (e.g., indanyl or 1,2,3,4-tetrahydronaphthalenyl).

[0184] Also provided is a compound of formula (I), or a salt thereof, wherein G is -C(O)R2 and R2 is selected from the group consisting of: -L and J_, wherein R2i is as defined for formula (I) and n is 0, 1 or 2. In one variation, n is 0. In another variation, n is 1. In yet another variation, n is 2.

[0185] Also provided in another embodiment is a compound of formula (I), or a salt thereof, in which G is -C(O)R2, R2 is -OR2f, and R2f is 5- to 10-membered heteroaryl substituted by 0 to 5 R2i groups. In another aspect of the above embodiment, R2 is unsubstituted 5- to 10-membered heteroaryl.

[0186] Also provided in another embodiment is a compound of formula (I), or a salt thereof, in which G is -C(O)R2and R2is -NR2gR2h. In another aspect of the previous embodiment, R2 is hydrogen and R2 is C1-C6 alkyl substituted by 0 to 5 halogens. In another aspect of the above embodiment, R2 is C1-C6 alkyl substituted by 0 to 5 halogens and R2 is C1-C6 alkyl substituted by 0 to 5 halogens.

[0187] Also provided is a compound of formula (I), or a salt thereof, in which G is -C(O)R2 and R2 is selected from the group consisting of

[0188] There is also provided a compound of formula (I), or a salt thereof, in which G is -C(O)R2 and R2 is selected from the group

[0189] Also provided is a compound of formula (I), or a salt thereof, wherein G is –C(O)R2 and R2 is selected from the group consisting of:

[0190] There is also provided a compound of formula (I), or a salt thereof, in which G is –C(O)R2 and R2 is selected from the group consisting of:

[0191] Also provided in another embodiment is a compound of formula (I), or a salt thereof, where G is R3. In one aspect, R3 is a 5- to 10-membered heteroaryl (e.g., pyrimidinyl or quinazolinyl) substituted by 0 to 5 R3e groups, wherein each R3e group is independently selected from halogen; C1-C6 alkyl optionally substituted by halogen; 5- to 10-membered heteroaryl optionally substituted by halogen or C1-C6 alkyl; and C1-C6 alkoxy. In one aspect, R3 is unsubstituted 5-10 membered heteroaryl. In one aspect, R3 is a 5- to 10-membered heteroaryl substituted by 1 to 5 R3e groups, wherein each R3e group is independently selected from halogen, C1-C6 alkyl and C6-C14 aryl. In one aspect, R3 is a 5- to 10-membered heteroaryl substituted by 1 to 5 R3e groups, wherein at least one R3e group is halogen. In one aspect, R3 is 5 to 10 membered heteroaryl substituted by 1 to 5 R3e groups, wherein at least one R3e group is C1-C4 alkyl. In one aspect, R3 is 5 to 10 membered heteroaryl substituted by 1 to 5 R3e groups, wherein at least one R3e group is phenyl. In one aspect, R3 is 5 to 10 membered heteroaryl substituted by 2 to 5 R3e groups, wherein at least one R3e group is C1-C6 alkyl, and wherein at least one R3e group is C6-C14 aryl.

[0192] There is also provided a compound of formula (I), or a salt thereof, in which G is R3 and R3 is selected from the group that that each R3e is independently R4. In the above structures where the chemical moiety -N(H)- is present as shown and the structure is replaced by at least one R3e group, it is understood that one of the R3e groups can replace the hydrogen atom in the chemical moiety -

[0193] There is also provided a compound of formula (I), or a salt thereof, in which G is R3 and R3 is selected from the group that

[0194] There is also provided a compound of formula (I), or a salt thereof, in which G is R3 and R3 is selected from the group that

[0195] There is also provided a compound of formula (I), or a salt thereof, in which G is R3 and R3 is selected from the group that

[0196] Also provided is a compound of formula (I), or a salt thereof, in which G is selected from the group consisting of:

[0197] In one aspect, a compound of formula (I) or a salt thereof is provided, wherein the compound has one or more of the following characteristics:

[0198] (I) R1é

[0199] (II)-L1-O-L2-Y-L3- are taken together to form a chemical moiety selected from the group consisting of: ;

[0200] (III) G is -C(O)R2or R3where:

[0201] (A) R2 is:

[0202] (i) C1-C6 alkyl optionally substituted by R2a, such as methyl, ethyl, isopropyl or tert-butyl, each of which is substituted by 0 to 5 R2a groups;

[0203] (ii) C3-C8 cycloalkyl optionally substituted by R2b, such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, or spiro[3.3]heptanyl, each of which is substituted by 0 to 5 R2b groups;

[0204] (iii) 3- to 12-membered heteroaryl optionally substituted by R2c, such as 4 to 6-membered heteroaryl containing 1 or 2 heteroatoms selected from O and N (e.g., azetidinyl, pyrrolidinyl, piperidinyl, oxetanyl, tetra -hydrofuranyl or tetrahydropyranyl), each of which is substituted by 0 to 5 R2c groups;

[0205] (iv) C6-C14 aryl optionally substituted by R2d, such as phenyl substituted by 0 to 5 R2d groups; or

[0206] (v) 5 to 10 membered heteroaryl substituted by R2e, such as pyridinyl, pyrimidinyl, indazolyl, or quinolinyl, each of which is substituted by 0 to 5 R2e groups; It is

[0207] wherein each R2a, R2b, R2d, and R2e is independently R4, R2ce oxo or R4, and R4 is halogen, C1-C6 alkyl, C3-C8 cycloalkyl, 3- to 12-membered heteroaryl, C6-C14 aryl, 3- to 12-membered heteroaryl, 5 to 10 members, -CN, -OR5, -C(O)R5, -C(O)OR5, -C(O)NR6R7, -NR5C(O)OR6, or -S(O)2R5, where the C1-C6 alkyl, C3-C8 cycloalkyl, 3- to 12-membered heteroaryl, C6-C14 aryl and 5- to 10-membered heteroaryl of R4 are optionally independently substituted R4a, where R4a is halogen, -OR8, -NR8R9, -C (O)OR8, -NR8C(O)OR10, -CN, 5- to 10-membered heteroaryl, C6-C14 aryl or C1-C6 alkyl, where

[0208] R8 is hydrogen or C1-C6 alkyl optionally substituted by halogen,

[0209] R9 is hydrogen, and

[0210] R10 is C1-C6 alkyl optionally substituted by halogen; It is

[0211] (B) R3 is:

[0212] (vi) C1-C6 alkyl optionally substituted by R3a, such as methyl or ethyl, each of which is substituted by 1 group R3a, wherein R3a is phenyl or quinazolinyl; or

[0213] (vii) 5 to 10 membered heteroaryl substituted by R3e, such as pyrimidinyl, quinazolinyl, or pyrazolopyrimidinyl, each of which is substituted by 0 to 5 R3e groups;

[0214] In one aspect of this variation, (I) and (II) apply, and G is - C(O)R2. In another aspect of this variation, (I) and (II) apply, and G is R3. In another variation, (I) and (II) apply, G is -C(O)R2, and (i) applies. In another variation, (I) and (II) apply, G is -C(O)R2, and (ii) applies. In another variation, (I) and (II) apply, G is -C(O)R2, and (iii) applies. In another variation, (I) and (II) apply, G is -C(O)R2, and (iv) applies. In another variation, (I) and (II) apply, G is -C(O)R2, and (v) applies. In another variation, (I) and (II) apply, G is R3, and (vi) applies. In another variation, (I) and (II) apply, G is R3, and (vii) applies.

[0215] Also provided is a compound of formula (I), or a salt thereof, wherein G is -C(O)R2, R2 is C1-C6 alkyl optionally substituted by R2a, C3-C8 cycloalkyl optionally substituted by R2b , 3- to 12-membered heteroaryl optionally substituted by R2c, C6-C14 aryl optionally substituted by R2d, or 5- to 10-membered heteroaryl substituted by R2e, wherein each R2a, R2b, R2c, R2d, and R2e is independently R4, wherein each R4 is independently selected from the group consisting of: , wherein each R4a is independently halogen, -OR8, -NR8R9, -C(O)OR8, -NR8C(O)OR10, -CN, 5- to 10-membered heteroaryl, C6-C14 aryl, or C1-C6 alkyl, where R8, R9, and R10 are as defined for formula (I), and n is 0, 1, or 2. In one variation, n is 0. In another variation, n is 1. In yet another variation, n is 2.

[0216] Also provided is a compound of formula (I), or a salt thereof, wherein G is -C(O)R2, R2 is C1-C6 alkyl optionally substituted by R2a, C3-C8 cycloalkyl optionally substituted by R2b , 3- to 12-membered heteroaryl optionally substituted by R2c, C6-C14 aryl optionally substituted by R2d, or 5- to 10-membered heteroaryl substituted by R2e, wherein each R2a, R2b, R2c, R2d, and R2e is independently R4, wherein each R4 is independently selected from the group consisting of: ,

[0217] When a chemical portion is contemplated, it is understood that the chemical portion can be attached to the rest of the structure in any available position. For example, 3-chloro-5-methylapyridinyl can be attached to the rest of the structure at the 2-, 4-, or 6- position (i.e., 3-chloro-5-methylapyridin-2-yl, 3-chloro-5-methylapyridinyl -4-yl or 3-chloro-5-methylapyridin-6-yl, respectively). The R2 and R3 groups described herein are shown to be attached to specific positions (e.g., pyrimid-4-yl, quinazolin-4-yl, isoquinolin-1-yl), but they can also be attached through any other available valence ( e.g., pyrimid-2-yl, quinazolin-2-yl, isoquinolin-3-yl, respectively).

[0218] Representative compounds are listed in Table 1. TABLE 1

[0219] The structures in Table 1 are drawn without stereochemistry. Atoms that can be stereocenters are indicated by an asterisk (*). The structures are intended to encompass all possible stereoisomers of the compound depicted, as well as mixtures of stereoisomers in any proportion. Thus, racemic mixtures, scalemic mixtures, mixtures of enantiomers in any proportion, mixtures of diastereomers in any proportion, and mixtures of enantiomers and diastereomers in any proportion are covered, as well as individual stereochemically pure compounds.

[0220] In some embodiments, there is provided a compound selected from the compounds depicted in Table 1, or a stereoisomer thereof (including a mixture of two or more stereoisomers thereof), or a salt thereof. In some embodiments, the compound is a salt of a compound selected from the compounds in Table 1, or a stereoisomer thereof.

[0221] Representative compounds are listed in Table 2 (Figure 1). In some embodiments, there is provided a compound selected from the compounds depicted in Table 2, or a stereoisomer thereof (including a mixture of two or more stereoisomers thereof), or a salt thereof. In some embodiments, the compound is a salt of a compound selected from the compounds in Table 2, or a stereoisomer thereof. "Flat" versions of all compounds represented in Table 2 are also contemplated in this disclosure, including flat versions of any specific stereoisomeric forms in the Table.

[0222] In relation to the structures in Figure 1, Table 2, reference to compound numbers in the table in some cases depicts a particular stereoisomeric form of the compound number, as will be evident from the chemical structure depicted. For example, Table 2 lists

[0223] as Compound 185. It is appreciated that the depicted compound is a specific stereochemical form of Compound 185, in particular the form produced by Example 365.

[0224] In one variation, the compound detailed herein is selected from the group consisting of:

[0225] N-(1-methyl-1H-indazol-4-carbonyl)-O-(4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl)homoserine ;

[0226] N-(2-chloro-3-fluorobenzoyl)-O-(4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl)homoserine;

[0227] N-(2-ethylbutanoyl)-O-(4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl)homoserine;

[0228] N-benzoyl-O-(4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl)homoserine;

[0229] N-(4,4-difluorocyclohexane-1-carbonyl)-O-(4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl)homoserine ;

[0230] N-pentanoyl-O-(4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl)homoserine;

[0231] N-(3-fluoro-5-(trifluoromethyl)benzoyl)-O-(4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl)homoserine;

[0232] 2-(2-Ethylbutanamido)-5-(3-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)propoxy)pentanoic acid;

[0233] 2-(2-Chloro-3-fluorobenzamido)-5-(3-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)propoxy)pentanoic acid;

[0234] 2-(1-Methyl-1H-indazol-4-carboxamido)-5-(3-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)propoxy acid) pentanoic;

[0235] 2-(3-(1-methyl-1H-pyrazol-4-yl)benzamido)-5-(3-(5,6,7,8-tetrahydro-1,8-naphthyridin-2- yl)propoxy)pentanoic acid;

[0236] 2-(2-Chloro-3-fluorobenzamido)-6-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethoxy)hexanoic acid;

[0237] 2-(3-(1-methyl-1H-pyrazol-4-yl)benzamido)-6-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2) acid -yl)ethoxy)hexanoic;

[0238] N-(2-chloro-3-fluorobenzoyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl) homoserine;

[0239] N-(3-fluoro-5-(trifluoromethyl)benzoyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl )cyclobutyl)homoserine;

[0240] 2-(2-Ethylbutanamido)-6-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethoxy)hexanoic acid;

[0241] 2-(1-Methyl-1H-indazol-4-carboxamido)-6-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethoxy acid) hexanoic;

[0242] N-pentanoyl-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine;

[0243] N-(tert-butoxycarbonyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine;

[0244] 2-((tert-butoxycarbonyl)amino)-5-(3-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)propoxy)pentanoic acid;

[0245] N-benzoyl-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine;

[0246] N-(tert-butoxycarbonyl)-O-(4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl)homoserine;

[0247] 2-((tert-butoxycarbonyl)amino)-6-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethoxy)hexanoic acid;

[0248] N-(4-fluorobenzoyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine;

[0249] N-(4-chlorobenzoyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine;

[0250] N-(3-fluorobenzoyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine;

[0251] N-(3-chlorobenzoyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine;

[0252] N-(2-chlorobenzoyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine;

[0253] N-(2-fluorobenzoyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine;

[0254] N-(2,3-difluorobenzoyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine;

[0255] N-(2,4-difluorobenzoyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine;

[0256] N-(2-chloro-4-fluorobenzoyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl) homoserine;

[0257] N-(3-chloro-5-fluorobenzoyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl) homoserine;

[0258] N-(3-chloro-2-fluorobenzoyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl) homoserine;

[0259] N-(3,5-difluorobenzoyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine;

[0260] N-(3,4-difluorobenzoyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine;

[0261] N-(2,3-dichlorobenzoyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine;

[0262] N-(2-chloro-6-fluorobenzoyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl) homoserine;

[0263] N-(2,6-difluorobenzoyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine;

[0264] N-(2,5-difluorobenzoyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine;

[0265] N-(3,4-dichlorobenzoyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine;

[0266] N-picolinoyl-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine;

[0267] N-nicotinoyl-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine;

[0268] N-isonicotinoyl-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine;

[0269] N-(1-methyl-1H-indazol-4-carbonyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl) ethyl)cyclobutyl)homoserine;

[0270] N-(2-methyl-2H-indazol-6-carbonyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl) ethyl)cyclobutyl)homoserine;

[0271] N-(2-methyl-2H-indazol-5-carbonyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl) ethyl)cyclobutyl)homoserine;

[0272] N-(1-methyl-1H-pyrrolo[2,3-b]pyridine-4-carbonyl)-O-(3-(2-(5,6,7,8-tetrahydro-1, 8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine;

[0273] N-(3-hydroxy-2-phenylquinolinayl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl) homoserine;

[0274] N-(2-ethylbutanoyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine;

[0275] N-(3-ethylpentanoyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine;

[0276] N-(1-methyl-1H-pyrrolo[2,3-b]pyridine-5-carbonyl)-O-(3-(2-(5,6,7,8-tetrahydro-1, 8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine;

[0277] O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)- N-(3-(thiazol-5-yl )benzoyl)homoserine;

[0278] N-(3-(hydroxymethyl)benzoyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine ;

[0279] N-(quinoline-5-carbonyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine;

[0280] N-(2-cyclopropylbenzoyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine;

[0281] N-(quinoline-7-carbonyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine;

[0282] N-(quinoline-6-carbonyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine;

[0283] N-(quinoline-8-carbonyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine;

[0284] N-(3-cyclopropylbenzoyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine;

[0285] N-(4-cyclopropylbenzoyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine;

[0286] N-(3-(1-methyl-1H-pyrazol-4-yl)benzoyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin -2-yl)ethyl)cyclobutyl)homoserine;

[0287] N-(2-hydroxy-2-phenylacetyl)-O-(4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl)homoserine;

[0288] N-(2-hydroxy-2-phenylacetyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl) homoserine;

[0289] N-(3-(1-methyl-1H-pyrazol-4-yl)benzoyl)-O-(4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2- ill)butyl)homoserine;

[0290] N-(1-phenylcyclopropane-1-carbonyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl) homoserine;

[0291] N-(2-methyl-2-phenylquinolinayl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl) homoserine;

[0292] N-(1-phenylcyclobutane-1-carbonyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl) homoserine;

[0293] N-(2,2-dimethyl-3-phenylquinolinayl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl) cyclobutyl)homoserine;

[0294] N-(2-(4-fluorophenyl)-2-methylquinolinayl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl) ethyl)cyclobutyl)homoserine;

[0295] N-(3-methylaxethane-3-carbonyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl) homoserine;

[0296] N-(3-hydroxy-2,2-dimethylquinolinayl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl) cyclobutyl)homoserine;

[0297] N-(3-methoxy-2,2-dimethylquinolinayl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl) cyclobutyl)homoserine;

[0298] N-(2-methyl-2-(pyridin-3-yl)quinolinayl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2 -yl)ethyl)cyclobutyl)homoserine;

[0299] N-(2,3-dihydro-1H-indene-2-carbonyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin- 2-yl)ethyl)cyclobutyl)homoserine;

[0300] N-(3-cyano-2,2-dimethylquinolinayl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl) cyclobutyl)homoserine;

[0301] N-pivaloyl-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine;

[0302] N-(2,3-dihydro-1H-indene-1-carbonyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin- 2-yl)ethyl)cyclobutyl)homoserine;

[0303] N-((neopentyloxy)carbonyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine;

[0304] N-((1-methylcyclopropoxy)carbonyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine ;

[0305] N-((1-methylcyclobutoxy)carbonyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine ;

[0306] O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)- N-(((1,1,1- trifluoro-2-methylpropan-2-yl)oxy)carbonyl)homoserine;

[0307] N-(isopropoxycarbonyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine;

[0308] N-(diethylcarbamoyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine;

[0309] N-(tert-butylcarbamoyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine;

[0310] N-(tert-butyl(methyl)carbamoyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl) homoserine;

[0311] N-(isopropyl(methyl)carbamoyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine;

[0312] N-(di-isopropylcarbamoyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine;

[0313] N-(3,3-dimethylbutanoyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine;

[0314] N-(3-methylbutanoyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine;

[0315] N-(2-cyclobutylacetyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine;

[0316] N-(2-(1-methylcyclopropyl)acetyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl )homoserine;

[0317] N-(2-cyclopropylacetyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine;

[0318] N-(((1-(tert-butoxycarbonyl)-3-methylazetidin-3-yl)oxy)carbonyl)- O-(3-(2-(5,6,7,8-tetrahydro- 1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine;

[0319] N-(((3-methyl-1-(methylsulfonyl)azetidin-3-yl)oxy)carbonyl)-O-(3- (2-(5,6,7,8-tetrahydro-1 ,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine;

[0320] N-(((1-acetyl-3-methylazetidin-3-yl)oxy)carbonyl)-O-(3-(2- (5,6,7,8-tetrahydro-1,8- naphthyridin-2-yl)ethyl)cyclobutyl)homoserine;

[0321] N-(((3-methylazetidin-3-yl)oxy)carbonyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2- yl)ethyl)cyclobutyl)homoserine;

[0322] N-((cyclohexyloxy)carbonyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine ;

[0323] N-(isobutoxycarbonyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine;

[0324] N-(((1-(tert-butoxycarbonyl)pyrrolidin-3-yl)oxy)carbonyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8 -naphthyridin-2-yl)ethyl)cyclobutyl)homoserine;

[0325] N-((pyrrolidin-3-yloxy)carbonyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl )homoserine;

[0326] N-(4-(methylsulfonyl)butanoyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine ;

[0327] N-(((1-(methylsulfonyl)pyrrolidin-3-yl)oxy)carbonyl)-O-(3-(2- (5,6,7,8-tetrahydro-1,8-naphthyridin -2-yl)ethyl)cyclobutyl)homoserine;

[0328] N-(((1-acetylpyrrolidin-3-yl)oxy)carbonyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2- yl)ethyl)cyclobutyl)homoserine;

[0329] N-((1-phenylethoxy)carbonyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine ;

[0330] N-((2-phenylcyclobutoxy)carbonyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine ;

[0331] N-((3-phenylcyclobutoxy)carbonyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine ;

[0332] N-(((2-phenylcyclohexyl)oxy)carbonyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl) ethyl)cyclobutyl)homoserine;

[0333] 2-((tert-Butoxycarbonyl)amino)-3-methyl-4-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl) acid ethyl)cyclobutoxy)butanoic acid;

[0334] N-(((1-(tert-butoxycarbonyl)azetidin-3-yl)oxy)carbonyl)-O-(3-(2- (5,6,7,8-tetrahydro-1,8 -naphthyridin-2-yl)ethyl)cyclobutyl)homoserine;

[0335] N-(((4-phenylcyclohexyl)oxy)carbonyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl) ethyl)cyclobutyl)homoserine;

[0336] N-(((1-acetylazetidin-3-yl)oxy)carbonyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2- yl)ethyl)cyclobutyl)homoserine;

[0337] N-(((1-acetamidopropan-2-yl)oxy)carbonyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2- yl)ethyl)cyclobutyl)homoserine;

[0338] N-(((1-((tert-butoxycarbonyl)amino)propan-2-yl)oxy)carbonyl)- O-(3-(2-(5,6,7,8-tetrahydro- 1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine;

[0339] N-(((2-(3,5-dimethyl-1H-pyrazol-1-yl)cyclopentyl)oxy)carbonyl)-O- (3-(2-(5,6,7,8-tetra -hydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine;

[0340] N-(((2-(3,5-dimethyl-1H-pyrazol-1-yl)cyclohexyl)oxy)carbonyl)-O- (3-(2-(5,6,7,8 -tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine;

[0341] N-(((1-(tert-butoxycarbonyl)-3-(3-chlorophenyl)azetidin-3-yl)oxy)carbonyl)-O-(3-(2-(5,6,7,8 -tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine;

[0342] N-(((1-(tert-butoxycarbonyl)-3-(4-isopropylphenyl)azetidin-3-yl)oxy)carbonyl)-O-(3-(2-(5,6,7,8 -tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine;

[0343] N-(((1-(tert-butoxycarbonyl)-3-(phenylethynyl)azetidin-3-yl)oxy)carbonyl)-O-(3-(2-(5,6,7,8-tetra -hydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine;

[0344] N-(1-(tert-butoxycarbonyl)piperidine-4-carbonyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl )ethyl)cyclobutyl)homoserine;

[0345] N-(3,3-difluorocyclohexane-1-carbonyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl) ethyl)cyclobutyl)homoserine;

[0346] N-(2-ethyl-4,4-difluorobutanoyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl) cyclobutyl)homoserine;

[0347] N-(((2-(phenylethynyl)cyclohexyl)oxy)carbonyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2 -yl)ethyl)cyclobutyl)homoserine;

[0348] N-(4-methyltetrahydro-2H-pyran-4-carbonyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2- yl)ethyl)cyclobutyl)homoserine;

[0349] N-(2-cyclohexyl-2-methylquinolinayl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl) cyclobutyl)homoserine;

[0350] N-(2-(pyridin-2-yl)benzoyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl )cyclobutyl)homoserine;

[0351] N-(2-ethyl-4,4,4-trifluorobutanoyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl) ethyl)cyclobutyl)homoserine;

[0352] N-(2-morpholinobenzoyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine;

[0353] N-(2-ethyl-2-phenylbutanoyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl) homoserine;

[0354] N-(1H-pyrrolo[3,2-b]pyridine-7-carbonyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin- 2-yl)ethyl)cyclobutyl)homoserine;

[0355] N-(4-cyanotetrahydro-2H-pyran-4-carbonyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2- yl)ethyl)cyclobutyl)homoserine;

[0356] N-(1-(tert-butoxycarbonyl)-3-methylazetidine-3-carbonyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin- 2-yl)ethyl)cyclobutyl)homoserine;

[0357] N-(1-(tert-butoxycarbonyl)azetidine-3-carbonyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl )ethyl)cyclobutyl)homoserine;

[0358] O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)- N-(4-(trifluoromethyl)tetrahydro -2H-pyran-4-carbonyl)homoserine;

[0359] N-(1-(methylsulfonyl)piperidine-3-carbonyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl )cyclobutyl)homoserine;

[0360] O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)- N-(4,5,6,7- tetrahydro-1H-indazol-6-carbonyl)homoserine;

[0361] O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)- N-(4,5,6,7- tetrahydro-1H-indazol-7-carbonyl)homoserine;

[0362] N-(1-methyl-4,5,6,7-tetrahydro-1H-indazol-6-carbonyl)-O-(3- (2-(5,6,7,8-tetra- hydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine;

[0363] N-(1-ethyl-4,4-difluorocyclohexane-1-carbonyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin- 2-yl)ethyl)cyclobutyl)homoserine;

[0364] N-(1-(6-methylindoline-1-carbonyl)cyclopropane-1-carbonyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin -2-yl)ethyl)cyclobutyl)homoserine;

[0365] N-(4-(((tert-butoxycarbonyl)amino)methyl)tetrahydro-2H-pyran-4-carbonyl)-O-(3-(2-(5,6,7,8-tetra -hydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine;

[0366] N-(1-(pyridin-3-ylmethyl)cyclopropane-1-carbonyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2 -yl)ethyl)cyclobutyl)homoserine;

[0367] N-(3-chloro-5-methylisonicotinoyl)-O-(4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl)homoserine;

[0368] N-(4-methyltetrahydro-2H-pyran-4-carbonyl)-O-(4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl )homoserine;

[0369] N-(2,6-dichlorobenzoyl)-O-(4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl)homoserine;

[0370] N-(3,5-dichloroisonicotinoyl)-O-(4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl)homoserine;

[0371] N-(1-(4-(tert-butyl)phenyl)cyclobutane-1-carbonyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8- naphthyridin-2-yl)ethyl)cyclobutyl)homoserine;

[0372] N-(3,5-dimethylisonicotinoyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine;

[0373] N-(3-chloro-5-methylisonicotinoyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl) homoserine;

[0374] N-(3,5-dichloroisonicotinoyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine;

[0375] N-(bicyclo[2.2.2]octane-2-carbonyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl) ethyl)cyclobutyl)homoserine;

[0376] N-(2-methyl-1,2,3,4-tetrahydronaphthialene-2-carbonyl)-O-(3-(2- (5,6,7,8-tetrahydro-1, 8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine;

[0377] N-((methylsulfonyl)prolyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine;

[0378] N-(2,4-dimethylnicotinoyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine;

[0379] N-(4-phenyltetrahydro-2H-pyran-4-carbonyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2- yl)ethyl)cyclobutyl)homoserine;

[0380] N-(4-cyano-2,6-dimethylbenzoyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl) cyclobutyl)homoserine;

[0381] O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)- N-(2,4,6-trimethylpyrimidine- 5-carbonyl)homoserine;O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)-N-(2,4,6 - trimethylnicotinoyl)homoserine;

[0382] N-(3-chloro-5-fluoroisonicotinoyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl) homoserine;

[0383] N-(1-(isoquinolin-1-yl)cyclopropane-1-carbonyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2 -yl)ethyl)cyclobutyl)homoserine;

[0384] N-(2-(pyridin-2-yl)spiro[3.3]heptane-2-carbonyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8 -naphthyridin-2-yl)ethyl)cyclobutyl)homoserine;

[0385] N-(2-(1-methyl-1H-pyrazol-4-yl)tetrahydrofuran-2-carbonyl)-O-(3-(2-(5,6,7,8-tetrahydro -1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine;

[0386] N-(2,4-dimethyl-6-oxo-1,6-dihydropyridine-3-carbonyl)-O-(3-(2- (5,6,7,8-tetrahydro- 1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine;

[0387] N-(4,6-dimethylpyrimidine-5-carbonyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl) cyclobutyl)homoserine;

[0388] N-(2,6-dichloro-4-(trifluoromethyl)benzoyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl )ethyl)cyclobutyl)homoserine;

[0389] N-(1-(2-fluorophenyl)cyclopropane-1-carbonyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl )ethyl)cyclobutyl)homoserine;

[0390] N-(1-(benzo[d][1,3]dioxol-5-yl)cyclohexane-1-carbonyl)-O-(3- (2-(5,6,7,8- tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine;

[0391] N-(2,2-difluoro-1-(m-tolyl)cyclopropane-1-carbonyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8 -naphthyridin-2-yl)ethyl)cyclobutyl)homoserine;

[0392] O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)- N-(1-(tetrahydro-2H -pyran-2-yl)cyclopropane-1-carbonyl)homoserine;

[0393] N-(4-methoxy-2,6-dimethylbenzoyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl) cyclobutyl)homoserine;

[0394] N-(1-acetyl-4-(trifluoromethyl)piperidine-4-carbonyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2 -yl)ethyl)cyclobutyl)homoserine;

[0395] N-(2,3-dihydrobenzo[b][1,4]dioxin-2-carbonyl)-O-(3-(2-(5,6,7,8-tetrahydro-1 ,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine;

[0396] N-(1-(3-chlorobenzyl)cyclopentane-1-carbonyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl )ethyl)cyclobutyl)homoserine;

[0397] O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)- N-(1-(3-(trifluoromethoxy) phenyl)cyclopropane-1-carbonyl)homoserine;

[0398] N-(4-fluoro-2,6-dimethylbenzoyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl) cyclobutyl)homoserine;

[0399] N-(4-cyanotetrahydro-2H-pyran-4-carbonyl)-O-(4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl )homoserine;

[0400] O-(4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl)-N-(4-(trifluoromethyl)tetrahydro-2H-pyran- 4-carbonyl)homoserine;

[0401] N-(quinazolin-4-yl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine;

[0402] N-(8-fluoroquinazolin-4-yl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl) homoserine;

[0403] N-(7-fluoroquinazolin-4-yl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl) homoserine;

[0404] N-(7-methylquinazolin-4-yl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl) homoserine;

[0405] N-(6-fluoroquinazolin-4-yl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl) homoserine;

[0406] N-(5-fluoroquinazolin-4-yl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl) homoserine;

[0407] N-(6-methylquinazolin-4-yl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl) homoserine;

[0408] N-(6-(tert-butyl)-2-phenylpyrimidin-4-yl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin- 2-yl)ethyl)cyclobutyl)homoserine;

[0409] N-(6-(tert-butyl)pyrimidin-4-yl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl )ethyl)cyclobutyl)homoserine;

[0410] N-(2-(tert-butyl)pyrimidin-4-yl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl )ethyl)cyclobutyl)homoserine;

[0411] N-(4-(tert-butyl)pyrimidin-2-yl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl )ethyl)cyclobutyl)homoserine;

[0412] N-(8-oxabicyclo[3.2.1]octane-3-carbonyl)-O-(4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl )homoserine;

[0413] N-(2-(dimethylamino)-3,5-dimethylisonicotinoyl)-O-(4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl)homoserine ;

[0414] N-(5-chloro-2-(dimethylamino)-3-methylisonicotinoyl)-O-(4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl )homoserine;

[0415] N-(3-cyclopropyl-5-fluoroisonicotinoyl)-O-(4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl)homoserine;

[0416] N-(4-((1,3-dimethyl-1H-pyrazol-5-yl)methyl)-2,6-dimethylbenzoyl)- O-(4-(5,6,7,8-tetra- hydro-1,8-naphthyridin-2-yl)butyl)homoserine; It is

[0417] N-(5-chloro-2-methoxy-3-methylisonicotinoyl)-O-(4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl)homoserine ;

[0418] N-(3-ethyl-5-fluoroisonicotinoyl)-O-(4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl)homoserine;

[0419] N-(4-((1,3-dimethyl-1H-pyrazol-5-yl)methyl)-2-fluoro-6-methylbenzoyl)-O-(4-(5,6,7,8- tetrahydro-1,8-naphthyridin-2-yl)butyl)homoserine;

[0420] N-(3-chloro-5-fluoroisonicotinoyl)-O-(4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl)homoserine;

[0421] N-(5-fluoro-3-methylpyridazine-4-carbonyl)-O-(4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl)homoserine ;

[0422] N-(2,4-dimethyl-6-oxo-1,6-dihydropyridine-3-carbonyl)-O-(4-(5,6,7,8-tetrahydro-1,8 -naphthyridin-2-yl)butyl)homoserine;

[0423] N-(2,4-dimethyl-6-oxo-1-(2,2,2-trifluoroethyl)-1,6-dihydropyridine-3-carbonyl)-O-(4-(5,6 ,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl)homoserine;

[0424] N-(3,5-dimethylisonicotinoyl)-O-(4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl)homoserine;

[0425] N-(3,5-dimethylpyridazine-4-carbonyl)-O-(4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl)homoserine;

[0426] O-(4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl)-N-(1,2,4-trimethyl-6-oxo-1 ,6-dihydropyridine-3-carbonyl)homoserine;

[0427] N-(4-cyano-2-fluoro-6-methylbenzoyl)-O-(4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl)homoserine ;

[0428] N-(3,5-dimethylmorpholine-4-carbonyl)-O-(4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl)homoserine;

[0429] N-(5-chloro-3-methylpyridazine-4-carbonyl)-O-(4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl)homoserine ;

[0430] N-(6-methoxy-2,4-dimethylnicotinoyl)-O-(4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl)homoserine;

[0431] N-(2-chloro-4-cyano-6-fluorobenzoyl)-O-(4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl)homoserine ; It is

[0432] N-(2,6-dichlorobenzoyl)-O-(4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl)homoserine.

[0433] In one variation, the compound detailed herein is selected from the group consisting of: N-(2-chloro-3-fluorobenzoyl)-O-(4-(5,6,7,8-tetra -hydro-1,8-naphthyridin-2-yl)butyl)homoserine; N-(1-methyl-1H-indazol-4-carbonyl)-O-(4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl)homoserine; N-(4,4-difluorocyclohexane-1-carbonyl)-O-(4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl)homoserine; N-pentanoyl-O-(4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl)homoserine; N-(3-fluoro-5-(trifluoromethyl)benzoyl)-O-(4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl)homoserine; N-(3-fluoro-5-(trifluoromethyl)benzoyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl) homoserine; N-pentanoyl-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine; N-(tert-butoxycarbonyl)-O-(4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl)homoserine; N-(4-fluorobenzoyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine; N-(4-chlorobenzoyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine; N-(3-fluorobenzoyl)- O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine; N-(3-chlorobenzoyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine; N-(2-chlorobenzoyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine; N-(2-fluorobenzoyl)- O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine; N-(2,3-difluorobenzoyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine; N-(2,4-difluorobenzoyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine; N-(2-chloro-4-fluorobenzoyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine; N-(3-chloro-5-fluorobenzoyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine; N-(3-chloro-2-fluorobenzoyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine; N-(3,5-difluorobenzoyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine; N-(2,3-dichlorobenzoyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine; N-(2-chloro-6-fluorobenzoyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine; N-(2,6-difluorobenzoyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine; N-(2,5-difluorobenzoyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine; N-(3,4-dichlorobenzoyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine; N-picolinoyl-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine; N-nicotinoyl-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine; N-(1-methyl-1H-indazol-4-carbonyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl )homoserine; N-(2-methyl-2H-indazol-6-carbonyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl )homoserine; N-(2-methyl-2H-indazol-5-carbonyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl )homoserine; N-(1-methyl-1H-pyrrolo[2,3-b]pyridine-4-carbonyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin -2- yl)ethyl)cyclobutyl)homoserine; N-(2-ethylbutanoyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine; N-(1-methyl-1H-pyrrolo[2,3-b]pyridine-5-carbonyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin -2-yl)ethyl)cyclobutyl)homoserine; N-(3-(hydroxymethyl)benzoyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine; N-(quinoline-5-carbonyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine; N-(2-cyclopropylbenzoyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine; N-(quinoline-7-carbonyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine; N-(quinoline-6-carbonyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine; N-(quinoline-8-carbonyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine; N-(3-cyclopropylbenzoyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine; N-(4-cyclopropylbenzoyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine; N-isonicotinoyl-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)-homoserine; N-(3-ethylpentanoyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)-homoserine; N-(2-chloro-3-fluorobenzoyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine; N-(3,4-difluorobenzoyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine; N-(3-ethylpentanoyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine; N-isonicotinoyl-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine; O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)-N-(3-(thiazol-5-yl)benzoyl) homoserine; N-(3-hydroxy-2-phenylquinolinayl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine; N-(3-(1-methyl-1H-pyrazol-4-yl)benzoyl)-O-(3-(4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2- yl)butyl)cyclobutyl)homoserine; N-(3-(1-methyl-1H-pyrazol-4-yl)benzoyl)-O-(4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl )homoserine; N-(2-hydroxy-2-phenylacetyl)-O-(4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl)homoserine; N-(2-hydroxy-2-phenylacetyl)-O-(4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl)-homoserine; N-(2-hydroxy-2-phenylacetyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine; N-(1-phenylcyclopropane-1-carbonyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine; N-(2-methyl-2-phenylquinolinayl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine; N-(1-phenylcyclobutane-1-carbonyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine; N-(2,2-dimethyl-3-phenylquinolinayl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine ; N-(tert-butoxycarbonyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine; N-(2-(4-fluorophenyl)-2-methylquinolinayl)-O- (3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl )homoserine; N-(3-methylaxethane-3-carbonyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine; N-(3-hydroxy-2,2-dimethylquinolinayl)-O-(3-(2- (5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine ; N-(3-methoxy-2,2-dimethylquinolinayl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine ; N-(2-methyl-2-(pyridin-3-yl)quinolinayl)-O- (3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl) ethyl)cyclobutyl)homoserine; N-(2,3-dihydro-1H-indene-2-carbonyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl )ethyl)cyclobutyl)homoserine; N-(3-cyano-2,2-dimethylquinolinayl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine ; N-pivaloyl-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine; N-(2,3-dihydro-1H-indene-1-carbonyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl )ethyl)cyclobutyl)homoserine; N-((neopentyloxy)carbonyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine; N-((1-methylcyclopropoxy)carbonyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine; N-((1-methylcyclobutoxy)carbonyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine; O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)-N-(((1,1,1-trifluoro-2 -methylpropan-2-yl)oxy)carbonyl)homoserine; N-(isopropoxycarbonyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine; N-(diethylcarbamoyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine; N-(tert-butylcarbamoyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine; N-(tert-butyl(methyl)carbamoyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine; N-(isopropyl(methyl)carbamoyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine; N-(diisopropylcarbamoyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine; N-(3,3-dimethylbutanoyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine; N-(3-methylbutanoyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine; N-(2-cyclobutylacetyl)- O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine; N-(2-(1-methylcyclopropyl)acetyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine; N-(2-cyclopropylacetyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine; N-(((1-(tert-butoxycarbonyl)-3-methylazetidin-3-yl)oxy)carbonyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8 -naphthyridin-2-yl)ethyl)cyclobutyl)homoserine; N-(((3-methyl-1-(methylsulfonyl)azetidin-3-yl)oxy)carbonyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8- naphthyridin-2-yl)ethyl)cyclobutyl)homoserine; N-(((1-acetyl-3-methylazetidin-3-yl)oxy)carbonyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2 - yl)ethyl)cyclobutyl)homoserine; N-(((3-methylazetidin-3-yl)oxy)carbonyl)-O-(3- (2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl )cyclobutyl)homoserine; N-((cyclohexyloxy)carbonyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine; N-(isobutoxycarbonyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine; N-(((pyrrolidin-3- yl)oxy)carbonyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2- yl)ethyl)cyclobutyl )homoserine; N-(4-(methylsulfonyl)butanoyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine; N-(((1- (methylsulfonyl)pyrrolidin-3-yl)oxy)carbonyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2- yl)ethyl)cyclobutyl)homoserine; N-(((1-(tert-butoxycarbonyl)pyrrolidin-3-yl)oxy)carbonyl)-O-(3-(2-(5,6,7,8-tetrahydro- 1,8-naphthyridin- 2-yl)ethyl)cyclobutyl)homoserine; N-(((1-acetylpyrrolidin-3- yl)oxy)carbonyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2- yl)ethyl )cyclobutyl)homoserine; N-((1-phenylethoxy)carbonyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine; N-((2-phenylcyclobutoxy)carbonyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine; N-((3-phenylcyclobutoxy)carbonyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine; 2-((tert-butoxycarbonyl)amino)-3-methyl-4-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutoxy acid )butanoic; N-(((2-phenylcyclohexyl)oxy)carbonyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl )homoserine; N-(((1-(tert-butoxycarbonyl)azetidin-3-yl)oxy)carbonyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin- 2-yl)ethyl)cyclobutyl)homoserine; N-(((4-phenylcyclohexyl)oxy)carbonyl)-O-(3-(2- (5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl )homoserine; N-(((1-acetylazetidin-3-yl)oxy)carbonyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl )cyclobutyl)homoserine; N-(((1-((tert-butoxycarbonyl)amino)propan-2-yl)oxy)carbonyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8 -naphthyridin-2-yl)ethyl)cyclobutyl)homoserine; N-(((1-acetamidopropan-2-yl)oxy)carbonyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl )cyclobutyl)homoserine; N-(((2-(3,5-dimethyl-1H-pyrazol- 1-yl)cyclopentyl)oxy)carbonyl)-O-(3-(2-(5,6,7,8-tetrahydro- 1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine; N-(((2-(3,5-dimethyl-1H-pyrazol-1-yl)cyclohexyl)oxy)carbonyl)-O-(3-(2-(5,6,7,8-tetra- hydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)-homoserine; N-(((1-(tert-butoxycarbonyl)-3-(3-chlorophenyl)azetidin-3-yl)oxy)carbonyl)-O-(3-(2-(5,6,7,8-tetra- hydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine; N-(((1-(tert-butoxycarbonyl)-3-(4-isopropylphenyl)azetidin-3-yl)oxy)carbonyl)-O-(3-(2-(5,6,7,8-tetra- hydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine; N-(((1-(tert-butoxycarbonyl)- 3-(phenylethynyl)azetidin-3-yl)oxy)carbonyl)-O-(3-(2-(5,6,7,8-tetrahydro- 1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine; N-(1-(tert-butoxycarbonyl)piperidine-4-carbonyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl) cyclobutyl)homoserine; N-(3,3-difluorocyclohexane-1-carbonyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl )homoserine; N-(2-ethyl-4,4-difluorobutanoyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)- homoserine; N-(((2-(phenylethynyl)cyclohexyl)oxy)carbonyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl) ethyl)cyclobutyl)-homoserine; N-(2-cyclohexyl-2-methylpropanoyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine ; N-(2-(pyridin-2-yl)benzoyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl) homoserine; N-(2-ethyl-4,4,4-trifluorobutanoyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl )homoserine; N-(2-morpholinobenzoyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine; N-(2-ethyl-2-phenylbutanoyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine; N-(1H-pyrrolo[3,2-b]pyridine-7-carbonyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl )ethyl)cyclobutyl)homoserine; N-(4-cyanotetrahydro-2H-pyran-4-carbonyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl )cyclobutyl)homoserine; N-(1-(tert-butoxycarbonyl)-3-methylazetidine-3-carbonyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl )ethyl)cyclobutyl)homoserine; N-(1-(tert-butoxycarbonyl)azetidine-3-carbonyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl) cyclobutyl)homoserine; N-(1-(methylsulfonyl)piperidine-3-carbonyl)- O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl) - homoserine; O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)-N-(4,5,6,7-tetrahydro -1H-indazol-6-carbonyl)- homoserine; O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)-N-(4,5,6,7-tetrahydro -1H-indazol-7-carbonyl)homoserine; N-(4-methyltetrahydro-2H-pyran-4-carbonyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl )cyclobutyl) homoserine; N-(1-methyl-4,5,6,7-tetrahydro-1H-indazol-6-carbonyl)-O-(3-(2-(5,6,7,8-tetrahydro-1 ,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine; N-(1-ethyl-4,4-difluorocyclohexane-1-carbonyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl )ethyl)cyclobutyl)homoserine; N-(1-(6-methylindoline-1-carbonyl)cyclopropane-1-carbonyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2- yl)ethyl)cyclobutyl)homoserine; N-(4-(((tert-butoxycarbonyl)amino)methyl)tetrahydro-2H-pyran-4-carbonyl)-O-(3-(2-(5,6,7,8-tetrahydro- 1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine; N-(1-(pyridin-3-ylmethyl)cyclopropane-1-carbonyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl) ethyl)cyclobutyl)homoserine; N-(3-chloro-5-methylisonicotinoyl)-O-(4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl)homoserine; N-(4-methyltetrahydro-2H-pyran-4-carbonyl)-O-(4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl)homoserine; N-(2,6-dichlorobenzoyl)-O-(4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl)homoserine; N-(3,5-dichloroisonicotinoyl)-O-(4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl)homoserine; N-(1-(4-(tert-butyl)phenyl)cyclobutane-1-carbonyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2 -yl)ethyl)cyclobutyl)homoserine; N-(4-methyltetrahydro-2H-pyran-4-carbonyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl )cyclobutyl)homoserine; O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)-N-(4-(trifluoromethyl)tetrahydro-2H- pyran-4-carbonyl)homoserine; N-(3-chloro-5-methylisonicotinoyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine; N-(3,5-dichloroisonicotinoyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine; N-(bicyclo[2.2.2]octane-2-carbonyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl )homoserine; N-(2-methyl-1,2,3,4-tetrahydronaphthalene-2-carbonyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin -2-yl)ethyl)cyclobutyl)homoserine; N-((methylsulfonyl)prolyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine; N-(2,4-dimethylnicotinoyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine; N-(4-phenyltetrahydro-2H-pyran-4-carbonyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl )cyclobutyl)homoserine; N-(4-cyano-2,6-dimethylbenzoyl)-O-(3-(2- (5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine ; O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)-N-(2,4,6-trimethylpyrimidine-5-carbonyl )homoserine; O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)-N-(2,4,6-trimethylnicotinoyl)homoserine; N-(3-chloro-5-fluoroisonicotinoyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine; N-(1-(isoquinolin-1-yl)cyclopropane-1-carbonyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl) ethyl)cyclobutyl)homoserine; N-(2-(pyridin-2-yl)spiro[3.3]heptane-2-carbonyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin- 2-yl)ethyl)cyclobutyl)homoserine; N-(2-(1-methyl-1H-pyrazol-4-yl)tetrahydrofuran-2-carbonyl)-O-(3-(2-(5,6,7,8-tetrahydro-1, 8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine; N-(2,4-dimethyl-6-oxo-1,6-dihydropyridine-3-carbonyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8 -naphthyridin-2-yl)ethyl)cyclobutyl)homoserine; N-(4,6-dimethylpyrimidine-5-carbonyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine ; N-(2,6-dichloro-4-(trifluoromethyl)benzoyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl) cyclobutyl)homoserine; N-(1-(2-fluorophenyl)cyclopropane-1-carbonyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl) cyclobutyl)homoserine; N-(1-(benzo[d][1,3]dioxol-5-yl)cyclohexane-1-carbonyl)-O-(3-(2-(5,6,7,8-tetrahydro -1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine; N-(2,2-difluoro-1-(m-tolyl)cyclopropane-1-carbonyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin- 2-yl)ethyl)cyclobutyl)homoserine; O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)-N-(1-(tetrahydro-2H-pyran- 2-yl)cyclopropane-1-carbonyl)homoserine; N-(4-methoxy-2,6-dimethylbenzoyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine ; N-(1-acetyl-4-(trifluoromethyl)piperidine-4-carbonyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl) ethyl)cyclobutyl)homoserine; N-(2,3-dihydrobenzo[b][1,4]dioxin-2-carbonyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8- naphthyridin-2-yl)ethyl)cyclobutyl)homoserine; N-(1-(3-chlorobenzyl)cyclopentane-1-carbonyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl) cyclobutyl)homoserine; O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)-N-(1-(3-(trifluoromethoxy)phenyl)cyclopropane -1-carbonyl)homoserine; N-(4-fluoro-2,6-dimethylbenzoyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine ; N-(3,5-dimethylisonicotinoyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine; N-(2-(tert-butyl)pyrimidin-4-yl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl) cyclobutyl)homoserine; N-(4-(tert-butyl)pyrimidin-2-yl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl) cyclobutyl)homoserine; O-(3-(2-(1,8-naphthyridin-2-yl)ethyl)cyclobutyl)-N-(quinazolin-4-yl)homoserine; N-(6-(tert-butyl)pyrimidin-4-yl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl) cyclobutyl)homoserine; 2-[(4-amino-2,6-dichlorobenzoyl)amino]-4-[3-[2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl acid) )ethyl]cyclobutoxy]butanoic acid; N-(4-chloro-2,6-dimethylnicotinoyl)-O-(3-(2- (5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)- homoserine; 2-[(3-chloro-6-methyl-pyridine-2-carbonyl)amino]-4-[3-[2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2) acid -yl)ethyl]cyclobutoxy]butanoic acid; N-(2,6-dimethylpiperidine-1-carbonyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)- homoserine; N-(2,5-dimethylpyrrolidine-1-carbonyl)-O-(3- (2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)- homoserine; N-(2,6-dichloro-4-cyanobenzoyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)- homoserine; N-(2,6-dichloro-3-nitrobenzoyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)- homoserine; 4-[3-[2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl]cyclobutoxy]-2-[(1,2,4-trimethyl-6) acid -oxo-pyridine-3-carbonyl)amino]butanoic acid; N-(2-chloro-4-cyano-6-methylbenzoyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl )-homoserine; N-(3-bromo-5-chloro-2-fluoroisonicotinoyl)- O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl )- homoserine; O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)-N-(5,6,7,8-tetrahydronaphthalene -1-carbonyl)- homoserine; N-(3-bromo-2,6-dimethylbenzoyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)- homoserine; 2-[(3-chloro-5-methoxy-pyridine-4-carbonyl)amino]-4-[3-[2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2) acid -yl)ethyl]cyclobutoxy]butanoic acid; 2-[(2,6-dichloro-4-fluoro-benzoyl)amino]-4-[3-[2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl acid) )ethyl]cyclobutoxy]butanoic acid; 2-[(2-chloro-6-fluoro-benzoyl)amino]-4-[3-[2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl acid ]cyclobutoxy]butanoic acid; N-(3-bromo-2-chloro-6-fluorobenzoyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl )-homoserine; N-(2,4-dimethyl-6-oxo-1-phenyl-1,6-dihydropyridine-3-carbonyl)-O-(3-(2-(5,6,7,8-tetrahydro -1,8- naphthyridin-2-yl)ethyl)cyclobutyl)-homoserine; N-(5-bromo-2-hydroxy-isonicotinoyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)- homoserine; N-(3-chloro-5-cyclopropylisonicotinoyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)-homoserine; N-(3-chloro-5-ethylisonicotinoyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)-homoserine; N-(3-cyano-2,6-dimethylbenzoyl)-O-(3-(2- (5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)- homoserine; N-(3-bromo-5-fluoroisonicotinoyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)-homoserine; N-(2-methoxy-3,5-dimethylisonicotinoyl)-O-(3- (2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)- homoserine; N-(3-chloro-5-(trifluoromethyl)isonicotinoyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl) -homoserine; N-(3-bromo-5-chloroisonicotinoyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)-homoserine; N-(2-(dimethylamino)-3,5-dimethylisonicotinoyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl )-homoserine; N-(3-chloro-5-fluoro-2-methylisonicotinoyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl )-homoserine; N-(2,6-dichloro-3-cyanobenzoyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)- homoserine; N-(3-methyl-5-(trifluoromethyl)isonicotinoyl)- O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl) - homoserine; N-(2-hydroxy-3,5-dimethylisonicotinoyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)- homoserine; N-(3-cyano-2-hydroxy-6-methylisonicotinoyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl )-homoserine; N-(5-chloro-3-fluoro-2-methylisonicotinoyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl )-homoserine; 2-[(6-methoxy-2,4-dimethyl-pyridine-3-carbonyl)amino]-4-[3-[2-(5,6,7,8-tetrahydro-1,8-naphthyridin) acid -2-yl)ethyl]cyclobutoxy]butanoic acid; 2-[[2,6-dimethyl-4-[(4-methylpiperazin-1-yl)methyl]benzoyl]amino]-4-[3-[2-(5,6,7,8-tetrahydro acid) -1,8-naphthyridin-2-yl)ethyl]cyclobutoxy]butanoic acid; N-(3,5-dimethylmorpholine-4-carbonyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)- homoserine; 2-[[5-chloro-3-fluoro-2-[(4-methylpiperazin-1-yl)methyl]pyridine-4-carbonyl]amino]-4-[3-[2-(5,6,7) acid ,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl]cyclobutoxy]butanoic acid; 2-[(7-chloro-5-oxo-2,3-dihydro-1H-indolizine-8-carbonyl)amino]-4-[3-[2-(5,6,7,8-tetra- methyl hydro-1,8-naphthyridin-2-yl)ethyl]cyclobutoxy]butanoate; 2-[(2,6-difluoro-4-hydroxy-benzoyl)amino]-4-[3-[2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl acid) )ethyl]cyclobutoxy]butanoic acid; 2-[(4-chloro-2-methyl-pyrazol-3-carbonyl)amino]-4-[3-[2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2) acid - yl)ethyl]cyclobutoxy]butanoic acid; 2-[(2-methylpyrazol-3-carbonyl)amino]-4-[3-[2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl]cyclobutoxy acid ]butanoic; N-(1-(phenylsulfonyl)piperidine-2-carbonyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl) -homoserine; 2-(3,3-dimethylbutanoylamino)-4-[3-[2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl]cyclobutoxy]butanoic acid; 2-[(2-phenylacetyl)amino]-4-[3-[2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl]cyclobutoxy]butanoic acid; 4-[3-[2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl]cyclobutoxy]-2-[(4,4,4-trifluoro-3) acid ,3-dimethyl-butanoyl)amino]butanoic acid; 2-[(4,4-difluoro-3,3-dimethyl-butanoyl)amino]-4-[3-[2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2) acid - yl)ethyl]cyclobutoxy]butanoic acid; 2-[[2-phenylpropanoyl]amino]-4-[3-[2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl]cyclobutoxy]butanoic acid; 2-[[2-(3,5-difluorophenyl)acetyl]amino]-4-[3-[2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl) acid ethyl]cyclobutoxy]butanoic acid; 2-[[2-(tert-butoxycarbonylamino)-1-methyl-ethoxy]carbonylamino]-4-[3-[2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2) acid -yl)ethyl]cyclobutoxy]butanoic acid; 2-[(3,6-dimethylpyridine-2-carbonyl)amino]-4-[3-[2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl acid ]cyclobutoxy]butanoic acid; 2-[(6-fluorochromano-2-carbonyl)amino]-4-[3-[2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl]cyclobutoxy acid ]butanoic; 4-[3-[2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl]cyclobutoxy]-2-[2-[3-(trifluoromethyl)phenyl] acid butanoylamino]butanoic acid; 2-[(3-chloro-5-methyl-pyridine-4-carbonyl)amino]-4-[3-[2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2) acid - yl)ethyl]cyclobutoxy]butanoic acid; 2-[(3-chloro-5-fluoro-pyridine-4-carbonyl)amino]-4-[3-[2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2) acid - yl)ethyl]cyclobutoxy]butanoic acid; 2-[(4-cyano-2,6-dimethyl-benzoyl)amino]-4-[3-[2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl acid) )ethyl]cyclobutoxy]butanoic acid; 2-[[4-(2-chlorophenyl)tetrahydropyran-4-carbonyl]amino]-4-[3-[2-(5,6,7,8-tetrahydro-1,8-naphthyridin-) acid 2-yl)ethyl]cyclobutoxy]butanoic acid; 2-[(2-hydroxy-indane-2-carbonyl)amino]-4-[3-[2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl acid ]cyclobutoxy]butanoic acid; 2-[(1-cyclopropylcyclopropanecarbonyl)amino]-4-[3-[2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl]cyclobutoxy]butanoic acid; 2-[[3-(difluoromethyl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyridine-6-carbonyl]amino]-4-[ acid 3-[2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl]cyclobutoxy]butanoic acid; 2-[(1-cyclopropylcyclobutanecarbonyl)amino]-4-[3-[2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl]cyclobutoxy]butanoic acid; 2-[[1-(4-isopropylphenyl)cyclopentanecarbonyl]amino]-4-[3-[2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl] acid cyclobutoxy]butanoic acid; 2-(bicyclo[2.2.2]octane-4-carbonylamino)-4-[3-[2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl] acid cyclobutoxy]butanoic acid; 2-(3,4,5,6,7,7a-hexahydro-2H-benzofuran-3a-carbonylamino)-4-[3-[2-(5,6,7,8-tetrahydro-) acid 1,8-naphthyridin-2-yl)ethyl]cyclobutoxy]butanoic acid; 2-[[1-(2-phenylethyl)cyclopropanecarbonyl]amino]-4-[3-[2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl] acid cyclobutoxy]butanoic acid; 2-[[4-(3-methylisoxazol-5-yl)tetrahydropyran-4-carbonyl]amino]-4-[3-[2-(5,6,7,8-tetrahydro-1) acid, 8-naphthyridin-2-yl)ethyl]cyclobutoxy]butanoic acid; 2-[[1-(benzenesulfonyl)cyclopropanecarbonyl]amino]-4-[3-[2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl]cyclobutoxy acid] butanoic; 2-[(1-phenylcycloheptanecarbonyl)amino]-4-[3-[2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl]cyclobutoxy]butanoic acid ; 2-[(4-methylsulfonyltetrahydropyran-4-carbonyl)amino]-4-[3-[2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl acid ]cyclobutoxy]butanoic acid; 2-[[1-(4-sulfamoylphenyl)cyclopropanecarbonyl]amino]-4-[3-[2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl] acid cyclobutoxy]butanoic acid; N-((phenylsulfonyl)prolyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)-homoserine; N-(5-chloro-3-fluoro-2-((4-methylpiperazin-1-yl)methyl)isonicotinoyl)-O-(3-(2-(5,6,7,8-tetrahydro-1 ,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine; N-(3-chloro-5-fluoro-2-((4-methylpiperazin-1-yl)methyl)isonicotinoyl)-O-(3-(2- (5,6,7,8-tetrahydro-1 ,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine; 2-(pyrimidin-4-ylamino)-5-(3-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)propoxy)pentanoic acid; 2-[(3-chloro-5-methyl-pyridine-4-carbonyl)amino]-4-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl) acid butoxy]butanoic acid; 2-[(2,4-dimethylpyridin-3-carbonyl)amino]-4-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butoxy]butanoic acid; 2-[(4-cyano-2,6-dimethyl-benzoyl)amino]-4-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butoxy acid] butanoic; 2-[(3,5-dichloropyridin-4-carbonyl)amino]-4-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butoxy]butanoic acid; 2-[(3-chloro-5-fluoro-pyridine-4-carbonyl)amino]-4-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl) acid butoxy]butanoic acid; N-(3,5-dimethylmorpholine-4-carbonyl)-O-(4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl)-homoserine; N-(2,6-dichlorobenzoyl)-O-(4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl)-homoserine; N-(3,5-dimethylisonicotinoyl)-O-(4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl)-homoserine; 2-[(2,4-dichloro-6-fluoro-benzoyl)amino]-4-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butoxy acid] butanoic; 2-[(2,4-dimethyl-6-oxo-1H-pyridine-3-carbonyl)amino]-4-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin- acid) 2-yl)butoxy]butanoic acid; N-(3-chloro-5-methoxy-isonicotinoyl)-O-(4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl)-homoserine; 2-[(2-chloro-6-fluoro-benzoyl)amino]-4-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butoxy]butanoic acid; N-(tert-butoxycarbonyl)-O-(4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl)-homoserine; N-(5-bromo-2-hydroxy-isonicotinoyl)-O-(4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl)-homoserine; N-(3-bromo-5-chloro-2-fluoroisonicotinoyl)-O-(4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl)-homoserine; N-(2,4-dimethyl-6-oxo-1-phenyl-1,6-dihydropyridine-3-carbonyl)-O-(4-(5,6,7,8-tetrahydro-1, 8-naphthyridin-2-yl)butyl)-homoserine; O-(4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl)-N-(5,6,7,8-tetrahydronaphthalene-1-carbonyl) -homoserine; N-(3-bromo-2,6-dimethylbenzoyl)-O-(4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl)-homoserine; N-(3-chloro-5-fluoroisonicotinoyl)-O-(4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl)-homoserine; N-(3-bromo-2-chloro-6-fluorobenzoyl)-O-(4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl)-homoserine; 2-[(3-chloro-5-methoxy-pyridine-4-carbonyl)amino]-4-[2-methyl-4-(5,6,7,8-tetrahydro-1,8-naphthyridin-) acid 2-yl)butoxy]butanoic acid; 2-[(3-chloro-5-fluoro-pyridine-4-carbonyl)amino]-4-[2-methyl-4-(5,6,7,8-tetrahydro-1,8-naphthyridin- acid) 2-yl)butoxy]butanoic acid; N-(3-chloro-5-fluoroisonicotinoyl)-O-(2-methyl-4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl)-homoserine; N-(2,6-dichlorobenzoyl)-O-(2-methyl-4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl)-homoserine; N-(2-chloro-6-fluorobenzoyl)-O-(2-methyl-4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl)-homoserine; N-(4-fluoro-2-methylnicotinoyl)-O-(2-methyl-4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl)-homoserine; 2-[(3-chloro-5-fluoro-pyridine-4-carbonyl)amino]-4-[2-hydroxy-4-(5,6,7,8-tetrahydro-1,8-naphthyridin-) acid 2-yl)butoxy]butanoic acid; 2-(1-methyl-1H-indazol-4-carboxamido)-5-(3-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)propoxy)pentanoic acid; 2-(3-(1-methyl-1H-pyrazol-4-yl)benzamido)-5-(3-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl) acid propoxy)pentanoic; 2-(2-chloro-3-fluorobenzamido)-6-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethoxy)hexanoic acid; 2-(3-(1-methyl-1H-pyrazol-4-yl)benzamido)-6-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl) acid ethoxy)hexanoic; 2-(2-ethylbutanamido)-6-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethoxy)hexanoic acid; 2-(1-methyl-1H-indazol-4-carboxamido)-6-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethoxy)hexanoic acid; 2-((tert-butoxycarbonyl)amino)-5-(3-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)propoxy)pentanoic acid; N-benzoyl-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine; N-(quinazolin-4-yl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine; N-(8-fluoroquinazolin-4-yl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine; N-(7-fluoroquinazolin-4-yl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine; N-(7-methylquinazolin-4-yl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine; N-(6-fluoroquinazolin-4-yl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine; N-(5-fluoroquinazolin-4-yl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine; N-(6-methylquinazolin-4-yl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine; and N-(6-(tert-butyl)-2-phenylpyrimidin-4-yl)-O- (3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2- yl)ethyl)cyclobutyl)-homoserine.

[0434] In some embodiments, a composition is provided, such as a pharmaceutical composition, wherein the composition comprises a compound selected from the group consisting of one or more of the compounds in Table 1, or a stereoisomer thereof (including a mixture of two or more stereoisomers thereof), or a salt thereof. In some embodiments, the composition comprises a compound selected from the group consisting of a salt of one or more of the compounds depicted in Table 1. In one aspect, the composition is a pharmaceutical composition that further comprises a pharmaceutically acceptable carrier.

[0435] In some embodiments, a composition is provided, such as a pharmaceutical composition, wherein the composition comprises a compound selected from the group consisting of one or more of the compounds depicted in Table 2, or a stereoisomer thereof (including a mixture of two or more stereoisomers thereof), or a salt thereof. In some embodiments, the composition comprises a compound selected from the group consisting of a salt of one or more of the compounds depicted in Table 2. In one aspect, the composition is a pharmaceutical composition that further comprises a pharmaceutically acceptable carrier.

[0436] The invention also includes all salts of the compounds referred to herein, such as pharmaceutically acceptable salts. The invention also includes any or all stereochemical forms, including any enantiomeric or diastereomeric forms and any tautomers or other forms of the described compounds. Unless stereochemistry is explicitly indicated in a chemical structure or name, the structure or name is intended to encompass all possible stereoisomers of a represented compound. Furthermore, where a specific stereochemical form is represented, it is understood that other stereochemical forms are also described and encompassed by the invention. All forms of the compounds are also encompassed by the invention, such as crystalline or non-crystalline forms of the compounds. It is also understood that prodrugs, solvates and metabolites of the compounds are covered by this disclosure. Compositions comprising a compound of the invention are also intended as a composition of a substantially pure compound, including a specific stereochemical form thereof. Compositions comprising a mixture of compounds of the invention in any ratio are also encompassed by the invention, including mixtures of two or more stereochemical forms of a compound of the invention in any ratio, such that racemic, non-racemic, enantioenriched and scalemic mixtures of a compound are embraced. When one or more tertiary amine chemical moieties are present in the compound, N-oxides are also provided and described.

[0437] The compounds described in this document are inhibitors of integrin αvβ6. In some cases, it is desirable for the compound to inhibit integrins other than integrin αvβ6. In some embodiments, the compound inhibits integrin αvβ6 and one or more of integrin αVβ1, αVβ3, αVβ5, α2β1, α3β1, α6β1, α7β1 and α11β1. In some embodiments, the compound inhibits αvβ6 integrin and αvβ1 integrin. In some embodiments, the compound inhibits αvβ6 integrin, αvβ3 integrin and αvβ5 integrin. In some embodiments, the compound inhibits αvβ6 integrin and α2β1 integrin. In some embodiments, the compound inhibits αvβ6 integrin, α2β1 integrin and α3β1 integrin. In some embodiments, the compound inhibits αvβ6 integrin and α6β1 integrin. In some embodiments, the compound inhibits αvβ6 integrin and α7β1 integrin. In some embodiments, the compound inhibits αvβ6 integrin and α11β1 integrin.

[0438] In some cases, it is desirable to avoid inhibition of other integrins. In some embodiments, the compound is a selective inhibitor of integrin αvβ6. In some embodiments, the compound does not substantially inhibit integrin α4β1, αvβ8 and/or α2β3. In some embodiments, the compound inhibits αvβ6 integrin, but does not substantially inhibit α4β1 integrin. In some embodiments, the compound inhibits αvβ6 integrin, but does not substantially inhibit αvβ8 integrin. In some embodiments, the compound inhibits αvβ6 integrin, but does not substantially inhibit α2β3 integrin. In some embodiments, the compound inhibits αvβ6 integrin, but does not substantially inhibit αvβ8 integrin and α4β1 integrin.

[0439] The invention also envisages isotopically labeled and/or isotopically enriched forms of compounds described herein. Compounds herein may contain unnatural ratios of atomic isotopes in one or more of the atoms constituting such compounds. In some embodiments, the compound is isotopically labeled, such as an isotopically labeled compound of formula (I) or variations thereof described herein, in which one or more atoms are replaced by an isotope of the same element. Exemplary isotopes that can be incorporated into compounds of the invention include isotopes of hydrogen, carbon, nitrogen, oxygen, phosphorus, sulfur, chlorine, such as 2H, 3H, 11C, 13C, 14C, 13N, 15O, 17O, 32P, 35S, 18F, 36Cl. Incorporation of heavier isotopes, such as deuterium (2H or D), may provide certain therapeutic advantages resulting from greater metabolic stability, e.g., increased in vivo half-life or reduced dosage requirements, and therefore may be preferred in some cases. . In some embodiments, an isotopically enriched form of any of the formulas described herein is provided herein, wherein the compound comprises one or more deuterium atoms. In some embodiments, the compounds of formula (I) may have one or more of the hydrogen atoms replaced by deuterium, such as any of the hydrogens in one or more of the G, L1, L2, Y, L3, and R1 moieties.

[0440] The isotopically labeled compounds of the present invention can generally be prepared by standard methods and techniques known to those skilled in the art or by procedures similar to those described in the accompanying Examples, substituting appropriate isotopically labeled reagents in place of the corresponding unlabeled reagent.

[0441] The invention also includes any or all metabolites of any of the described compounds. Metabolites may include any chemical species generated by a biotransformation of any of the described compounds, such as intermediates and products of the compound's metabolism.

[0442] Articles of manufacture comprising a compound of the invention, or a salt or solvate thereof, in a suitable container are provided. The container may be a vial, jug, ampoule, pre-filled syringe, i.v. bag, and the like.

[0443] Preferably, the compounds detailed in this document are orally bioavailable. However, the compounds can also be formulated for parenteral (e.g., intravenous) administration.

[0444] One or more compounds described herein can be used in the preparation of a medicament by combining the compound or compounds as an active ingredient with a pharmacologically acceptable carrier, which are known in the art. Depending on the therapeutic form of the drug, the vehicle can have several forms. GENERAL SYNTHETIC METHODS

[0445] The compounds of the invention can be prepared by a series of processes as generally described below and more specifically in the following Examples (such as the schemes provided in the Examples below). In the following process descriptions, symbols when used in the formulas depicted are to be understood as representing those groups described above in relation to the formulas herein.

[0446] When it is desired to obtain a particular stereoisomer of a compound, this can be accomplished from a corresponding mixture of stereoisomers using any conventional procedure suitable for separating or resolving stereoisomers. Thus, for example, diastereomeric derivatives can be produced by reacting a mixture of enantiomers, for example, a racemate and an appropriate chiral compound. The diastereomers can then be separated by any convenient means, for example by crystallization, and the desired enantiomer recovered. In another resolution process, a racemate can be separated using chiral high-performance liquid chromatography. Alternatively, if desired, a particular stereoisomer can be obtained using an appropriate chiral intermediate in one of the processes described.

[0447] Chromatography, recrystallization and other conventional separation procedures can also be used with intermediates or final products where it is desired to obtain a particular isomer of a compound or otherwise purify a product of a reaction.

[0448] Solvates and/or polymorphs of a compound provided herein or a pharmaceutically acceptable salt thereof are also contemplated. Solvates contain stoichiometric or nonstoichiometric amounts of a solvent and are often formed during the crystallization process. Hydrates are formed when the solvent is water, or alcoholates are formed when the solvent is alcohol. Polymorphs include the different crystal packing arrangements of the same elemental composition of a compound. Polymorphs generally have different X-ray diffraction patterns, infrared spectrum, melting points, density, hardness, crystal shape, optical and electrical properties, stability and/or solubility. Various factors, such as the recrystallization solvent, rate of crystallization, and storage temperature, can cause a single crystal form to dominate.

[0449] The compounds provided herein can be prepared according to General Schemes A, B, C, D-2, E-2, F-2, G-2 and H; Schemes D-1, E-1, F-1 and G-1; General Procedures A, B, C, D, E, F, G, H, I, J, K, L, M, N, O, P, Q and R; and Examples 1 to 226.

[0450] Compounds of formula 18A can be prepared according to general Scheme A, wherein G, R2 and R3 are as defined for formula (I), or any applicable variations detailed herein; X1 is a leaving group (e.g. -OH, -Cl, 0and similar); and X2 is another leaving group (e.g., -Cl, -Br, -I, -OTf, and the like). GENERAL SCHEME A

[0451] Silylation of compound 1A generates compound 2A, which can be reduced with a suitable reducing agent to generate compound 3A. Iodination of 3A generates compound 4A, which can be alkylated with compound 5A under basic conditions to generate compound 6A. Condensation of compound 6A with compound 7A in the presence of a suitable catalyst generates compound 8A, which can be alkylated with an alkyl halide to generate compound 9A. Oxidative cleavage of 9A generates compound 10A, which can be treated with compound 11A under basic conditions to obtain compound 12A. Reduction of compound 12A generates compound 13A, which can be exposed to an appropriate acid to generate compound 14A. Coupling compound 14A with the compound of formula 15A or 16A gives rise to compound 17A, which can be hydrolyzed in the presence of a suitable hydroxide source to generate compound 18A.

[0452] The reaction conditions for the transformations of General Scheme A are provided in the following General Procedures, in particular General Procedures D, E, F, H, I, K and N. Exemplary reaction conditions for the transformations of General Scheme A are provided in General Procedure A, omitting the chiral separation step at the end of General Procedure A.

[0453] Compounds of formula 18B can be prepared according to General Scheme B, wherein G, R2 and R3 are as defined for formula (I) or any applicable variations detailed herein; X1 is a leaving group (e.g. -OH, -Cl, 0and similar); and X2 is another leaving group (e.g. -Cl, -Br, -I, -OTf and the like). GENERAL SCHEME B

[0454] Silylation of compound 1B generates compound 2B, which can be reduced with a suitable reducing agent to generate compound 3B. Iodination of 3B generates compound 4B, which can be alkylated with compound 5A under basic conditions to generate compound 6B. Condensation of compound 6B with compound 7A in the presence of a suitable catalyst generates compound 8B, which can be alkylated with an alkyl halide to generate compound 9B. Oxidative cleavage of 9B generates compound 10B, which can be treated with compound 11A under basic conditions to obtain compound 12B. Reduction of compound 12B generates compound 13B, which can be exposed to an appropriate acid to generate compound 14B. Coupling compound 14B with the compound of formula 15A or 16A gives compound 17B, which can be hydrolyzed in the presence of a suitable hydroxide source to generate compound 18B.

[0455] Reaction conditions for the transformations of General Scheme B are provided in the following General Procedures, in particular, General Procedures D, E, F, H, I, K and N. Exemplary reaction conditions for the transformations of General Scheme B are provided in General Procedure B, omitting the chiral separation step at the end of General Procedure B.

[0456] Compounds of formula 12C can be prepared according to general Scheme C, wherein G, R2 and R3 are as defined for formula (I), or any applicable variations detailed herein; X 1 is a leaving group (for example, -OH, -Cl, 0and similar); and X2 is another leaving group (-e.g., -Cl, -Br, -I, -OTf and the like). GENERAL SCHEME C

[0457] Reduction of compound 1C generates compound 2C, which can be alkylated with an alkyl halide to generate compound 3C. Oxidative cleavage of 3C generates compound 4C, which can be treated with compound 11A under basic conditions to generate compound 6C. Reduction of compound 6C generates compound 7C, which can be exposed to an appropriate acid to generate compound 8C. Coupling the compound 8C with the compound of formula 15A or 16A gives rise to the compound of formula 11C, which can be hydrolyzed in the presence of a suitable hydroxide source to generate compound 12C.

[0458] The reaction conditions for the transformations of General Scheme C are provided in the following General Procedures, in particular General Procedures D, E, F, H, I, K and N. Exemplary reaction conditions for the transformations of General Scheme C are provided in General Procedure C, omitting the chiral separation step at the end of General Procedure C.

[0459] Compounds of formula 18D may be prepared according to Scheme D-1, followed by General Scheme D-2, wherein G, R2, and R3 are as defined for formula (I), or any applicable variations detailed herein document; X1 is a leaving group (e.g. -OH, -Cl, and the like); and X2 is another leaving group (e.g. -Cl, -Br, -I, -OTf and the like). D-1 SCHEME

[0460] Silylation of compound 1A generates compound 2A, which can be reduced with a suitable reducing agent to generate compound 3A. Iodination of 3A generates compound 4A, which can be alkylated with compound 5A under basic conditions to generate compound 6A. Condensation of compound 6A with compound 7A in the presence of a suitable catalyst generates compound 8A, which can be alkylated with an alkyl halide to generate compound 9A. Oxidative cleavage of 9A generates compound 10A, which can be treated with compound 11A under basic conditions to obtain compound 12A. Reduction of compound 12A generates compound 13A, which can be separated using chiral SFC to obtain Isomer D1 and Isomer D2. GENERAL SCHEME D-2

[0461] Exposure of Isomer D1 (i.e., first eluting isomer of Scheme D-1) or Isomer D2 (i.e., second eluting isomer of Scheme D-1) to an appropriate acid generates compound 14D, wherein The wavy line in compound 14D refers to the isomer obtained when either the D1 Isomer or the D2 Isomer is reacted. Coupling the compound 14D with the compound of formula 15A or 16A gives rise to the compound 17D, which can be hydrolyzed in the presence of a suitable hydroxide source to generate the compound 18D.

[0462] Reaction conditions for the transformations of General Scheme D-2 are provided in the following General Procedures, in particular General Procedures D, E, F, H, I, K and N. Exemplary reaction conditions for the transformations of Scheme D-1 are given in General Procedure A.

[0463] Compounds of structural formula 18E may be prepared according to Scheme E-1 followed by general Scheme E-2, wherein G, R2, and R3 are as defined for formula (I), or any applicable variations detailed herein document; X1 is a leaving group (e.g. -OH, -Cl, 0 and similar); and X2 is another leaving group (e.g. -Cl, -Br, -I, -OTf and the like). SCHEME E-1

[0464] Silylation of compound 1B generates compound 2B, which can be reduced with a suitable reducing agent to generate compound 3B. Iodination of 3B generates compound 4B, which can be alkylated with compound 5A under basic conditions to generate compound 6B. Condensation of compound 6B with compound 7A in the presence of a suitable catalyst generates compound 8B, which can be alkylated with an alkyl halide to generate compound 9B. Oxidative cleavage of 9B generates compound 10B, which can be treated with compound 11A under basic conditions to obtain compound 12B. Reduction of compound 12B generates compound 13B, which can be separated using supercritical fluid chromatography (SFC) into Isomer E1 and Isomer E2. GENERAL SCHEME E-2

[0465] Exposure of Isomer E1 (i.e., first eluting isomer of Scheme E-1) or Isomer E2 (i.e., second eluting isomer of Scheme E-1) to an appropriate acid generates compound 14E, wherein the wavy line in compound 14E refers to the isomer obtained when the E1 Isomer or the E2 Isomer is reacted. Coupling the compound 14E with the compound of formula 15A or 16A gives rise to the compound 17E, which can be hydrolyzed in the presence of a suitable hydroxide source to generate the compound 18E.

[0466] Reaction conditions for the transformations of General Scheme E-2 are provided in the following General Procedures, in particular General Procedures D, E, F, H, I, K and N. Exemplary reaction conditions for the transformations of Scheme E-1 are given in General Procedure B.

[0467] Compounds of formula 12F may be prepared according to Scheme F-1 followed by General Scheme F-2, wherein G, R2, and R3 are as defined for formula (I), or any applicable variations detailed herein. ; X1 is a leaving group (e.g. -OH, -Cl, 0 and similar); and X2 is another leaving group (e.g. -Cl, -Br, -I, -OTf and the like). F-1 SCHEME

[0468] Reduction of compound 1C generates compound 2C, which can be alkylated with an alkyl halide to generate compound 3C. Oxidative cleavage of 3C generates compound 4C, which can be treated with compound 11A under basic conditions to generate compound 6C. Reduction of compound 6C generates compound 7C, which can be separated using supercritical fluid chromatography (SFC) into Isomer F1 and Isomer F2. GENERAL SCHEME F-2

[0469] Exposure of Isomer F1 (i.e., first eluting isomer of Scheme F-1) or Isomer F2 (i.e., second eluting isomer of Scheme F-1) to an appropriate acid generates compound 8F, wherein The wavy line in compound 8F refers to the isomer obtained when Isomer F1 or Isomer F2 is reacted. Coupling the compound 8F with the compound of formula 15A or 16A gives rise to the compound of formula 11F, which can be hydrolyzed in the presence of a suitable hydroxide source to generate compound 12F.

[0470] Reaction conditions for the transformations of General Scheme F-2 are provided in the following General Procedures, in particular General Procedures D, E, F, H, I, K and N. Exemplary reaction conditions for the transformations of Scheme F-1 are given in General Procedure C.

[0471] Compounds of formula 18G can be prepared according to Scheme G-1 followed by General Scheme G-2, wherein G, R2 and R3 are as defined for formula (I), or any applicable variations detailed herein ; Is X1 an Ox V leaving group? (e.g. -OH, -Cl, 0 and similar); and X2 is another leaving group (e.g. -Cl, -Br, -I, -OTf and the like). G-1 SCHEME

[0472] Silylation of compound 1A generates compound 2A, which can be reduced with a suitable reducing agent to generate compound 3A. Iodination of 3A generates compound 4A, which can be alkylated with compound 5A under basic conditions to generate compound 6A. Condensation of compound 6A with compound 7A in the presence of a suitable catalyst generates compound 8A, which can be alkylated with an alkyl halide to generate compound 9A. Oxidative cleavage of 9A generates compound 10A, which can be treated with compound 11A under basic conditions to obtain compound 12A. Reduction of compound 12A generates compound 13A, which can be exposed to an appropriate acid to generate compound 14A. Compound 14A can be separated using chiral SFC to give the G1 isomer and the G2 isomer. GENERAL SCHEME G-2

[0473] Coupling the G1 isomer elution of Scheme G-1) or Isomer G2 (i.e. second elution isomer of Scheme G-1) with the compound of formula 15A or 16A generates the compound 17G, in which the wavy line in compound 17G refers to the isomer obtained when the G1 isomer or the G2 isomer is reacted. Compound 17G can be hydrolyzed in the presence of a suitable hydroxide source to generate compound 18G.

[0474] The reaction conditions for the transformations of Scheme G-1 and General Scheme G-2 are provided in the following General Procedures, in particular General Procedures D, E, F, H, I, K and N. Exemplary reaction conditions for the transformations of Scheme G-1 are provided in General Procedure A.

[0475] Compounds of formula 18H can be prepared according to General Scheme H, wherein G, R2 and R3 are as defined for formula (I) or any applicable variations detailed herein; X1 is a leaving group (e.g. -OH, -Cl, °\^ and the like); and X2 is another leaving group (e.g. -Cl, -Br, -I, -OTf and the like). GENERAL SCHEME H

[0476] Allylation of compound 1A generates compound 2H, which can be reduced with a suitable reducing agent to generate compound 3H. Iodination of 3H generates the compound 4H, which can be alkylated with the compound 5A under basic conditions to generate the compound 6H. Condensation of compound 6H with compound 7A in the presence of a suitable catalyst generates compound 9H, which can be alkylated with an alkyl halide to generate compound 9H. Oxidative cleavage of 9H followed by treatment with compound 11A under basic conditions provides compound 12H. Reduction of compound 12H generates compound 13H, which can be exposed to an appropriate acid to generate compound 14H. Coupling the compound 14H with the compound of formula 15A or 16A gives rise to the compound 17H, which can be hydrolyzed in the presence of a suitable hydroxide source to generate the compound 18H.

[0477] The reaction conditions for the transformations of General Scheme H are provided in the following General Procedures, in particular General Procedures D, E, F, H, I, K and N.

[0478] It is understood that the above schemes can be modified to arrive at various compounds of the invention by selecting appropriate reagents and starting materials. For a general description of protective groups and their use, see PGM Wuts and TW Greene, Greene's Protective Groups in Organic Synthesis 4th edition, Wiley-Interscience, New York, 2006.

[0479] Additional methods of preparing compounds according to formula (I), and salts thereof, are provided in the Examples. As one skilled in the art would recognize, the preparation methods taught herein can be adapted to provide additional compounds within the scope of formula (I), for example, by selecting starting materials that would provide a desired compound.

PHARMACEUTICAL COMPOSITIONS AND FORMULAS

[0480] Pharmaceutical compositions of any of the compounds detailed in this document, including compounds of formulas (I), (IIa), (IIb), (IIIa), (IIIb), (IVa), (IVb), (Va) , (Va-1), (Va-2), (Vb), (Vb-1) and (Vb-2), or a salt thereof, or compounds represented in Table 1, or a salt thereof, or mixtures of the same, are covered by this invention. Thus, the invention includes pharmaceutical compositions comprising a compound of the invention or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier or excipient. In one aspect, the pharmaceutically acceptable salt is an acid addition salt, such as a salt formed with an inorganic or organic acid. The pharmaceutical compositions according to the invention may take a form suitable for oral, buccal, parenteral, nasal, topical or rectal administration or a form suitable for administration by inhalation. In one embodiment, the pharmaceutical composition is prepared from mixtures of any of the compounds detailed herein, or salts thereof. In one embodiment, the pharmaceutical composition is a composition for controlled release of any of the compounds detailed herein.

[0481] Pharmaceutical compositions of any of the compounds detailed in this document, including compounds of formulas (I), (IIa), (IIb), (IIIa), (IIIb), (IVa), (IVb), (Va) , (Va-1), (Va-2), (Vb), (Vb-1), (Vb-2), (II-A-1), (II-A-2), (II-A- 2i), (II-A-2ii), (II-A-1a-1), (II-A-1a-2), (II-A- 1a-3), (II-A-1b-1) , (II-A-1b-2), (II-A-1c-1), (II-A-1c-2), (II-A-1d-1), (II-A-1d- 2) , (II-A-1d-3), (II-A-2a-1), (II-A-2a-2), (II-A-2a-3), (II-A-2a-4) , (II-A-2b-1), (II-A-2b-2), (II-A-2c-1), (II-A-2c-2), (II-A-2c-3) , (II-A-2c-4), (II-A-2d-1), (II-A-2d-2), (II-A-2d-3), (II-A-2d-4) , (II-A-2d-5), (II-A-2d-6), (II-A-2e-1), (II-A- 2e-2), (II-A-2e-3) , (II-A-2e-4), (II-A-2e-5), (II-A-2e-6), (II-A-2e-7), (II-A- 2e-8) , (II-A-2f-1), (II-A-2f-2), (II-A-2f-3), (II-A-2f-4), (II-A-2f-5) , (II-A-2f-6), (II-A-2f-7), (II-A-2f-8), (II-A-2f-9), (II-A-2f-10) , (II-B-1), (II-B-2), (II-B-3), (II-B-1a), (II-B-2a), (II-B-2b), ( II-B-3a) or (II-B-3b), a compound of Table 1 or Table 2, or any of compounds 1 to 329; or a salt thereof, or mixtures thereof, are also encompassed by this invention.

[0482] A compound as detailed herein may, in one aspect, be in a purified form, and compositions comprising a compound in purified forms are detailed herein. In one embodiment, the compositions may have no more than 35% impurity, wherein the impurity denotes a compound other than the compound comprising the majority of the composition or a salt thereof, e.g., a composition of a compound selected from of a Table 1 compound may contain no more than 35% impurity, wherein the impurity denotes a compound other than the Table 1 compound or a salt thereof. In one embodiment, the compositions may contain no more than 25% impurity. In one embodiment, the compositions may contain no more than 20% impurity. In still other embodiments, compositions comprising a compound as detailed herein or a salt thereof are provided as compositions of substantially pure compounds. "Substantially pure" compositions comprise no more than 10% impurity, such as a composition comprising less than 9%, 7%, 5%, 3%, 1% or 0.5% impurity. In some embodiments, a composition containing a compound as detailed herein or a salt thereof is in substantially pure form. In yet another variation, a substantially pure compound composition or a salt thereof is provided wherein the composition does or does not contain more than 10% impurity. In another variation, a substantially pure compound composition or a salt thereof is provided, wherein the composition does or does not contain more than 9% impurity. In another variation, a substantially pure compound composition or a salt thereof is provided, wherein the composition does or does not contain more than 7% impurity. In another variation, a substantially pure compound composition or a salt thereof is provided, wherein the composition does or does not contain more than 5% impurity. In another variation, a substantially pure compound composition or a salt thereof is provided wherein the composition does or does not contain more than 3% impurity. In yet another variation, a substantially pure compound composition or a salt thereof is provided wherein the composition does or does not contain more than 1% impurity. In a further variation, a substantially pure compound composition or a salt thereof is provided, wherein the composition does or does not contain more than 0.5% impurity. In still other variations, a substantially pure compound composition means that the composition contains no more than 10% or preferably no more than 5% or more preferably no more than 3% or even more preferably no more than 1% of impurity or more preferably not more than 0.5% impurity, which impurity may be the compound in a different stereochemical form. For example, a substantially pure compound (S) composition means that the composition contains no more than 10% or no more than 5% or no more than 3% or no more than 1% or no more than 0 .5% of the (R) form of the compound.

[0483] In other embodiments, the purified forms and substantially pure forms of the compounds apply to any compounds of formulas (I), (IIa), (IIb), (IIIa), (IIIb), (IVa), (IVb ), (Va), (Va- 1), (Va-2), (Vb), (Vb-1), (Vb-2), (II-A-1), (II-A-2), (II-A-2i), (II-A-2ii), (II-A- 1a-1), (II-A-1a-2), (II-A-1a-3), (II-A -1b-1), (II-A-1b-2), (II-A-1c-1), (II-A-1c- 2), (II-A-1d-1), (II-A -1d-2), (II-A-1d-3), (II-A-2a-1), (II-A-2a-2), (II-A-2a-3), (II-A -2a-4), (II-A-2b-1), (II-A-2b-2), (II-A-2c-1), (II-A-2c-2), (II-A -2c-3), (II-A-2c-4), (II-A-2d-1), (II-A-2d-2), (II-A-2d-3), (II-A -2d-4), (II-A-2d-5), (II-A- 2d-6), (II-A-2e-1), (II-A-2e-2), (II-A -2e-3), (II-A-2e-4), (II-A-2e-5), (II-A- 2e-6), (II-A-2e-7), (II-A -2e-8), (II-A-2f-1), (II-A-2f-2), (II-A-2f-3), (II-A-2f- 4), (II-A -2f-5), (II-A-2f-6), (II-A-2f-7), (II-A-2f-8), (II-A-2f-9), (II-A -2f-10), (II-B-1), (II-B-2), (II-B-3), (II-B-1a), (II-B-2a), (II-B -2b), (II-B-3a), or (II-B-3b), a compound of Table 1 or Table 2, or any of compounds 1 to 329

[0484] In one variation, the compounds herein are synthetic compounds prepared for administration to an individual, such as a human. In another variation, compositions are provided containing a compound in substantially pure form. In another variation, the invention encompasses pharmaceutical compositions comprising a compound detailed herein and a pharmaceutically acceptable carrier or excipient. In another variation, methods of administering a compound are provided. The purified forms, pharmaceutical compositions and methods of administration of the compounds are suitable for any compound or form detailed herein.

[0485] A compound detailed herein or salt thereof may be formulated for any available delivery route, including an oral, mucosal (e.g., nasal, sublingual, vaginal, buccal, or rectal), parenteral (e.g., example, intramuscular, subcutaneous or intravenous), topical or transdermal. A compound or salt thereof may be formulated with suitable carriers to provide delivery forms including, but not limited to, tablets, oval-shaped tablets, capsules (such as hard gelatin capsules or elastic soft gelatin capsules), capsules, troches lozenges, gums, dispersions, suppositories, ointments, poultices, pastes, powders, dressings, creams, solutions, patches, aerosols (e.g., nasal spray or inhalers), gels, suspensions (e.g., aqueous or non-aqueous liquid suspensions, oil-in-water emulsions or water-in-oil emulsions), solutions and elixirs.

[0486] One or more compounds described herein or a salt thereof can be used in the preparation of a formulation, such as a pharmaceutical formulation, by combining the compound or compounds, or a salt thereof, as an active ingredient with a carrier pharmaceutically acceptable, such as those mentioned above. Depending on the therapeutic form of the system (e.g., transdermal patch vs. oral tablet), the vehicle can take several forms. Furthermore, pharmaceutical formulations may contain preservatives, solubilizers, stabilizers, rewetting agents, emulsifiers, sweeteners, colorants, adjusters and salts for adjusting osmotic pressure, buffers, coating agents or antioxidants. Formulations comprising the compound may also contain other substances that have valuable therapeutic properties. Pharmaceutical formulations can be prepared by known pharmaceutical methods. Suitable formulations can be found, for example, in Remington: The Science and Practice of Pharmaci, Lippincott Williams & Wilkins, 21aed. (2005), which is incorporated into this document by reference.

[0487] The compounds described herein can be administered to individuals (e.g., a human being) in a form of generally accepted oral compositions, such as tablets, coated tablets and gel capsules in a hard or soft shell, emulsions or suspensions. Examples of vehicles, which can be used for the preparation of such compositions, are lactose, corn starch or its derivatives, talc, stearate or its salts, etc. Acceptable carriers for soft-shell gel capsules are, for example, vegetable oils, wax, fats, semi-solid and liquid polyols, and so on. Furthermore, pharmaceutical formulations may contain preservatives, solubilizers, stabilizers, rewetting agents, emulsifiers, sweeteners, colorants, adjusters and salts for adjusting osmotic pressure, buffers, coating agents or antioxidants.

[0488] Any of the compounds described herein can be formulated into a tablet in any dosage form described, for example, a compound as described herein or a pharmaceutically acceptable salt thereof can be formulated as a 10 mg tablet .

[0489] Compositions comprising a compound provided herein are also described. In one variation, the composition comprises a compound and a pharmaceutically acceptable carrier or excipient. In another variation, a substantially pure compound composition is provided. In some embodiments, the composition is for use as a human or veterinary medicine. In some embodiments, the composition is for use in a method described herein. In some embodiments, the composition is for use in treating a disease or disorder described herein.

METHODS OF USE

[0490] The compounds and compositions of the invention, such as a pharmaceutical composition containing a compound of any formula provided herein or a salt thereof and a pharmaceutically acceptable carrier or excipient, may be used in methods of administration and treatment as provided in this document. The compounds and compositions can also be used in in vitro methods, such as in vitro methods of administering a compound or composition to cells for screening purposes and/or for performing quality control assays.

[0491] In one aspect, there is provided a method of treating a fibrotic disease in an individual in need thereof which comprises administering to the individual a therapeutically effective amount of a compound of formula (I), or any variation thereof, e.g. , a compound of formula (I), (IIa), (IIb), (IIIa), (IIIb), (IVa), (IVb), (Va), (Va-1), (Va-2), ( Vb), (Vb-1) or (Vb-2), a compound selected from the compounds depicted in Table 1, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof. In one respect, the individual is a human being. The individual, such as a human, may need treatment, such as a human who has or is suspected of having a fibrotic disease. In one embodiment, a variation of the compounds includes any stereoisomer thereof.

[0492] In a further aspect, there is provided a method of treating a fibrotic disease in an individual in need, comprising administering to the individual a therapeutically effective amount of a compound of formulas (I), (IIa), (IIb) , (IIIa), (IIIb), (IVa), (IVb), (Va), (Va-1), (Va-2), (Vb), (Vb-1), (Vb-2), ( II-A-1), (II-A-2), (II-A-2i), (II-A-2ii), (II-A-1a-1), (II-A-1a-2) , (II-A-1a-3), (II-A- 1b-1), (II-A-1b-2), (II-A-1c-1), (II-A-1c-2) , (II-A-1d-1), (II-A-1d-2), (II-A-1d- 3), (II-A-2a-1), (II-A-2a-2) , (II-A-2a-3), (II-A-2a-4), (II-A-2b-1), (II-A-2b-2), (II-A-2c-1) , (II-A-2c-2), (II-A-2c-3), (II-A-2c-4), (II-A-2d-1), (II-A-2d-2) , (II-A-2d-3), (II-A-2d-4), (II-A-2d-5), (II-A-2d-6), (II-A-2e-1) , (II-A-2e-2), (II-A- 2e-3), (II-A-2e-4), (II-A-2e-5), (II-A-2e-6) , (II-A-2e-7), (II-A-2e-8), (II-A-2f- 1), (II-A-2f-2), (II-A-2f-3) , (II-A-2f-4), (II-A-2f-5), (II-A-2f-6), (II-A-2f-7), (II-A-2f-8) , (II-A-2f-9), (II-A-2f-10), (II-B-1), (II-B-2), (II-B-3), (II-B- 1a), (II-B-2a), (II-B-2b), (II-B-3a) or (II-B-3b), a compound selected from the compounds represented in Table 1 or Table 2, or any of compounds 1 to 329, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof. In one respect, the individual is a human being. The individual, such as a human, may need treatment, such as a human who has or is suspected of having a fibrotic disease. In one embodiment, a variation of the compounds includes any stereoisomer thereof.

[0493] In another aspect, a method is provided for delaying the onset and/or development of a fibrotic disease in an individual (such as a human being) who is at risk of developing a fibrotic disease. It is recognized that developmental delay may encompass prevention if the individual does not develop fibrotic disease. An individual at risk for developing a fibrotic disease in an aspect has or is suspected of having one or more risk factors for developing a fibrotic disease. Risk factors for fibrotic disease may include an individual's age (e.g., middle-aged or older adults), the presence of inflammation, having one or more genetic components associated with the development of a fibrotic disease, medical history, such as treatment with a drug or procedure believed to be associated with an increased susceptibility to fibrosis (e.g., radiology) or a medical condition believed to be associated with fibrosis, a history of smoking, the presence of occupational and/or environmental factors , such as exposure to pollutants associated with the development of a fibrotic disease. In some embodiments, the individual at risk for developing a fibrotic disease is an individual who has or is suspected of having NAFLD, NASH, CKD, scleroderma, Crohn's disease, NSIP, PSC, PBC, or is an individual who has had or is suspected of having of having had a myocardial infarction.

[0494] In some embodiments, fibrotic disease is fibrosis of a tissue, such as the lung (pulmonary fibrosis), liver, skin, heart (cardiac fibrosis), kidney (renal fibrosis), or gastrointestinal tract (fibrosis). gastrointestinal).

[0495] In some embodiments, the fibrotic disease is pulmonary fibrosis (such as IPF), hepatic fibrosis, cutaneous fibrosis, scleroderma, cardiac fibrosis, renal fibrosis, gastrointestinal fibrosis, primary sclerosing cholangitis, or biliary fibrosis (such as PBC).

[0496] In some embodiments, the fibrotic disease is a pulmonary fibrosis, e.g., idiopathic pulmonary fibrosis (IPF), interstitial lung disease, sclerosis-associated interstitial lung disease, or radiation-induced pulmonary fibrosis. In some embodiments, the individual at risk for developing a fibrotic disease is an individual who has or is suspected of having a history of viral lung infections.

[0497] In some embodiments, the fibrotic disease is primary sclerosing cholangitis or biliary fibrosis.

[0498] In some embodiments, the fibrotic disease is nonspecific fibrotic interstitial pneumonia (NSIP).

[0499] In some embodiments, the fibrotic disease is liver fibrosis, e.g., infectious liver fibrosis (from pathogens such as HCV, HBV, or parasites such as schistosomiasis), NASH, alcoholic liver disease-induced liver fibrosis, steatosis-induced liver fibrosis alcoholic, non-alcoholic fatty liver disease and cirrhosis.

[0500] In some embodiments, the fibrotic disease is fibrosis of the biliary tract.

[0501] In some embodiments, the fibrotic disease is renal fibrosis, e.g., diabetic kidney disease, diabetic nephrosclerosis, hypertensive nephrosclerosis, diabetic nephropathy, focal segmental glomerulosclerosis ("FSGS"), Alport syndrome, chronic kidney disease, and acute kidney injury of contrast-induced nephropathy.

[0502] In some embodiments, the fibrotic disease is systemic and local sclerosis or scleroderma, keloids and hypertrophic scars or postsurgical adhesions.

[0503] In some embodiments, the fibrotic disease is atherosclerosis or restenosis.

[0504] In some embodiments, the fibrotic disease is a gastrointestinal fibrosis, for example, Crohn's disease.

[0505] In some embodiments, the fibrotic disease is cardiac fibrosis, for example, fibrosis induced after myocardial infarction and hereditary cardiomyopathy.

[0506] In one aspect, there is provided a compound of formula (I), or any variation thereof, for example, a compound of formula (I), (IIa), (IIb), (IIIa), (IIIb), (IVa), (IVb), (Va), (Va-1), (Va-2), (Vb), (Vb-1), or (Vb-2), a compound selected from the compounds depicted in Table 1, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, for use in treating a fibrotic disease.

[0507] Also provided is the use of a compound of formula (I), or any variation thereof, for example, a compound of formula (II), a compound selected from the compounds in Table 1, or a stereoisomer thereof. , or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament for the treatment of a fibrotic disease.

[0508] In another aspect, there is provided a method of inhibiting αVβ6 integrin in a subject comprising administering a compound of formula (I), or any variation thereof, for example, a compound of formula (IIa), ( IIb), (IIIa), (IIIb), (IVa), (IVb), (Va), (Va- 1), (Va-2), (Vb), (Vb-1) or (Vb-2) , a stereoisomer thereof, or a compound selected from the compounds depicted in Table 1, or a pharmaceutically acceptable salt thereof.

[0509] Also provided is a method of inhibiting TGFβ activation in a subject comprising administering a compound of formula (I), or any variation thereof, for example, a compound of formula (IIa), (IIb) , (IIIa), (IIIb), (IVa), (IVb), (Va), (Va- 1), (Va-2), (Vb), (Vb-1) or (Vb-2), a stereoisomer thereof, or a compound selected from the compounds depicted in Table 1, or a pharmaceutically acceptable salt thereof.

[0510] Also provided is a method of inhibiting αVβ6 integrin in an individual in need thereof, which comprises administering a compound of formula (I), or any variation thereof, for example, a compound of formula (IIa). , (IIb), (IIIa), (IIIb), (IVa), (IVb), (Va), (Va-1), (Va-2), (Vb), (Vb-1) or (Vb- 2), a compound selected from the compounds depicted in Table 1, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof. In such a method, the compound is a selective inhibitor of the αvβ6 integrin. In another such method, the compound does not substantially inhibit integrin α4β1, αvβ8 and/or α2β3. In yet another such method, the compound inhibits αvβ6 integrin, but does not substantially inhibit α4β1 integrin. In yet another method, the compound inhibits αvβ6 integrin, but does not substantially inhibit αvβ8 integrin. In another method, the compound inhibits αvβ6 integrin, but does not substantially inhibit α2β3 integrin. In one embodiment, a method is provided for inhibiting integrin αVβ6 and one or more of integrin αVβ1, αVβ3, αVβ5, α2β1, α3β1, integrin α6β1, α7β1 and α11β1 in an individual in need thereof. In another embodiment, a method for inhibiting integrin αvβ6 and integrin αvβ1 is provided. In another embodiment, a method for inhibiting αvβ6 integrin, αvβ3 integrin and αvβ5 integrin is provided. In another embodiment, a method for inhibiting αvβ6 integrin and α2β1 integrin is provided. In another embodiment, a method for inhibiting αvβ6 integrin, α2β1 integrin and α3β1 integrin is provided. In another embodiment, a method for inhibiting integrin αvβ6 and integrin α6β1 is provided. In another embodiment, a method for inhibiting integrin αvβ6 and integrin α7β1 is provided. In another embodiment, a method for inhibiting integrin αvβ6 and integrin α11β1 is provided. In all of these embodiments, in one aspect, the method of inhibition is for an individual in need thereof, such as an individual who has or is suspected of having a fibrotic disease, and wherein the method comprises administering to the individual a compound of formula (I ), or any variation thereof, for example, a compound of formula (IIa), (IIb), (IIIa), (IIIb), (IVa), (IVb), (Va), (Va-1), ( Va-2), (Vb), (Vb-1) or (Vb-2), a compound selected from the compounds depicted in Table 1, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof.

[0511] Also provided is a method of modulating at least one integrin in an individual, the at least one integrin comprising an αV subunit, the method comprising administering a compound of formula (I), or any variation thereof, for example, a compound of formula (IIa), (IIb), (IIIa), (IIIb), (IVa), (IVb), (Va), (Va-1), (Va-2), (Vb), (Vb-1) or (Vb-2), a stereoisomer thereof, or a compound selected from the compounds depicted in Table 1, or a pharmaceutically acceptable salt thereof. In another aspect, modulation comprises inhibiting at least one integrin in the individual. In another aspect, the at least one integrin comprises at least one of the αVβ1 integrin and the αVβ6 integrin. In another aspect, the individual has or is at risk of having a fibrotic disease selected from the group consisting of: idiopathic pulmonary fibrosis (IPF), interstitial lung disease, radiation-induced pulmonary fibrosis, non-alcoholic fatty liver disease (NAFLD) , non-alcoholic steatohepatitis (NASH), alcoholic liver disease-induced fibrosis, Alport syndrome, primary sclerosing cholangitis (PSC), primary biliary cholangitis, biliary atresia, systemic sclerosis associated with interstitial lung disease, scleroderma, diabetic nephropathy, kidney disease diabetic, focal segmental glomerulosclerosis, chronic kidney disease and Crohn's disease; and the method comprises inhibiting one or both αVβ1 integrin and αVβ6 integrin in the subject, thereby treating the fibrotic disease in the subject. In another aspect, the individual is in need of treatment for NASH, wherein the effective amount administered to the individual is effective to inhibit at least αVβ1 integrin, thereby treating the individual for NASH. In another aspect, the individual is in need of treatment for IPF, wherein the effective amount administered to the individual is effective to inhibit at least αVβ6 integrin, thereby treating the individual for IPF. In another aspect, the individual is in need of treatment for PSC, and the effective amount administered to the individual is effective to inhibit at least one of integrin αVβ1 and integrin αVβ6, thereby treating the individual for PSC.

[0512] Also provided is a method for modulating the activation of TGFβ in a cell, comprising contacting the cell with the compound of formula (I), or any variation thereof, for example, a compound of formula (IIa), ( IIb), (IIIa), (IIIb), (IVa), (IVb), (Va), (Va- 1), (Va-2), (Vb), (Vb-1) or (Vb-2) , a stereoisomer thereof, or a compound selected from the compounds represented in Table 1, or a pharmaceutically acceptable salt thereof. In another aspect, the modulation comprises the inhibition of TGFβ activation in the cell. In another aspect, TGFβ activation is mediated in the cell by at least one of integrin αVβ1 and integrin αVβ6.

[0513] Also provided is a method of treating an individual in need thereof, comprising: administering to the individual a therapeutically effective amount of the compound of formula (I), or any variation thereof, for example, a compound of formula (IIa ), (IIb), (IIIa), (IIIb), (IVa), (IVb), (Va), (Va-1), (Va-2), (Vb), (Vb-1) or (Vb -2), a stereoisomer thereof, or a compound selected from the compounds represented in Table 1, or a pharmaceutically acceptable salt thereof, wherein the subject has at least one tissue in need of therapy and the tissue has at least one elevated level of: TGFβ activation and/or expression; αVβ1 integrin activity and/or expression; or αVβ6 integrin activity and/or expression; wherein the at least one elevated level is elevated compared to a healthy state of the tissue. In some aspects, the method selectively inhibits the αVβ1 integrin compared to the αVβ6 integrin in the individual. In some aspects, the method selectively inhibits the αVβ1 integrin compared to the αVβ6 integrin in the individual. In some aspects, the method inhibits both integrin αVβ1 and integrin αVβ6 in the individual. In some aspects, the method selectively inhibits both the αVβ1 integrin and the αVβ6 integrin compared to at least one other αV-containing integrin in the individual. In some aspects, the αVβ1 integrin is inhibited in one or more fibroblasts in the individual. In some aspects, the αVβ6 integrin is inhibited in one or more epithelial cells in the individual. In some aspects, the at least one tissue in the subject comprises one or more of: lung tissue, liver tissue, skin tissue, heart tissue, kidney tissue, gastrointestinal tissue, gallbladder tissue, and bile duct tissue.

[0514] In one aspect, there is provided a compound of formula (I), or any variation thereof, for example, a compound of formulas (IIa), (IIb), (IIIa), (IIIb), (IVa), (IVb), (Va), (Va-1), (Va-2), (Vb), (Vb-1), (Vb- 2), (II-A-1), (II-A-2 ), (II-A-2i), (II-A-2ii), (II-A-1a-1), (II-A-1a-2), (II-A-1a-3), (II -A-1b-1), (II-A-1b-2), (II-A-1c-1), (II-A-1c-2), (II-A-1d-1), (II -A-1d-2), (II- A-1d-3), (II-A-2a-1), (II-A-2a-2), (II-A-2a-3), (II -A-2a-4), (II-A-2b-1), (II-A- 2b-2), (II-A-2c-1), (II-A-2c-2), (II -A-2c-3), (II-A-2c-4), (II-A-2d-1), (II-A-2d- 2), (II-A-2d-3), (II -A-2d-4), (II-A-2d-5), (II-A-2d-6), (II-A-2e-1), (II-A-2e-2), (II -A-2e-3), (II-A-2e-4), (II-A-2e-5), (II-A-2e-6), (II-A-2e-7), (II -A-2e-8), (II-A-2f-1), (II-A-2f-2), (II-A-2f-3), (II-A-2f-4), (II -A-2f-5), (II-A-2f-6), (II-A-2f- 7), (II-A-2f-8), (II-A-2f-9), (II -A-2f-10), (II-B-1), (II-B-2), (II-B-3), (II-B-1a), (II-B-2a), (II -B-2b), (II-B-3a) or (II-B-3b), a compound selected from the compounds represented in Table 1 or Table 2, or any of compounds 1 to 329, or a stereoisomer of same, or a pharmaceutically acceptable salt thereof, for use in treating a fibrotic disease.

[0515] Also provided is the use of a compound of formulas (I), (IIa), (IIb), (IIIa), (IIIb), (IVa), (IVb), (Va), (Va-1) , (Va-2), (Vb), (Vb-1), (Vb- 2), (II-A-1), (II-A-2), (II-A-2i), (II- A-2ii), (II-A-1a-1), (II-A-1a-2), (II-A-1a-3), (II-A-1b-1), (II-A- 1b-2), (II-A-1c-1), (II-A-1c-2), (II-A-1d-1), (II-A-1d-2), (II-A- 1d-3), (II-A-2a-1), (II-A-2a-2), (II-A-2a-3), (II-A-2a-4), (II-A- 2b-1), (II-A- 2b-2), (II-A-2c-1), (II-A-2c-2), (II-A-2c-3), (II-A- 2c-4), (II-A-2d-1), (II-A-2d- 2), (II-A-2d-3), (II-A-2d-4), (II-A- 2d-5), (II-A-2d-6), (II-A-2e-1), (II-A-2e-2), (II-A-2e-3), (II-A- 2e-4), (II-A-2e-5), (II-A-2e-6), (II-A-2e-7), (II-A-2e-8), (II-A- 2f-1), (II-A-2f-2), (II-A-2f-3), (II-A-2f-4), (II-A-2f-5), (II-A- 2f-6), (II-A-2f- 7), (II-A-2f-8), (II-A-2f-9), (II-A-2f-10), (II-B- 1), (II-B-2), (II-B-3), (II-B-1a), (II-B-2a), (II-B-2b), (II-B-3a) or (II-B-3b), a compound selected from the compounds represented in Table 1 or Table 2, or any of compounds 1 to 329, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, in the manufacture of a medicine for the treatment of a fibrotic disease.

[0516] In another aspect, there is provided a method of inhibiting αvβ6 integrin in an individual comprising administering a compound of formulas (I), (IIa), (IIb), (IIIa), (IIIb), (IVa ), (IVb), (Va), (Va- 1), (Va-2), (Vb), (Vb-1), (Vb-2), (II-A-1), (II-A -2), (II-A-2i), (II-A-2ii), (II-A- 1a-1), (II-A-1a-2), (II-A-1a-3), (II-A-1b-1), (II-A-1b-2), (II-A-1c-1), (II-A-1c- 2), (II-A-1d-1), (II-A-1d-2), (II-A-1d-3), (II-A-2a-1), (II-A-2a-2), (II-A-2a-3), (II-A-2a-4), (II-A-2b-1), (II-A-2b-2), (II-A-2c-1), (II-A-2c-2), (II-A-2c-3), (II-A-2c-4), (II-A-2d-1), (II-A-2d-2), (II-A-2d-3), (II-A-2d-4), (II-A-2d-5), (II-A- 2d-6), (II-A-2e-1), (II-A-2e-2), (II-A-2e-3), (II-A-2e-4), (II-A-2e-5), (II-A- 2e-6), (II-A-2e-7), (II-A-2e-8), (II-A-2f-1), (II-A-2f-2), (II-A-2f-3), (II-A-2f- 4), (II-A-2f-5), (II-A-2f-6), (II-A-2f-7), (II-A-2f-8), (II-A-2f-9), (II-A-2f-10), (II-B-1), (II-B-2), (II-B-3), (II-B-1a), (II-B-2a), (II-B-2b), (II-B-3a), or (II-B-3b), a compound selected from the compounds represented in Table 1 or Table 2, or any of compounds 1 to 329, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof.

[0517] Also provided is a method for inhibiting the activation of TGFβ in a cell comprising administering to the cell a compound of formulas (I), (IIa), (IIb), (IIIa), (IIIb), (IVa ), (IVb), (Va), (Va- 1), (Va-2), (Vb), (Vb-1), (Vb-2), (II-A-1), (II-A -2), (II-A-2i), (II-A-2ii), (II-A- 1a-1), (II-A-1a-2), (II-A-1a-3), (II-A-1b-1), (II-A-1b-2), (II-A-1c-1), (II-A-1c- 2), (II-A-1d-1), (II-A-1d-2), (II-A-1d-3), (II-A-2a-1), (II-A-2a-2), (II-A-2a-3), (II-A-2a-4), (II-A-2b-1), (II-A-2b-2), (II-A-2c-1), (II-A-2c-2), (II-A-2c-3), (II-A-2c-4), (II-A-2d-1), (II-A-2d-2), (II-A-2d-3), (II-A-2d-4), (II-A-2d-5), (II-A- 2d-6), (II-A-2e-1), (II-A-2e-2), (II-A-2e-3), (II-A-2e-4), (II-A-2e-5), (II-A- 2e-6), (II-A-2e-7), (II-A-2e-8), (II-A-2f-1), (II-A-2f-2), (II-A-2f-3), (II-A-2f- 4), (II-A-2f-5), (II-A-2f-6), (II-A-2f-7), (II-A-2f-8), (II-A-2f-9), (II-A-2f-10), (II-B-1), (II-B-2), (II-B-3), (II-B-1a), (II-B-2a), (II-B-2b), (II-B-3a) or (II-B-3b), a compound selected from the compounds represented in Table 1 or Table 2, or any of compounds 1 to 329, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof.

[0518] Also provided is a method of inhibiting αvβ6 integrin in an individual in need, comprising administering to the individual a compound of formulas (I), (IIa), (IIb), (IIIa), (IIIb), ( IVa), (IVb), (Va), (Va-1), (Va-2), (Vb), (Vb-1), (Vb-2), (II-A- 1), (II- A-2), (II-A-2i), (II-A-2ii), (II-A-1a-1), (II-A-1a-2), (II-A-1a-3) , (II-A- 1b-1), (II-A-1b-2), (II-A-1c-1), (II-A-1c-2), (II-A-1d-1) , (II-A-1d-2), (II-A-1d- 3), (II-A-2a-1), (II-A-2a-2), (II-A-2a-3) , (II-A-2a-4), (II-A-2b-1), (II-A-2b-2), (II-A-2c-1), (II-A-2c-2) , (II-A-2c-3), (II-A-2c-4), (II-A-2d-1), (II-A-2d-2), (II-A-2d-3) , (II-A-2d-4), (II-A-2d-5), (II-A-2d-6), (II-A-2e-1), (II-A-2e-2) , (II-A- 2e-3), (II-A-2e-4), (II-A-2e-5), (II-A-2e-6), (II-A-2e-7) , (II-A-2e-8), (II-A-2f- 1), (II-A-2f-2), (II-A-2f-3), (II-A-2f-4) , (II-A-2f-5), (II-A-2f-6), (II-A-2f-7), (II-A-2f-8), (II-A-2f-9) , (II-A-2f-10), (II-B-1), (II-B-2), (II-B-3), (II-B-1a), (II-B- 2a) , (II-B-2b), (II-B-3a) or (II-B-3b), a compound selected from the compounds represented in Table 1 or Table 2, or any of compounds 1 to 329, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof. In such a method, the compound is a selective inhibitor of the αvβ6 integrin. In another such method, the compound does not substantially inhibit integrin α4β1, αvβ8 and/or α2β3. In yet another such method, the compound inhibits αvβ6 integrin, but does not substantially inhibit α4β1 integrin. In yet another method, the compound inhibits αvβ6 integrin, but does not substantially inhibit αvβ8 integrin. In another method, the compound inhibits αvβ6 integrin, but does not substantially inhibit α2β3 integrin. In one embodiment, a method is provided for inhibiting integrin αVβ6 and one or more of integrin αVβ1, αVβ3, αVβ5, α2β1, α3β1, integrin α6β1, α7β1 and α11β1 in an individual in need thereof. In another embodiment, a method for inhibiting integrin αvβ6 and integrin αvβ1 is provided. In another embodiment, a method for inhibiting αvβ6 integrin, αvβ3 integrin and αvβ5 integrin is provided. In another embodiment, a method for inhibiting αvβ6 integrin and α2β1 integrin is provided. In another embodiment, a method for inhibiting αvβ6 integrin, α2β1 integrin and α3β1 integrin is provided. In another embodiment, a method for inhibiting integrin αvβ6 and integrin α6β1 is provided. In another embodiment, a method for inhibiting integrin αvβ6 and integrin α7β1 is provided. In another embodiment, a method for inhibiting integrin αvβ6 and integrin α11β1 is provided. In all of these embodiments, in one aspect, the method of inhibition is for an individual in need thereof, such as an individual who has or is suspected of having a fibrotic disease, and wherein the method comprises administering to the individual a compound of formulas (I), (IIa), (IIb), (IIIa), (IIIb), (IVa), (IVb), (Va), (Va-1), (Va-2), (Vb), (Vb-1), (Vb-2), (II-A- 1), (II-A-2), (II-A-2i), (II-A-2ii), (II-A-1a -1), (II-A-1a-2), (II-A-1a-3), (II-A- 1b-1), (II-A-1b-2), (II-A-1c -1), (II-A-1c-2), (II-A-1d-1), (II-A-1d-2), (II-A-1d- 3), (II-A-2a -1), (II-A-2a-2), (II-A-2a-3), (II-A-2a-4), (II-A-2b-1), (II-A-2b -2), (II-A-2c-1), (II-A-2c-2), (II-A-2c-3), (II-A-2c-4), (II-A-2d -1), (II-A-2d-2), (II-A-2d-3), (II-A-2d-4), (II-A-2d-5), (II-A-2d -6), (II-A-2e-1), (II-A-2e-2), (II-A- 2e-3), (II-A-2e-4), (II-A-2e -5), (II-A-2e-6), (II-A-2e-7), (II-A-2e-8), (II-A-2f- 1), (II-A-2f -2), (II-A-2f-3), (II-A-2f-4), (II-A-2f-5), (II-A-2f-6), (II-A-2f -7), (II-A-2f-8), (II-A-2f-9), (II-A-2f-10), (II-B-1), (II-B-2), (II-B-3), (II-B-1a), (II-B-2a), (II-B-2b), (II-B-3a) or (II-B-3b), a compound selected from compounds represented in Table 1 or Table 2, or any of compounds 1 to 329, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof.

[0519] Also provided is a method of modulating at least one integrin in an individual, the at least one integrin comprising an αV subunit, the method comprising administering to the individual an effective amount of the compound of formulas (I ), (IIa), (IIb), (IIIa), (IIIb), (IVa), (IVb), (Va), (Va- 1), (Va-2), (Vb), (Vb-1 ), (Vb-2), (II-A-1), (II-A-2), (II-A-2i), (II-A-2ii), (II-A- 1a-1), (II-A-1a-2), (II-A-1a-3), (II-A-1b-1), (II-A-1b-2), (II-A-1c-1), (II-A-1c- 2), (II-A-1d-1), (II-A-1d-2), (II-A-1d-3), (II-A-2a-1), (II-A-2a-2), (II-A-2a-3), (II-A-2a-4), (II-A-2b-1), (II-A-2b-2), (II-A-2c-1), (II-A-2c-2), (II-A-2c-3), (II-A-2c-4), (II-A-2d-1), (II-A-2d-2), (II-A-2d-3), (II-A-2d-4), (II-A-2d-5), (II-A- 2d-6), (II-A-2e-1), (II-A-2e-2), (II-A-2e-3), (II-A-2e-4), (II-A-2e-5), (II-A- 2e-6), (II-A-2e-7), (II-A-2e-8), (II-A-2f-1), (II-A-2f-2), (II-A-2f-3), (II-A-2f- 4), (II-A-2f-5), (II-A-2f-6), (II-A-2f-7), (II-A-2f-8), (II-A-2f-9), (II-A-2f-10), (II-B-1), (II-B-2), (II-B -3), (II-B-1a), (II-B-2a), (II-B-2b), (II-B-3a) or (II-B-3b), a compound selected from the compounds represented in Table 1 or Table 2, or any of compounds 1 to 329, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof. In another aspect, modulation comprises inhibiting at least one integrin in the individual. In another aspect, the at least one integrin comprises at least one of the αVβ1 integrin and the αVβ6 integrin. In another aspect, the individual has or is at risk of having a fibrotic disease selected from the group consisting of: idiopathic pulmonary fibrosis (IPF), interstitial lung disease, radiation-induced pulmonary fibrosis, non-alcoholic fatty liver disease (NAFLD) , non-alcoholic steatohepatitis (NASH), alcoholic liver disease-induced fibrosis, Alport syndrome, primary sclerosing cholangitis (PSC), primary biliary cholangitis, biliary atresia, systemic sclerosis associated with interstitial lung disease, scleroderma, diabetic nephropathy, kidney disease diabetic, focal segmental glomerulosclerosis, chronic kidney disease and Crohn's disease; and the method comprises inhibiting one or both αVβ1 integrin and αVβ6 integrin in the subject, thereby treating the fibrotic disease in the subject. In another aspect, the individual is in need of treatment for NASH, wherein the effective amount administered to the individual is effective to inhibit at least αVβ1 integrin, thereby treating the individual for NASH. In another aspect, the individual is in need of treatment for IPF, wherein the effective amount administered to the individual is effective to inhibit at least αVβ6 integrin, thereby treating the individual for IPF. In another aspect, the individual is in need of treatment for PSC, and the effective amount administered to the individual is effective to inhibit at least one of integrin αVβ1 and integrin αVβ6, thereby treating the individual for PSC.

[0520] Also provided is a method for modulating the activation of TGFβ in a cell, comprising contacting the cell with the compound of formulas (I), (IIa), (IIb), (IIIa), (IIIb), (IVa ), (IVb), (Va), (Va- 1), (Va-2), (Vb), (Vb-1), (Vb-2), (II-A-1), (II-A -2), (II-A-2i), (II-A-2ii), (II-A- 1a-1), (II-A-1a-2), (II-A-1a-3), (II-A-1b-1), (II-A-1b-2), (II-A-1c-1), (II-A-1c- 2), (II-A-1d-1), (II-A-1d-2), (II-A-1d-3), (II-A-2a-1), (II-A-2a-2), (II-A-2a-3), (II-A-2a-4), (II-A-2b-1), (II-A-2b-2), (II-A-2c-1), (II-A-2c-2), (II-A-2c-3), (II-A-2c-4), (II-A-2d-1), (II-A-2d-2), (II-A-2d-3), (II-A-2d-4), (II-A-2d-5), (II-A- 2d-6), (II-A-2e-1), (II-A-2e-2), (II-A-2e-3), (II-A-2e-4), (II-A-2e-5), (II-A- 2e-6), (II-A-2e-7), (II-A-2e-8), (II-A-2f-1), (II-A-2f-2), (II-A-2f-3), (II-A-2f- 4), (II-A-2f-5), (II-A-2f-6), (II-A-2f-7), (II-A-2f-8), (II-A-2f-9), (II-A-2f-10), (II-B-1), (II-B-2), (II-B-3), (II-B-1a), (II-B-2a), (II-B-2b), (II-B-3a) or (II-B-3b), a compound selected from the compounds represented in Table 1 or Table 2, or any of compounds 1 to 329, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof. In another aspect, the modulation comprises the inhibition of TGFβ activation in the cell. In another aspect, TGFβ activation is mediated in the cell by at least one of integrin αVβ1 and integrin αVβ6.

[0521] Also provided is a method of treating an individual in need, comprising: administering to the individual a therapeutically effective amount of the compound of formula (I), or any variation thereof, for example, a compound of formulas (I), (IIa), (IIb), (IIIa), (IIIb), (IVa), (IVb), (Va), (Va-1), (Va-2), (Vb), (Vb-1), (Vb-2), (II-A-1), (II-A-2), (II-A-2i), (II-A-2ii), (II-A-1a-1), (II -A-1a-2), (II-A- 1a-3), (II-A-1b-1), (II-A-1b-2), (II-A-1c-1), (II -A-1c-2), (II-A-1d-1), (II-A-1d- 2), (II-A-1d-3), (II-A-2a-1), (II -A-2a-2), (II-A-2a-3), (II-A-2a-4), (II-A-2b-1), (II-A-2b-2), (II -A-2c-1), (II-A-2c-2), (II-A-2c-3), (II-A-2c-4), (II-A-2d-1), (II - A-2d-2), (II-A-2d-3), (II-A-2d-4), (II-A-2d-5), (II-A-2d-6), (II -A-2e-1), (II-A- 2e-2), (II-A-2e-3), (II-A-2e-4), (II-A-2e-5), (II -A-2e-6), (II-A-2e-7), (II-A- 2e-8), (II-A-2f-1), (II-A-2f-2), (II -A-2f-3), (II-A-2f-4), (II-A-2f-5), (II-A-2f-6), (II-A-2f-7), (II -A-2f-8), (II-A-2f-9), (II-A-2f-10), (II-B-1), (II-B-2), (II-B-3 ), (II-B-1a), (II-B-2a), (II-B-2b), (II-B-3a) or (II-B-3b), a compound selected from the compounds represented in Table 1 or Table 2, or any of compounds 1 to 329, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, wherein the subject has at least one tissue in need of therapy and the tissue has at least one elevated level of: TGFβ activation and/or expression; αVβ1 integrin activity and/or expression; or αVβ6 integrin activity and/or expression; wherein the at least one elevated level is elevated compared to a healthy state of the tissue. In some aspects, the method selectively inhibits the αVβ1 integrin compared to the αVβ6 integrin in the individual. In some aspects, the method selectively inhibits the αVβ1 integrin compared to the αVβ6 integrin in the individual. In some aspects, the method inhibits both integrin αVβ1 and integrin αVβ6 in the individual. In some aspects, the method selectively inhibits both the αVβ1 integrin and the αVβ6 integrin compared to at least one other αV-containing integrin in the individual. In some aspects, the αVβ1 integrin is inhibited in one or more fibroblasts in the individual. In some aspects, the αVβ6 integrin is inhibited in one or more epithelial cells in the individual. In some aspects, the at least one tissue in the subject comprises one or more of: lung tissue, liver tissue, skin tissue, heart tissue, kidney tissue, gastrointestinal tissue, gallbladder tissue, and bile duct tissue.

[0522] In any of the described methods, in one aspect, the individual is a human being, such as a human being who needs the method. The individual may be a human being who has been diagnosed with or is suspected of having a fibrotic disease. The individual may be a human being with no detectable disease, but with one or more risk factors for developing a fibrotic disease.

KITS

[0523] The invention further provides kits for carrying out the methods of the invention, which comprise one or more compounds described in the present document, or a salt thereof, or a pharmacological composition comprising a compound described in the present document. Kits may use any of the compounds disclosed herein. In one variation, the kit uses a compound described herein or a pharmaceutically acceptable salt thereof. The kits may be used for any one or more of the uses described herein and, accordingly, may contain instructions for use in treating a fibrotic disease.

[0524] Kits generally include suitable packaging. Kits may comprise one or more containers comprising any compound described herein. Each component (if there is more than one component) may be packaged in separate containers or some components may be combined in one container where cross-reactivity and shelf life permit. One or more components of a kit may be sterile and/or may be contained in sterile packaging.

[0525] Kits may be in unit dosage forms, bulk packaging (e.g., multi-dose packaging) or subunit doses. For example, kits may be provided that contain sufficient dosages of a compound as disclosed herein (e.g., a therapeutically effective amount) and/or a second pharmaceutically active compound useful for a disease detailed herein (e.g., fibrosis). to provide effective treatment to an individual for an extended period, such as any one week, 2 weeks, 3 weeks, 4 weeks, 6 weeks, 8 weeks, 3 months, 4 months, 5 months, 7 months, 8 months, 9 months or more. Kits may also include multiple unit doses of the compounds and instructions for use and be packaged in quantities sufficient for storage and use in pharmacies (e.g., hospital pharmacies and compounding pharmacies).

[0526] Kits may optionally include a set of instructions, generally written instructions, although electronic storage media (e.g., magnetic floppy disk or optical disk) that contain instructions are also acceptable, relating to the use of component (or components) of the methods of the present invention. Instructions included in the kit generally include information about the components and administration of the same to an individual.

GENERAL PROCEDURES

[0527] The compounds provided herein can be prepared according to the General Schemes, as exemplified by the General Procedures and Examples.

[0528] When a specific stereoisomer, or an unspecified stereoisomer, or a mixture of stereoisomers is shown in the following general procedures, it is understood that similar chemical transformations can be carried out on other specific stereoisomers, or an unspecified stereoisomer, or mixtures thereof . For example, a hydrolysis reaction of an L-homoserinate ester to an L-homoserine (i.e., free acid) can also be carried out on a D-homoserinate ester to prepare a D-homoserine, or on a mixture of a L-homoserinate ester and a D-homoserinate ester to prepare a mixture of an L-homoserine and a D-homoserine. As another example, reactions of functional groups in a compound containing a trans-cyclobutyl group can also be carried out on a compound containing a cis-cyclobutyl group, or in a mixture of a compound containing a cis-cyclobutyl group and a compound containing a trans group-cyclobutyl group. As another example, functional group reactions in a compound containing a cycloalkyl group Y can also be carried out in a compound without a group Y (i.e., where the ligand is -L1-O-L2-L3- as defined in Formula (I)), or in a mixture of a compound containing a cycloalkyl group and a compound without a Y group.

[0529] Some of the following general procedures use specific compounds to illustrate a general reaction (e.g., deprotection of a compound that has a Boc-protected amine to a compound that has a deprotected amine using acid). The general reaction may be carried out on other specific compounds with the same functional group (e.g., a different compound with a protected amine in which the Boc protecting group can be removed using acid in the same manner), provided that such other specific compounds do not contain additional functional groups affected by the overall reaction (i.e., such other specific compounds do not contain acid-sensitive functional groups), or if the effect of the overall reaction on such additional functional groups is desired (e.g., such other specific compounds have another group which is affected by the acid, and the effect of the acid on this other group is a desirable reaction).

[0530] Where specific reagents or solvents are specified for reactions in general procedures, one skilled in the art will recognize that other reagents or solvents may be substituted as desired. For example, acetylation is carried out in the general examples with acetic anhydride, but an active ester of acetic acid can also be used. For example, when hydrochloric acid is used to remove a Boc group, trifluoroacetic acid can be used in its place. As another example, where HATU is used as a coupling reagent, BOP or PyBOP can be used instead. GENERAL PROCEDURE TO DETAILED PROCEDURES FOR GENERAL SCHEME A AND SCHEME D-1 v

[0531] (1r,3r)-3-((tert-butyldimethylsilyl)oxy)cyclobutane-1-methyl carboxylate. To a solution of (1r,3r)-3-hydroxycyclobutane-methyl 1-carboxylate (5.0 g, 38.42 mmol) in CH2Cl2 (100 ml) was added imidazole (3.92 g, 57.63 mmol) then TBSCl (6.95 g, 46.10 mmol) at room temperature and the resulting heterogeneous mixture was vigorously stirred for 30 minutes. The mixture was diluted with saturated NaHCO3 solution and water and stirred for 5 minutes. The layers were separated and the organic layer was washed with water (50 ml), dried over MgSO4 and concentrated in vacuo. The crude residue was purified by normal phase chromatography on silica gel to provide methyl (1r,3r)-3-((tert-butyldimethylsilyl)oxy)cyclobutane-1-carboxylate.

[0532] ((1r,3r)-3-((tert-butyldimethylsilyl)oxy)cyclobutyl)methanol. A solution of methyl (1r,3r)-3-((tert-butyldimethylsilyl)oxy)cyclobutane-1-carboxylate (9.19 g, 37.60 mmol) at -78 °C in THF (92 ml) was Dibal-H (1.0 M in heptane, 94 ml, 94.00 mmol) was added dropwise and the resulting solution was allowed to stir for 1 hour at -78°C. The mixture was then heated to 0°C and then to this was slowly added EtOAc (100 ml) followed by a saturated aqueous solution of sodium potassium tartrate (250 ml) and water (100 ml) and the resulting mixture was then left Warm to room temperature and stir vigorously for 4 hours. The layers were separated and the aqueous layer was extracted with EtOAc. The combined organic extracts were dried over MgSO4, filtered and concentrated in vacuo. The crude residue was purified by normal phase chromatography on silica gel to provide ((1r,3r)-3-((tert-butyldimethylsilyl)oxy)cyclobutyl)methanol.

[0533] tert-butyl((1r,3r)-3-(iodomethyl)cyclobutoxy)dimethylsilane. To a solution of PPh3 (13.09 g, 49.91 mmol) and imidazole (4.53 g, 66.54 mmol) in CH2Cl2 (78 ml) at 0 °C was slowly added I2 (12.24 g, 48 .24 mmol) and the mixture was stirred for a further 30 minutes and then allowed to warm to room temperature. A solution of ((1r,3r)-3-((tert-butyldimethylsilyl)oxy)cyclobutyl)methanol (7.2 g, 33.27 mmol) in CH2Cl2 (20 ml) was then added to the reaction mixture and stirred for 6 hours at room temperature. The reaction mixture was then diluted with NaHCO3 and stirred for 15 minutes. The layers were separated and the organic layer was washed with H2O, dried over MgSO4, filtered and concentrated in vacuo. The crude residue was purified by normal phase chromatography on silica gel to give tert-butyl((1r,3r)- 3-(iodomethyl)cyclobutoxy)dimethylsilane.

[0534] 4-((1r,3s)-3-hydroxycyclobutyl)butan-2-one. To a solution of acetone dimethylhydrazone (8.33 g, 83.13 mmol) at -78°C in THF (83 ml) was slowly added n-BuLi (at 2.5 M in hexanes, 32.59 ml, 81.46 mmol) causing a pale yellow suspension to occur. After completion of the addition, the resulting suspension was stirred for a further 15 minutes, at which time a solution of tert-butyl((1r,3r)-3-(iodomethyl)cyclobutoxy)dimethylsilane (10.85 g, 33.25 mmol) ) in THF (20 ml) was added slowly dropwise. The resulting mixture was heated to 0°C and stirred for 30 minutes and then carefully quenched with aqueous 1M HCl (250 ml) and acetone (50 ml). The resulting mixture was allowed to stir at room temperature overnight and then extracted with EtOAc. The combined organic extracts were dried over MgSO4, filtered and concentrated in vacuo. The crude residue was purified by normal phase column chromatography to provide 4-((1r,3s)-3-hydroxycyclobutyl)butan-2-one.

[0535] (1s,3r)-3-(2-(1,8-naphthyridin-2-yl)ethyl)cyclobutan-1-ol. A sealed tube containing 4-((1r,3s)-3-hydroxycyclobutyl)butan-2-one (2.46 g, 17.30 mmol) was charged with L-proline (996 mg, 8.65 mmol) and 2 -aminonicotinaldehyde (2.53 g, 20.76 mmol) and then diluted with 200 proof EtOH (50 ml) and then sealed and placed in an aluminum block and heated at 95 °C overnight. The reaction mixture was allowed to cool to room temperature and then concentrated in vacuo. The crude residue was purified by normal phase (1s,3r)-3-(2-(1,8-naphthyridin-2-yl)ethyl)cyclobutan-1-ol column chromatography.

[0536] 2-(2-((1r,3s)-3-(allyloxy)cyclobutyl)ethyl)-1,8-naphthyridine. To a solution of (1s,3r)-3-(2-(1,8-naphthyridin-2-yl)ethyl)cyclobutan-1-ol (3.36 g, 14.72 mmol) in THF/DMF at 2 :1 (34 ml) at room temperature was slowly added NaH (60% dispersion in mineral oil, 883 mg, 22.08 mmol) and the resulting mixture was stirred for 30 minutes, at which time allyl bromide (1.91 ml, 22.08 mmol) was added and the resulting mixture was heated at 50°C for 1 hour. The reaction mixture was cooled to room temperature and then carefully diluted with saturated NaHCO3 and H2O solution. The resulting mixture was extracted with 4:1 DCM/iPrOH and the combined organic extracts were dried over MgSO4, filtered and concentrated in vacuo. The crude residue was purified by normal phase column chromatography to provide 2-(2-((1r,3s)-3-(allyloxy)cyclobutyl)ethyl)-1,8-naphthyridine.

[0537] 2-((1s,3r)-3-(2-(1,8-naphthyridin-2-yl)ethyl)cyclobutoxy)acetaldehyde. To a solution of 2-(2-((1r,3s)-3-(allyloxy)cyclobutyl)ethyl)-1,8-naphthyridine (1.38 g, 5.14 mmol) in dioxane/H2O 3:1 (14 ml) was added 2,6-lutidine (1.2 ml, 10.28 mmol), NaIO4 (4.40 g, 20.56 mmol), then OsO4 (at 2.5 wt% in t-BuOH , 1.05 ml, 0.10 mmol) and the resulting mixture was allowed to stir at room temperature for 4 hours. The reaction mixture was diluted with saturated NaHCO3 and H2O and stirred for 15 minutes and then filtered through a coarse fritted funnel and the filter cake was rinsed with 4:1 DCM/iPrOH. The layers were separated and the aqueous layer was extracted with 4:1 DCM and the combined organic extracts were dried over MgSO4, filtered and concentrated in vacuo to give 2-((1s,3r)-3-(2-(1,8 -naphthyridin-2- yl)ethyl)cyclobutoxy)acetaldehyde.

[0538] Methyl 4-((1s,3r)-3-(2-(1,8-naphthyridin-2-yl)ethyl)cyclobutoxy)-2-((tert-butoxycarbonyl)amino)but-2-enoate . To a solution of 2-((1s,3r)-3-(2-(1,8-naphthyridin-2-yl)ethyl)cyclobutoxy)acetaldehyde in CH2Cl2 (14 ml) and to this was added 2-((tert methyl-ethyl-butoxycarbonyl)amino)-2-(dimethoxyphosphoryl)-acetate (2.29 g, 7.71 mmol), then DBU (1.16 ml, 7.71 mmol) and the resulting mixture was left to Stir at room temperature for 30 minutes and then concentrate in vacuo. The crude residue was purified by normal phase chromatography on silica gel to give 4-((1s,3r)-3-(2-(1,8-naphthyridin-2-yl)ethyl)cyclobutoxy)-2-(( methyl tert-butoxycarbonyl)amino)but-2-enoate.

[0539] N-(tert-butoxycarbonyl)-O-((1s,3r)-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl) cyclobutyl)methyl homoserinate. One vial containing methyl 4-((1s,3r)-3-(2-(1,8-naphthyridin-2-yl)ethyl)cyclobutoxy)-2-((tert-butoxycarbonyl)amino)but-2-enoate (2.27 g, 5.14 mmol) was charged with Pd(OH)2/C (20 wt% on carbon, 454 mg) and then diluted with MeOH (23 ml). The flask was then evacuated and filled with H2 for 3 cycles and then shaken under an H2 atmosphere for. The reaction mixture was filtered through a pad of Celite and then concentrated in vacuo. The crude residue was purified by normal phase column chromatography to provide N-(tert-butoxycarbonyl)-O-((1s,3r)-3-(2-(5,6,7,8-tetrahydro-1 ,8-naphthyridin-2-yl)ethyl)cyclobutyl)methyl homoserinate.

[0540] After synthesis of the racemic material as shown in the previous step, a chiral separation can be performed to produce two single enantiomers using chiral SFC with the following method: Chiralpak AY-H, 250 * 25 mm id 10 u; Mobile phase: A for CO2 and B for EtOH (0.1% NH3H2O); Gradient: B% = 45%; Flow rate: 80 g/min; Wavelength: 220 nm; Column temperature: 40 °C; System backpressure: 100 bar. GENERAL PROCEDURE B DETAILED PROCEDURES FOR THE GENERAL SCHEME BEO SCHEME E-1

[0541] (1s,3s)-3-((tert-butyldimethylsilyl)oxy)cyclobutane-1-methyl carboxylate. To a solution of (1s,3s)-3-hydroxycyclobutane-methyl 1-carboxylate (5.0 g, 38.16 mmol) in CH2Cl2 (100 ml) was added imidazole (3.92 g, 57.63 mmol) then TBSCl (6.95 g, 49.61 mmol) at room temperature and the resulting heterogeneous mixture was vigorously stirred for 30 minutes. The mixture was diluted with saturated NaHCO3 solution (50 ml) and water (50 ml) and stirred for 5 minutes. The layers were separated and the organic layer was washed with water (50 ml), dried over MgSO4 and concentrated in vacuo. The crude residue was purified by normal phase chromatography on silica gel to provide methyl (1s,3s)-3-((tert-butyldimethylsilyl)oxy)cyclobutane-1-carboxylate.

[0542] ((1s,3s)-3-((tert-butyldimethylsilyl)oxy)cyclobutyl)methanol. A solution of methyl (1s,3s)-3-((tert-butyldimethylsilyl)oxy)cyclobutane-1-carboxylate (9.20 g, 37.76 mmol) at -78 °C in THF (92 ml) was Dibal-H (1.0 M in heptane, 113 ml, 113.00 mmol) was added dropwise and the resulting solution was allowed to stir for 1 hour at -78°C. The mixture was then heated to 0°C and then to this was slowly added EtOAc (100 ml) followed by a saturated aqueous solution of sodium potassium tartrate (250 ml) and water (100 ml) and the resulting mixture was then left Warm to room temperature and stir vigorously for 4 hours. The layers were separated and the aqueous layer was extracted with EtOAc. The combined organic extracts were dried over MgSO4, filtered and concentrated in vacuo. The crude residue was purified by normal phase chromatography on silica gel to provide ((1s,3s)-3-((tert-butyldimethylsilyl)oxy)cyclobutyl)methanol. 1

[0543] Tert-butyl((1s,3s)-3-(iodomethyl)cyclobutoxy)dimethylsilane. To a solution of PPh3 (12.80 g, 48.79 mmol) and imidazole (4.43 g, 65.05 mmol) in CH2Cl2 (72 ml) at 0°C was slowly added I2 (11.97 g, 47 .16 mmol) and the mixture was stirred for a further 30 minutes and then allowed to warm to room temperature. A solution of ((1s,3s)- 3-((tert-butyldimethylsilyl)oxy)cyclobutyl)methanol (7.04 g, 32.53 mmol) in CH2Cl2 (20 ml) was then added to the reaction mixture and stirred for 6 hours at room temperature. The reaction mixture was then diluted with NaHCO3 and stirred for 15 minutes. The layers were separated and the organic layer was washed with H2O, dried over MgSO4, filtered and concentrated in vacuo. The crude residue was purified by normal phase chromatography on silica gel to give tert-butyl((1s,3s)- 3-(iodomethyl)cyclobutoxy)dimethylsilane.

[0544] 4-((1s,3r)-3-hydroxycyclobutyl)butan-2-one. To a solution of acetone dimethylhydrazone (8.15 g, 81.39 mmol) at -78°C in THF (82 ml) was slowly added n-BuLi (at 2.5 M in hexanes, 31.25 ml, 78.13 mmol) causing a pale yellow suspension. After completion of the addition, the resulting suspension was stirred for a further 15 minutes, at which time a solution of tert-butyl((1s,3s)-3-(iodomethyl)cyclobutoxy)dimethylsilane (10.62 g, 32.55 mmol) ) in THF (20 ml) was added slowly dropwise. The resulting mixture was heated to 0°C and stirred for 30 minutes and then carefully quenched with aqueous 1M HCl (250 ml) and acetone (50 ml). The resulting mixture was allowed to stir at room temperature overnight and then extracted with EtOAc. The combined organic extracts were dried over MgSO4, filtered and concentrated in vacuo. The crude residue was purified by normal phase column chromatography to provide 4-((1s,3r)-3-hydroxycyclobutyl)butan-2-one.

[0545] (1r,3s)-3-(2-(1,8-naphthyridin-2-yl)ethyl)cyclobutan-1-ol. A sealed tube containing 4-((1s,3r)-3-hydroxycyclobutyl)butan-2-one (2.72 g, 19.18 mmol) was charged with L-proline (1.10 g, 9.59 mmol) and 2-aminonicotinaldehyde (3.51 g, 28.77 mmol) and then diluted with 200 proof EtOH (50 ml) and then sealed and placed in an aluminum block and heated to 95 °C for at night. The reaction mixture was allowed to cool to room temperature and then concentrated in vacuo. The crude residue was purified by normal phase column chromatography to provide (1r,3s)-3-(2-(1,8-naphthyridin-2-yl)ethyl)cyclobutan-1-ol.

[0546] 2-(2-((1s,3r)-3-(allyloxy)cyclobutyl)ethyl)-1,8-naphthyridine. To a solution of (1r,3s)-3-(2-(1,8-naphthyridin-2-yl)ethyl)cyclobutan-1-ol (3.72 g, 16.30 mmol) in THF/DMF at 2 :1 (37 ml) at room temperature was slowly added NaH (60% dispersion in mineral oil, 847 mg, 21.18 mmol) and the resulting mixture was stirred for 30 minutes, at which time allyl bromide (1.83 ml, 21.18 mmol) was added and the mixture was heated at 50°C for 1 hour. The reaction mixture was cooled to room temperature and then carefully diluted with saturated NaHCO3 and H2O solution. The resulting mixture was extracted with 4:1 DCM/iPrOH and the combined organic extracts were dried over MgSO4, filtered and concentrated in vacuo. The crude residue was purified by normal phase column chromatography to provide 2-(2-((1s,3r)-3-(allyloxy)cyclobutyl)ethyl)-1,8-naphthyridine.

[0547] 2-((1r,3s)-3-(2-(1,8-naphthyridin-2-yl)ethyl)cyclobutoxy)acetaldehyde. To a solution of 2-(2-((1s,3r)-3-(allyloxy)cyclobutyl)ethyl)-1,8-naphthyridine (946 mg, 3.53 mmol) in dioxane/H2O at 3:1 (10 ml) 2,6-lutidine (0.82 ml, 7.05 mmol) was added, NaIO4 (3.02 g, 14.10 mmol), then OsO4 (at 2.5 wt% in t-BuOH, 0 .88 ml, 0.07 mmol) and the resulting mixture was allowed to stir at room temperature for 4 hours. The reaction mixture was diluted with saturated NaHCO3 and H2O and stirred for 15 minutes and then filtered through a coarse frit funnel and the filter cake was rinsed with 4:1 DCM/iPrOH. The layers were separated and the aqueous layer was extracted with 4:1 DCM/iPrOH and the combined organic extracts were dried over Na2SO4, filtered and concentrated in vacuo to give 2-((1r,3s)-3-(2-( 1,8-naphthyridin-2-yl)ethyl)cyclobutoxy)acetaldehyde.

[0548] Methyl 4-((1r,3s)-3-(2-(1,8-naphthyridin-2-yl)ethyl)cyclobutoxy)-2-((tert-butoxycarbonyl)amino)but-2-enoate . To a solution of 2-((1r,3s)-3-(2-(1,8-naphthyridin-2-yl)ethyl)cyclobutoxy)acetaldehyde (953 mg, 3.53 mmol) in CH2Cl2 (10 ml) and to this was added methyl 2-((tert-butoxycarbonyl)amino)-2-(dimethoxyphosphoryl)acetate (1.57 g, 5.29 mmol), then DBU (0.64 ml, 4.23 mmol) and the resulting mixture was allowed to stir at room temperature for 30 minutes and then concentrated in vacuo. The crude residue was purified by normal phase column chromatography to provide 4-((1r,3s)-3-(2-(1,8-naphthyridin-2-yl)ethyl)cyclobutoxy)-2-((tert methyl-butoxycarbonyl)amino)but-2-enoate.

[0549] N-(tert-butoxycarbonyl)-O-((1r,3s)-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl) cyclobutyl)methyl homoserinate. A vial containing 4-((1r,3s)-3-(2-(1,8-naphthyridin-2-yl)ethyl)cyclobutoxy)-2-((tert-butoxycarbonyl)amino)but-2-enoate methyl (846 mg, 1.92 mmol) was loaded with Pd(OH)2 (at 20 wt% on carbon, 169 mg) and then diluted with MeOH (9 ml). The flask was then evacuated and filled with H2 for 3 cycles and then shaken under an H2 atmosphere for. The reaction mixture was filtered through a pad of Celite and then concentrated in vacuo. The crude residue was purified by normal phase column chromatography to provide N-(tert-butoxycarbonyl)-O-((1r,3s)-3-(2-(5,6,7,8-tetrahydro- 1,8-naphthyridin-2-yl)ethyl)cyclobutyl)methyl homoserinate.

[0550] After synthesis of the racemic material as shown in the previous step, a chiral separation can be performed to produce two single enantiomers using chiral SFC with the following method: Chiralpak AY-H 250 * 30 mm id 5 u; mobile phase: A for CO2 and B for EtOH (0.1% NH3H2O); gradient: B% = 50%; flow rate: 80 g/min; wavelength: 220 nm; column temperature: 40 °C; system backpressure: 100 bar. GENERAL PROCEDURE C DETAILED PROCEDURES FOR GENERAL SCHEME CEO F-1 SCHEME

[0551] 4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butan-1-ol. To a suspension of 4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butanoic acid hydrochloride (1.23 g, 4.79 mmol, 1.0 equiv) in THF was added to LiAlH4 (at 1.0 M in THF, 10.6 ml, 10.6 mmol) dropwise and the resulting mixture was refluxed overnight. The mixture was then cooled in an ice bath and to this was slowly added H2O (400 ml), then 1.0 M aqueous NaOH (400 ml), then H2O (400 ml) once more and stirred. stirred for 15 minutes and then a large excess of MgSO4 was added and stirred for an additional 30 minutes. The resulting organic mixture was filtered and then concentrated in vacuo to provide 4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butan-1-ol.

[0552] 7-(4-(allyloxy)butyl)-1,2,3,4-tetrahydro-1,8-naphthyridine. To a stirring suspension of NaH (60 wt% dispersion in mineral oil, 238 mg, 5.96 mmol) in THF (8.2 ml) at 0°C was added a solution of 4-(5.6, 7,8-tetrahydro-1,8-naphthyridin-2-yl)butan-1-ol (820 mg, 3.98 mmol) in THF (4.1 ml) dropwise. After completion of the addition, the ice bath was removed and the resulting mixture was stirred at room temperature for 30 minutes, at which time allyl bromide (400 μl, 4.62 mmol) was added dropwise. The suspension was stirred for an additional 6 hours at room temperature and then carefully diluted with H2O and EtOAc. The layers were separated and the aqueous layer was extracted with EtOAc. The combined organic extracts were dried over MgSO4, filtered and concentrated in vacuo. The crude residue was purified by silica gel chromatography to provide 7-(4-(allyloxy)butyl)-1,2,3,4-tetrahydro-1,8-naphthyridine.

[0553] 2-(4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butoxy)acetaldehyde. To a solution of 7-(4-(allyloxy)butyl)-1,2,3,4-tetrahydro-1,8-naphthyridine (582 mg, 2.36 mmol) in THF/H2O at 3:1 ( 6 ml) at room temperature NaIO4 (2.02 g, 9.44 mmol) was added followed by OsO4 (at 2.5 wt% in t-BuOH, 480 μl, 0.05 mmol). The resulting suspension was stirred at room temperature for 5 hours and then diluted with 1:1 saturated aqueous NaHCO3/saturated aqueous Na2S2O3 and EtOAc solution and then stirred for 1 hour at room temperature. The two-phase mixture was filtered through a small pad of Celite and the layers were separated. The aqueous layer was extracted with EtOAc and the combined organic extracts were dried over MgSO4, filtered and concentrated in vacuo to provide 2-(4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2- il)butoxy)acetaldehyde which was used without further purification.

[0554] 2-((tert-butoxycarbonyl)amino)-4-(4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butoxy)but-2-enoate methyl. To a solution of 2-(4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butoxy)acetaldehyde (586 mg, 2.36 mmol) in CH2Cl2 (6 ml) At room temperature, methyl 2-(((benzyloxy)carbonyl)amino)-2-(dimethoxyphosphoryl)acetate (860 mg, 2.60 mmol) was added followed by DBU (391 μl, 2.60 mmol) and stirred for 30 minutes at room temperature. The mixture was diluted with aqueous NH4Cl solution and stirred for 5 minutes at room temperature. The layers were separated and the aqueous layer was extracted with EtOAc. The combined organic extracts were dried over MgSO4, filtered and concentrated in vacuo. The crude residue was purified by silica gel chromatography to provide 2-((tert-butoxycarbonyl)amino)-4-(4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2- methyl yl)butoxy)but-2-enoate.

[0555] N-(tert-butoxycarbonyl)-O-(4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl)methyl homoserinate. One vial containing 2-((tert-butoxycarbonyl)amino)-4-(4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butoxy)but-2-enoate methyl (497 mg, 1.10 mmol) and 20 wt% Pd(OH)2 on carbon (100 mg) was diluted with MeOH (5 ml) and then evacuated and filled with H2 for 3 cycles and then , stirred under an H2 atmosphere for 3 hours. The resulting mixture was filtered through a pad of Celite and then concentrated in vacuo to give N-(tert-butoxycarbonyl)-O-(4-(5,6,7,8-tetrahydro-1,8 -naphthyridin-2- yl)butyl)methyl homoserinate (352 mg) which was used without further purification.

[0556] After synthesis of the racemic material as shown in the previous step, a chiral separation can be performed to produce two single enantiomers using chiral SFC with the following method: Chiralpak AY-H 250 * 30 mm id 5 u; mobile phase: A for CO2 and B for IPA (0.1% NH3H2O); gradient: B% = 40%; flow rate: 70 g/min; wavelength: 220 nm; column temperature: 40 °C; System backpressure: 100 bar. GENERAL PROCEDURE D

[0557] O-(cis-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)methyl homoserinate. To a solution of N-(tert-butoxycarbonyl)-O-(cis-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserinate of methyl (2.26 g, 5.05 mmol) in DCM (13 ml) was added 4N HCl in 1,4-dioxane (10 ml, 40 mmol). The reaction was allowed to stir at room temperature overnight. LCMS then showed the consumption of the starting material. The reaction was concentrated and used in the next step without further purification. GENERAL PROCEDURE AND

[0558] N-(quinazolin-4-yl)-O-(trans-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl) methyl homoserinate. To a solution of methyl O-(trans-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserinate (14 mg, 0.040 mmol ) in IPA (2 ml) 4-chloroquinazoline (9.9 mg, 0.060 mmol) and DIPEA (0.035 ml, 0.20 mmol) were added. The reaction was heated at 60°C for 18 hours. The reaction mixture was then concentrated and used directly in the next step.

[0559] General Procedure E can be used in the step of coupling compound 14A, or similar compounds, with compound 15A in General Scheme A, in General Scheme B, in General Scheme C, in General Scheme D-2, in Scheme General E-2, General Schedule F-2, General Schedule G-2, or General Schedule H. GENERAL PROCEDURE F

[0560] N-(isopropoxycarbonyl)-O-(trans-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)methyl homoserinate. Methyl O-(trans-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserinate (54 mg, 0.16 mmol) in CH2Cl2 (2.0 ml) DIPEA (60 mg, 0.47 mmol) was added, isopropyl carbon hydrochloride (23 mg, 0.19 mmol) was added and the resulting mixture was stirred at room temperature overnight and then concentrated in vacuum. The crude residue was used without further purification.

[0561] General Procedure F can be used in the step of coupling compound 14A, or similar compounds, with compound 16A in General Scheme A, in General Scheme B, in General Scheme C, in General Scheme D-2, in Scheme General E-2, General Schedule F-2, General Schedule G-2, or General Schedule H. GENERAL PROCEDURE G

[0562] N-(tert-butylcarbamoyl)-O-(trans-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserinate methyl. To a solution of methyl O-(trans-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserinate (71 mg, 0. 20 mmol) in DCM (2.4 ml) imidazole (15 mg, 0.22 mmol) and CDI (36 mg, 0.22 mmol) were added. This mixture was allowed to stir at room temperature for 30 min before adding tert-butylamine (22 mg, 0.31 mmol). The reaction was stirred at room temperature for 18 hours. LCMS indicated that methyl O-(trans-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserinate remained, and imidazole (15 mg , 0.22 mmol), CDI (36 mg, 0.22 mmol) and tert-butylamine (22 mg, 0.31 mmol) were added. After 5 hours, the reaction was concentrated in vacuo and the resulting crude residue was purified by normal-phase chromatography on silica gel to provide N-(tert-butylcarbamoyl)-O-(trans-3-(2-(5,6 ,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)methyl homoserinate. GENERAL PROCEDURE H

[0563] N-(diethylcarbamoyl)-O-(trans-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)methyl homoserinate. To a mixture of methyl O-(trans-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserinate (57 mg, 0. 16 mmol) in DCM (2.4 ml) at room temperature was added DIPEA (0.23 ml, 1.3 mmol), then diethylcarbamoyl chloride (0.10 ml, 0.82 mmol) and the mixture of resulting reaction was stirred at room temperature overnight. The mixture was concentrated in vacuo and the resulting crude residue was purified by reverse phase preparative HPLC to provide N-(diethylcarbamoyl)-O-(trans-3-(2-(5,6,7,8-tetrahydro -1,8- naphthyridin-2-yl)ethyl)cyclobutyl)methyl homoserinate.

[0564] General Procedure H can be used in the step of coupling compound 14A, or similar compounds, with compound 16A in General Scheme A, in General Scheme B, in General Scheme C, in General Scheme D-2, in Scheme General E-2, General Scheme F-2, General Scheme G-2 or General Scheme H. GENERAL PROCEDURE I

[0565] O-(cis-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)-N-(4-(trifluoromethyl)tetra -hydro-2H- pyran -4-carbonyl)methyl homoserinate. To a solution of methyl O-(cis-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserinate (1.62 g, 4.68 mmol) in DMF (10 ml) was added DIPEA (5.7 ml, 32 mmol), HATU (2.0 g, 5.1 mmol) and 4-(trifluoromethyl)tetrahydro-2H-pyran acid -4- carboxylic acid (1.0 g, 5.1 mmol). The reaction was allowed to stir at room temperature for 18 hours. LCMS showed mass of product, and the reaction was concentrated, diluted with EtOAc and saturated aqueous sodium bicarbonate solution. The layers were separated, and the aqueous layer was extracted twice. The combined organic layers were dried over sodium sulfate, filtered and concentrated to give the crude product, which was purified by silica gel chromatography to give O-(cis-3-(2-(5,6,7, Methyl 8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)-N-(4-(trifluoromethyl)tetrahydro-2H-pyran-4-carbonyl)homoserinate.

[0566] General Procedure I can be used in the step of coupling compound 14A, or similar compounds, with compound 16A in General Scheme A, in General Scheme B, in General Scheme C, in General Scheme D-2, in Scheme General E-2, General Schedule F-2, General Schedule G-2, or General Schedule H. GENERAL PROCEDURE J

[0567] The following transformation:

[0568] wherein R is R2f as defined for formula (I), or any applicable variations detailed herein, may be performed as exemplified below.

[0569] tert-butyl 3-((((2,5-dioxopyrrolidin-1-yl)oxy)carbonyl)oxy)-3-methylazetidine-1-carboxylate. To a mixture of tert-butyl 3-hydroxy-3-methylazetidine-1-carboxylate (1.1 g, 5.8 mmol) and N,N-diisopropylethylamine (2.02 ml, 11.6 mmol) in acetonitrile (10 ml) was added disuccinimidyl carbonate (3.0 g, 11.6 mmol) and the resulting mixture was stirred at room temperature for 14 hours. The reaction mixture was concentrated, diluted with water and extracted with EtAc. The combined organic layers were dried over sodium sulfate, filtered and concentrated in vacuo. The crude residue was purified by normal phase chromatography on silica gel to provide tert-butyl 3-((((2,5-dioxopyrrolidin-1-yl)oxy)carbonyl)oxy)-3-methylazetidine-1-carboxylate .

[0570] General Procedure J can be used to produce the appropriate reagent for use in General Procedure K GENERAL PROCEDURE K

[0571] The following transformation:

[0572] wherein R2fa as defined for formula (I), or any applicable variations detailed herein, may be performed as exemplified below.

[0573] 3-(((1-methoxy-1-oxo-4-(trans-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl tert-butyl)cyclobutoxy)butan-2-yl)carbamoyl)oxy)-3-methylazetidine-1-carboxylate. To a solution of methyl O-(trans-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserinate dihydrochloride (220.0 mg, 0.63 mmol) and N,N-diisopropylethylamine (0.4 ml, 2.5 mmol) in dichloromethane (2.0 ml) was added 3-(((((2,5-dioxopyrrolidin-1 tert-butyl-yl)oxy)carbonyl)oxy)-3-methylazetidine-1-carboxylate (249.5 mg, 0.8 mmol) and the resulting mixture was stirred at room temperature for 1 hour. concentrated in vacuo and purified by normal phase chromatography on silica gel to give 3-(((1-methoxy-1-oxo-4-(trans-3-(2-(5,6,7,8-tetra- tert-butyl hydro-1,8-naphthyridin-2-yl)ethyl)cyclobutoxy)butan-2-yl)carbamoyl)oxy)-3-methylazetidine-1-carboxylate.

[0574] General Procedure K can be used in the step of coupling compound 14A, or similar compounds, with compound 16A in General Scheme A, in General Scheme B, in General Scheme C, in General Scheme D-2, in Scheme General E-2, General Schedule F-2, General Schedule G-2, or General Schedule H. GENERAL PROCEDURE L

[0575] The following transformation:

[0576] where Z refers to that portion of the molecule that connects the -(O)nC(O)N(H)CH(COOCH3)L1- portion of the molecule with the remainder of the chemical portion R2, where n is 0 or 1, L1 and R2 are as defined for formula (I), or any applicable variations detailed herein, may be performed as exemplified below. In some variations, Z is an alkylene moiety and R is hydrogen. In some variations, Z is taken together with the adjacent "NR" group to form a heterocyclic ring.

[0577] N-(((1-acetyl-3-methylazetidin-3-yl)oxy)carbonyl)-O-(trans-3- (2-(5,6,7,8-tetrahydro-1, 8-naphthyridin-2-yl)ethyl)cyclobutyl)methyl homoserinate. To a solution of N-(((3-methylazetidin-3-yl)oxy)carbonyl)-O-(trans-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin Methyl bis(2,2,2-trifluoroacetate) -2-yl)ethyl)cyclobutyl)homoserinate (35.0 mg, 0.05 mmol) and N,N-diisopropylethylamine (52.9 μl, 0.304 mmol) in dichloromethane (2.0 ml) at 0 °C acetic anhydride (8.6 μl, 0.091 mmol) was added. The reaction mixture was removed from the ice bath and allowed to warm to room temperature. After 20 minutes, the reaction mixture was concentrated in vacuo and used without further purification. GENERAL PROCEDURE M

[0578] The following transformation:

[0579] where Z refers to that portion of the molecule that connects the -(O)nC(O)N(H)CH(COOCH3)L1- portion of the molecule with the remainder of the chemical portion R2, where n is 0 or 1, L1 and R2 are as defined for formula (I), or any applicable variations detailed herein, may be performed as exemplified below. In some variations, Z is an alkylene moiety and R is hydrogen. In some variations, Z is taken together with the adjacent "NR" group to form a heterocyclic ring.

[0580] N-(((3-methyl-1-(methylsulfonyl)azetidin-3-yl)oxy)carbonyl)-O- (trans-3-(2-(5,6,7,8-tetrahydro -1,8-naphthyridin-2- yl)ethyl)cyclobutyl)methyl homoserinate. To a solution of N-(((3-methylazetidin-3-yl)oxy)carbonyl)-O-(trans-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin -2-yl)ethyl)cyclobutyl)methyl bis(2,2,2-trifluoroacetate) homoserinate (28.0 mg, 0.04 mmol) and N,N-Diisopropylethylamine (42.4 μl, 0.24 mmol) in dichloromethane (2.0 ml) at 0 °C methanesulfonyl chloride (5.6 μl, 0.073 mmol) was added. The reaction mixture was removed from the ice bath and allowed to warm to room temperature. After 20 minutes, the reaction mixture was concentrated in vacuo and used without further purification.

[0581] N-(4-cyano-2,6-dimethylbenzoyl)-O-(cis-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl) ethyl)cyclobutyl)homoserine. To a solution of N-(4-cyano-2,6-dimethylbenzoyl)-O-(cis-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl Methyl)ethyl)cyclobutyl)homoserinate (427 mg, 0.846 mmol) in THF/MeOH/H2O 3:1:1 was added LiOH (81.0 mg, 3.38 mmol). The reaction was allowed to stir at room temperature for 4 hours. LCMS showed conversion to product and the reaction mixture was diluted with water and purified by reverse phase preparative HPLC to generate N-(4-cyano-2,6-dimethylbenzoyl)-O-(cis-3-(2-( 5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine as a salt of TFA. GENERAL PROCEDURE

[0582] Synthesis of 7-(4-oxobutyl)-3,4-dihydro-1,8-naphthyridine-1(2H)- tert-butyl carboxylate

[0583] 7-(4-ethoxy-4-oxobutyl)-3,4-dihydro-1,8-naphthyridine-1(2H)-tert-butyl carboxylate. To a solution of ethyl 4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butanoate (5.25 g, 21.1 mmol) and di-tert dicarbonate butyl (5.89 ml, 25.4 mmol) in THF (70 ml) was added lithium bis(trimethylsilyl)amide (25.4 ml, 25.4 mmol) at 0°C. After 2 hours, the reaction was diluted with EtOAc (50 ml) and quenched with saturated NH4Cl (50 ml). After 30 min of stirring, the layers were separated and the organic layer was washed with brine (20 ml), dried over Na2SO4 and concentrated in vacuo. The resulting crude residue was purified by normal-phase chromatography on silica gel to provide 7-(4-ethoxy-4-oxobutyl)-3,4-dihydro-1,8-naphthyridine-1(2H)-tert carboxylate. -butyl.

[0584] 7-(4-hydroxybutyl)-3,4-dihydro-1,8-naphthyridine-1(2H)-tert-butyl carboxylate. To a solution of tert-butyl 7-(4-ethoxy-4-oxobutyl)-3,4-dihydro-1,8-naphthyridine-1(2H)-carboxylate (6.81 g, 19.5 mmol ) in THF (50 ml) LiBH4 (at 1.0 M in THF, 19.5 ml, 19.5 mmol) was added at room temperature. The mixture was stirred overnight and then quenched with saturated NH4Cl solution and diluted with EtOAc. The layers were separated and the aqueous layer was extracted with EtOAc. The combined organic extracts were washed with H2O, dried over Na2SO4, filtered and concentrated in vacuo. The resulting crude residue was purified by normal phase chromatography on silica gel to give tert-butyl 7-(4-hydroxybutyl)-3,4-dihydro-1,8-naphthyridine-1(2H)-carboxylate.

[0585] 7-(4-oxobutyl)-3,4-dihydro-1,8-naphthyridine-1(2H)-tert-butyl carboxylate. A solution of oxalyl chloride (2.57 ml, 29.3 mmol) in CH2Cl2 (69 ml) was cooled to -78°C for 5 minutes, at which time dimethylsulfoxide (4.2 ml, 58.6 mmol) was added and the mixture was stirred for 30 min. A solution of tert-butyl 7-(4-hydroxybutyl)-3,4-dihydro-2H-1,8-naphthyridine-1-carboxylate (6.9 g, 22.6 mmol) in CH2Cl2 (10. 5 ml) was added and stirred at -78°C for 1 h. Triethylamine (10.5 ml, 75.1 mmol) was then added to the reaction mixture and stirred for 30 minutes. The reaction was quenched with water and extracted with CH2Cl2. The organic layer was collected and dried over sodium sulfate. The organic layer was concentrated to provide tert-butyl 7-(4-oxobutyl)-3,4-dihydro-1,8-naphthyridine-1(2H)-carboxylate which was used without further purification. GENERAL PROCEDURE

[0586] Synthesis of 3-(thiazol-5-yl)benzoic acid

[0587] Methyl 3-(thiazol-5-yl)benzoate. A microwave flask was charged with (3-(methoxycarbonyl)phenyl)boronic acid (513 mg, 2.85 mmol), 5-bromothiazole (513 mg, 3.13 mmol) and Pd(PPh3)4 (132 mg, 0.11 mmol) and then diluted with dioxane (5 ml) and 2 M aqueous solution of K2CO3 (4.25 ml). The mixture was degassed by bubbling N2 through the solution while stirring vigorously at room temperature and then sealed and heated at 100 °C for 30 min. The reaction mixture was cooled to room temperature and diluted with EtOAc and H2O. The layers were separated and the organic layer was dried over Na2SO4, filtered and concentrated in vacuo. The crude residue was purified by normal phase chromatography on silica gel to provide methyl 3-(thiazol-5-yl)benzoate.

[0588] 3-(thiazol-5-yl)benzoic acid. To a mixture of methyl 3-(thiazol-5-yl)benzoate (600 mg, 2.74 mmol) in THF/MeOH/H2O 4:1:1 (6 ml) was added LiOH (98 mg, 4. 10 mmol) and the resulting mixture was stirred at room temperature for 3 hours. The mixture was partially concentrated in vacuum to remove volatile organics and then acidified with 1 M HCl to pH = 1 causing a precipitate to form. The suspension was filtered and the solid that was collected was washed with H2O and dried under high vacuum to generate 3-(thiazol-5-yl)benzoic acid. GENERAL PROCEDURE Q SYNTHESIS OF RACEMIC TRANS-2-(3,5-DIMETHYL-1H-PYRAZOLE-1-YL) CYCLOPENTAN-1-OL

[0589] trans-2-(3,5-dimethyl-1H-pyrazol-1-yl)cyclopentan-1-ol (racemic). To a solution of cyclopentene oxide (2.03 g, 24.1 mmol) in MeCN (10 ml) was added 3,5-dimethyl-1H-pyrazole (2.78 g, 28.96 mmol), then Cs2CO3 (9.43 g, 28.96 mmol) and the resulting mixture was heated at reflux for 16 hours. The reaction mixture was allowed to cool to room temperature and then filtered and concentrated in vacuo. The crude residue was purified by normal phase chromatography on silica gel to provide trans-2-(3,5-dimethyl-1H-pyrazol-1-yl)cyclopentan-1-ol (racemic). GENERAL PROCEDURE R PREPARATION OF 3-HYDROXY-3-(4-ISOPROPYPHENYL)AZETIDINE-1-TERC-BUTYL CARBOXYLATE

[0590] tert-butyl 3-hydroxy-3-(4-isopropylphenyl)azetidine-1-carboxylate. To a solution of tert-butyl 3-oxoazetidine-1-carboxylate (793 mg, 4.63 mmol) in THF (4 ml) at -78°C was added (4-isopropylphenyl)magnesium bromide (at 0.5 M in THF, 5 ml, 5.0 mmol) dropwise and the resulting mixture was stirred for 30 minutes at -78°C. The mixture was diluted with aqueous NH4Cl solution and extracted with EtOAc. The combined organic extracts were dried over Na2SO4, filtered and concentrated in vacuo. The crude residue was purified by normal phase chromatography on silica gel to provide tert-butyl 3-hydroxy-3-(4-isopropylphenyl)azetidine-1-carboxylate.

SYNTHETIC EXAMPLES

[0591] The chemical reactions in the Synthetic Examples described can be easily adapted to prepare a number of other compounds of the invention, and alternative methods for preparing the compounds of this invention are considered to be within the scope of this invention. For example, the synthesis of compounds not exemplified in accordance with the invention can be successfully carried out by modifications apparent to those skilled in the art, for example, by appropriately protecting interfering groups, using other suitable reagents known in the art in addition to those described, or by making modifications routine under reaction conditions. Alternatively, other reactions disclosed herein or known in the art will be recognized as having applicability to prepare other compounds of the invention. In the following examples, certain compounds are indicated as racemic, as separate isomers, or with unassigned absolute stereochemistry at some stereocenters, and the like. For some compounds, additional separation of isomers and/or assignment of absolute stereochemistry was performed. The assigned stereochemistry of such compounds is shown in the structures as depicted in Figure 1, Table 2. EXAMPLE 1, COMPOUND 1 TWO SYNTHESES OF N-(2-CHLORO-3-FLUOROBENZOYL)-O-(4- (5,6,7 ,8-TETRAHYDRO-1,8-NAPHTHYRIDIN-2-YL)BUTYL)HOMOSERINE EXAMPLE 1st

[0592] Compound 1a-a: A solution of tert-butyl 7-(4-hydroxybutyl)-3,4-dihydro-2H-1,8-naphthyridine-1-carboxylate (11 g, 35.90 mmol) in DMF (150 ml) was added NaH (2.15 g, 53.85 mmol, 60% suspension in mineral oil) at 0 °C under N2. The mixture was stirred for 30 min at 0°C, then 3-bromoprop-1-ene (5.21 g, 43.08 mmol, 1.2 eq) was added to the mixture at 0°C. The mixture was stirred for 10 hours at 20°C. TLC (Petroleum ether/ethyl acetate = 3/1, Rf = 0.1) indicated that 7-(4-hydroxybutyl)-3,4-dihydro-2H-1,8-naphthyridine-1-carboxylate tert-butyl (11 g, 35.90 mmol) was completely consumed. LCMS indicated that the desired M+H+ was detected. The mixture was quenched with NH4Cl solution and extracted with EtOAc (3 x 50 ml). The organic layer was dried with brine and Na2SO4 and concentrated under reduced pressure to give a residue. The crude product was purified by column chromatography (SiO2, Petroleum ether/ethyl acetate = 50/1 to 5:1) to give compound 1a-a (6 g, 16.64 mmol, 46.36% yield) as a colorless oil. LCMS (ESI+): m/z = 347.3 (M+H)+, RT = 0.943 min.

[0593] 1H NMR (400 MHz, CDCl3) δ ppm 7.29 (s, 1 H) 6.82 (d, J=7.50 Hz, 1 H) 5.92 (td, J=11.19 , 5.18 Hz, 1 H) 5.11- 5.32 (m, 2 H) 3.96 (br d, J=5.51 Hz, 2 H) 3.75 (t, J=5.95 Hz, 2 H) 3.47 (t, J=6.50 Hz, 2 H) 2.70 - 2.77 (m, 4 H) 1.89 - 1.95 (m, 2 H) 1.81 (br t, J=7.83 Hz, 2 H) 1.64 - 1.72 (m, 2 H) 1.52 (s, 9 H).

[0594] Compound 1a-b: To a solution of compound 1a-a (3 g, 8.66 mmol) in MeOH (25 ml) and H2O (25 ml) at 20°C was added NaIO4 (4.63 g, 21.65 mmol, 1.2 ml) and OsO4 (44.03 mg, 173.18 umol, 8.99 ul). The resulting suspension was stirred at 20°C for 10 hours. TLC (Petroleum ether/ethyl acetate = 1/1, Rf = 0.6) indicated that compound 1a-a was completely consumed and a new spot was detected. The mixture was quenched with Na2SO3 solution (150 ml) and extracted by EtOAc (3 x 60 ml). The organic layer was dried with brine and Na2SO4, filtered and concentrated under reduced pressure to give compound 1a-b (2.7 g, 7.75 mmol, 89.5% yield) as a yellow oil. The crude product was used directly for the next step without further purification.

[0595] 1H NMR (400 MHz, CDCl3) δ ppm 9.73 (s, 1 H) 7.29 (br d, J=7.72 Hz, 1 H) 6.80 - 6.83 (m, 1 H) 3.74 (br d, J=5.95 Hz, 2 H) 3.57 (br t, J=6.39 Hz, 2 H) 3.44 - 3.49 (m, 2 H) 2.72 (br t, J=6.28 Hz, 4 H) 1.90 - 1.94 (m, 2 H) 1.70 - 1.84 (m, 4 H) 1.52 (s, 9 H)

[0596] Compound 1a-c: To a solution of compound 1a-b (2.7 g, 7.75 mmol) in DCM (30 ml) was added methyl 2-(benzyloxycarbonylamino)-2-dimethoxyphosphoryl-acetate (2 .82 g, 8.52 mmol) followed by DBU (1.30 g, 8.52 mmol, 1.28 ml). The resulting suspension was stirred at 20°C for 1 hour. TLC (Petroleum ether/ethyl acetate = 1/1, Rf = 0.26) indicated that compound 1a-b was completely consumed and a new major spot was detected. The mixture was quenched with NH4Cl solution and extracted with EtOAc (3 x 40 ml). The organic layer was dried with brine and Na2SO4 and concentrated under reduced pressure to give a residue. The crude product was purified by column chromatography (SiO2, Petroleum ether/ethyl acetate = 10/1 to 1:1). The compound product 1a-c (3 g, 5.42 mmol, 94.40% yield) was obtained as a brown oil.

[0597] 1H NMR (400 MHz, CDCl3) δ ppm 7.32 - 7.39 (m, 5 H) 6.80 (d, J=7.50 Hz, 1 H) 6.68 (br s, 1 H) 6.57 (t, J=5.62 Hz, 1 H) 5.14 (s, 2 H) 4.15 (d, J=5.51 Hz, 2 H) 3.79 (s, 3 H) 3.74 (d, J=5.95 Hz, 2 H) 3.47 (t, J=6.50 Hz, 2 H) 2.70 - 2.75 (m, 4 H) 1, 92 (quin, J=6.34 Hz, 2 H) 1.76 - 1.84 (m, 2 H) 1.63 - 1.68 (m, 2 H) 1.52 (s, 10 H).

[0598] Compound 1a-d: The solvent MeOH (30 ml) was added Pd(OH)2/C (507.31 mg, 722.48 umol, 20% purity) and degassed under vacuum and purged with H2 several times . The mixture was stirred under H2 (0.34 MPa (50 psi)) at 50°C for 4 hours. Then, compound 1a-c (2 g, 3.61 mmol) was added to the mixture. The suspension was degassed under vacuum and purged with H2 three times. The mixture was stirred under H2 (0.34 MPa (50 psi)) at 50°C for 4 hours. LCMS indicated that the desired MS was detected. The mixture was filtered and concentrated under reduced pressure. The compound product 1a-d (1.4 g, crude) was obtained as a yellow oil, which was used in the next step without further purification. LCMS (ESI+): m/z = 422.3 (M+H)+; RT= 0.752 min.

[0599] Compound 1a-e: To a mixture of 2-chloro-3-fluorobenzoic acid (807.50 mg, 4.63 mmol) in DMF (15 ml) was added HOBt (721.25 mg, 5. 34 mmol), EDCI (1.02 g, 5.34 mmol)) and DIEA (1.38 g, 10.68 mmol, 1.86 ml). Then, compound 1a-d (1.5 g, 3.56 mmol) was added to the mixture. The mixture was stirred at 20°C for 5 hours. TLC (Petroleum ether/ethyl acetate = 0/1, Rf = 0.2) indicated that compound 1a-d was completely consumed. The mixture was extracted by H2O (40 ml) and EtOAc (3 x 20 ml). The organic layer was dried with brine and Na2SO4, filtered and concentrated under reduced pressure. The crude product was purified by preparative HPLC (neutral conditions) to give compound 1a-e (1.3 g, 2.2 mmol, 61.69% yield, 97.61% purity) as a brown oil. HPLC purification conditions: column: Phenomenex Gemini C18 250 x 50 mm x 10 µm; mobile phase: [water (10 mM NH4HCO3)-ACN]; B%: 40% to 70%, 20 min. LCMS (ESI+): m/z = 578.4 (M+H)+; RT= 1.038 min.

[0600] Example 1a: To a mixture of compound 1a-e (500 mg, 864.94 umol) HCl (at 4 M, 3.24 ml, 15 eq) was added. The mixture was stirred at 70°C for 10 hours. LCMS indicated that the desired M+H+ was detected. The mixture was lyophilized directly to generate Example 1a (304.47 mg, 587.12 umol, 67.88% yield, 96.492% purity, HCl) which was delivered without any further purification. LCMS (ESI+): m/z = 464.1 (M+H)+, RT = 2,450 min; HPLC purity: 96.492%, RT = 6.566 min; Chiral SFC purity: 52.72%, ee value: 0%, RT = 3.447 min.

[0601] 1H NMR (400 MHz, MeOH-d4) δ ppm 7.57 (d, J=7.28 Hz, 1 H) 7.32 - 7.47 (m, 3 H) 6.65 (d , J=7.28 Hz, 1 H) 3.54 - 3.64 (m, 3 H) 3.43 - 3.50 (m, 3 H) 2.80 (t, J=6.28 Hz, 2 H) 2.70 - 2.77 (m, 2 H) 2.29 (ddt, J=14.08, 9.40, 4.80, 4.80 Hz, 1 H) 1.62 - 2, 00 (m, 8H). EXAMPLE 1B

[0602] Compound 1b-a: A suspension of 4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butanoic acid hydrochloride (1.23 g, 4.79 mmol, 1.0 equiv) in THF was added LiAlH4 (at 1.0 M in THF, 10.6 ml, 10.6 mmol) dropwise and the resulting mixture was refluxed overnight. The mixture was then cooled in an ice bath and to this was slowly added H2O (400 μl), then 1.0 M aqueous NaOH (400 μl), then H2O (400 μl) again and stirred for 15 minutes and then a Large excess MgSO4 was added and stirred for an additional 30 minutes. The resulting organic mixture was filtered and then concentrated in vacuo to provide compound 1b-a.

[0603] Compound 1b-b: To a stirring suspension of NaH (dispersion of 60% by weight in mineral oil, 238 mg, 5.96 mmol) in THF (8.2 ml) at 0 ° C was added a solution of 1b-a (820 mg, 3.98 mmol)) in THF (4.1 ml) dropwise. After completion of the addition, the ice bath was removed and the resulting mixture was stirred at room temperature for 30 minutes, at which time allyl bromide (400 μl, 4.62 mmol) was added dropwise. The suspension was stirred for a further 6 hours at room temperature and then carefully diluted with H2O and EtOAc. The layers were separated and the aqueous layer was extracted with EtOAc. The combined organic extracts were dried over MgSO4, filtered and concentrated in vacuo. The crude residue was purified by silica gel chromatography to compound 1b-b.

[0604] Compound 1b-c: to a solution of 1b-b (582 mg, 2.36 mmol) in THF/H2O 3:1 (6 ml) at room temperature was added NaIO4 (2.02 g, 9. 44 mmol) followed by OsO4 (2.5 wt% in t-BuOH, 480 μl, 0.05 mmol). The resulting suspension was stirred at room temperature for 5 hours and then diluted with 1:1 saturated aqueous NaHCO3/saturate aqueous Na2S2O3 and EtOAc solution and then stirred for 1 hour at room temperature. The two-phase mixture was filtered through a small pad of Celite and the layers were separated. The aqueous layer was extracted with DCM and the combined organic extracts were dried over MgSO4, filtered and concentrated in vacuo to provide the title compound which was used without further purification.

[0605] To the crude residue obtained from the previous reaction (586 mg, 2.36 mmol) in CH2Cl2 (6 ml) at room temperature was added methyl 2-(((benzyloxy)carbonyl)amino)-2-(dimethoxyphosphoryl)acetate (860 mg, 2.60 mmol) followed by DBU (391 μl, 2.60 mmol) and stirred for 30 minutes at room temperature. The mixture was diluted with aqueous NH4Cl solution and stirred for 5 minutes at room temperature. The layers were separated and the aqueous layer was extracted with EtOAc. The combined organic extracts were dried over MgSO4, filtered and concentrated in vacuo. The crude residue was purified by silica gel chromatography to provide compound 1b-c.

[0606] Compound 1b-d: A vial containing 1b-c (497 mg, 1.10 mmol) and 20% by weight of Pd(OH)2 on carbon (100 mg) was diluted with MeOH (5 ml) and, then evacuated and filled with H2 for 3 cycles and then stirred under an H2 atmosphere for 3 hours. The resulting mixture was filtered through a pad of Celite and then concentrated in vacuo to give compound 1b-d (352 mg) which was used without further purification.

[0607] Compound 1b-e: A vial containing 1b-d (50.0 mg, 0.15 mmol) was charged with 2-chloro-3-fluorobenzoic acid (40.7 mg, 0.23 mmol) and then diluted with THF/DMF 10:1 (2.0 ml). To this was then added DIPEA (81 μl, 0.47 mmol) followed by HATU (89 mg, 0.23 mmol) and stirred for 30 minutes at room temperature and then concentrated in vacuo. The crude residue was purified by silica gel chromatography to compound 1b-e.

[0608] Example 1b: To a solution of 1b-e (61 mg, 0.13 mmol) in THF/MeOH/H2O 4:1:1 (2.0 ml) was added LiOH (9 mg, 0.39 mmol) and the resulting mixture was stirred at room temperature for 30 minutes. The mixture was then neutralized with AcOH and purified by preparative reverse phase HPLC to provide Example 1b as the trifluoroacetate salt. LCMS theoretical m/z = 464.9 [M+H]+, found 464.9. EXAMPLE 2, COMPOUND 8 2-(2-ETHYLBUTANAMIDO)-5-(3-(5,6,7,8-TETRAHYDRO-1,8-NAPHTHYRIDIN-2-YL)PROPOXY)PENTANOIC ACID

[0609] Compound 2a: two batches in parallel: A mixture of ethyl 4-oxopentanoate (50 g, 346.82 mmol, 49.50 ml) and 2-aminopyridine-3-carbaldehyde (42.35 g, 346. 82 mmol) in EtOH (800 ml) was added L-proline (19.96 g, 173.41 mmol). The mixture was refluxed at 85°C for 12 hours. LCMS indicated that the reaction was complete. TLC (petroleum ether/ethyl acetate = 2:1, Rf = 0.31) was the product stain. The mixture was filtered and concentrated under reduced pressure. The mixture was extracted by H2O (1,000 ml) and EtOAc (3 x 800 ml), washed with brine and dried over Na2SO4, filtered and concentrated under reduced pressure. The crude product was purified by column chromatography (SiO2, petroleum ether/ethyl acetate = 10/1 to 1:1) to give compound 2a (60 g, 240.85 mmol, 34.72% yield, 92.4% purity) as a yellow solid. LCMS (ESI+): m/z = 231.1(M+H)+, RT = 0.68 min, 1H NMR (400 MHz, CDCl3) δ ppm 9.08 (dd, J=4.19, 1 .98 Hz, 1 H) 8.07 - 8.19 (m, 2 H) 7.42 - 7.48 (m, 2 H) 4.12 (q, J=7.06 Hz, 2 H) 3 .32 - 3.39 (m, 2 H) 3.06 (t, J=7.28 Hz, 2 H) 1.23 (t, J=7.17 Hz, 3 H).

[0610] compound 2b: two batches were processed in parallel: To a solution of compound 2a (26 g, 112.91 mmol) in EtOH (300 ml) was added Pd/C (3 g, 10%) under N2. The suspension was degassed under vacuum and purged with H2 several times. The mixture was stirred under H2 (0.34 MPa (50 psi)) at 20 °C for 10 hours. TLC (petroleum ether/ethyl acetate = 0:1, Rf = 0.3) indicated that compound 5a was completely consumed and a new spot was detected. LCMS indicated that the desired MS was detected. The mixture was filtered and concentrated under reduced pressure to give compound 2b (46 g, 196.33 mmol, 86.94% yield) as a white solid. The crude product was used in the next step with further purification. LCMS (ESI+): m/z = 235.1 (M+H)+, RT = 0.772 min.

[0611] Compound 2c: A mixture of compound 2b (46 g, 196.33 mmol) and Boc2O (100 ml) was stirred at 40 ° C for 15 hours. TLC (Petroleum ether/ethyl acetate = 2:1, Rf = 0.11) indicated that compound 2c was formed. The mixture was not worked up, but evaporated and applied to a silica gel column. The crude product was purified by column chromatography (SiO2, Petroleum ether/ethyl acetate = 100/1 to 5:1) to give compound 2c (32 g, 95.69 mmol, 48.74% yield) as a white solid. 1H NMR (400 MHz, CDCl3) δ ppm 7.33 (d, J=7.72 Hz, 1 H) 6.88 (d, J=7.72 Hz, 1 H) 4.17 (q, J =7.06 Hz, 2 H) 3.76 - 3.81 (m, 2 H) 3.04 - 3.10 (m, 2 H) 2.81- 2.86 (m, 2 H) 2, 76 (t, J=6.62 Hz, 2 H) 1.95 (quin, J=6.34 Hz, 2 H) 1.51 (s, 9 H) 1.28 (t, J=7.06 Hz, 3H).

[0612] Compound 2d: To a solution of compound 2C (14 g, 41.86 mmol) in THF (140 ml) was added LiBH4 (1.82 g, 83.73 mmol) in several portions at 0 ° C under N2 . The reaction mixture was heated at 15°C for 1 hour. The reaction mixture was stirred at 40 °C for 12 hours. TLC (petroleum ether/ethyl acetate = 1:1, Rf = 0.61) indicated that compound 2c was completely consumed. The mixture was poured into saturated NH4Cl solution (500 ml) and extracted with EtOAc (3 x 300 ml). The organic layer was dried with brine and Na2SO4, filtered and concentrated under reduced pressure. The crude product was purified by column chromatography (SiO2, petroleum ether/ethyl acetate = 0:1) to give compound 2d (18 g, 61.57 mmol, 73.53% yield) as a white solid . 1H NMR (400 MHz, CDCl3) δ ppm 7.31 (d, J=7.72 Hz, 1 H) 6.83 (d, J=7.72 Hz, 1 H) 3.74 - 3.78 (m, 2 H) 3.69 (br t, J=5.62 Hz, 2 H) 2.88 - 2.93 (m, 2 H) 2.73 (t, J=6.50 Hz, 2 H) 1.89 - 1.96 (m, 4 H) 1.54 (s, 9 H).

[0613] Compound 2e: To a mixture of compound 2d (3 g, 10.26 mmol) in DMF (30 ml) was added NaH (2.46 g, 61.57 mmol, 60% purity) at 0 °C . Then the mixture was stirred at 0°C for 0.5 h. Then, 5-bromopent-1-ene (6.12 g, 41.04 mmol) was added to the mixture at 0 °C. The mixture was heated at 15°C for 12 hours. LCMS indicated that the desired MS was detected. TLC (petroleum ether/ethyl acetate = 3/1, Rf = 0.18) indicated that compound 2d was consumed. The mixture was poured into NH4Cl solution (50 ml) and extracted by EtOAc (3 x 30 ml). The organic layer was dried with brine and Na2SO4, filtered and concentrated under reduced pressure. The crude product was purified by column chromatography (SiO2, petroleum ether/ethyl acetate = 100/1 to 10:1) to give compound 2e (2.8 g, 7.77 mmol, 75.70% yield) as a yellow oil. LCMS (ESI+): m/z = 361.3 (M+H)+; RT: 1.016 min, 1H NMR (400 MHz, CDCl3) δ ppm 7.25 (d, J=3.09 Hz, 1 H) 6.80 (d, J=7.72 Hz, 1 H) 5, 80 (ddt, J=17.03, 10.31, 6.61, 6.61 Hz, 1 H) 4.92 - 5.02 (m, 2 H) 3.72 (d, J=5.95 Hz, 2 H) 3.40 - 3.44 (m, 4 H) 2.69 - 2.77 (m, 4 H) 2.08 - 2.13 (m, 2 H) 1.97 - 2, 02 (m, 2 H) 1.88 - 1.92 (m, 2 H) 1.62 - 1.67 (m, 2 H) 1.49 (s, 9 H).

[0614] Compound 2f: Ozone was bubbled into a solution of Compound 2e (2.8 g, 7.77 mmol) in DCM (20 ml) and MeOH (10 ml) at -78 ° C for 30 minutes. After excess O3 was purged by O2, Me2S (4.83 g, 77.67 mmol, 5.70 ml) was added at -78 °C. The mixture was stirred for 12 hours at 20°C. LCMS indicated that the desired MS was detected. TLC (petroleum ether/ethyl acetate = 1:1, Rf = 0.6) indicated that compound 2e was completely consumed. The mixture was concentrated under reduced pressure. The crude product was purified by column chromatography (SiO2, petroleum ether/ethyl acetate = 30:1 to 8:1) to give compound 2f (1.4 g, 3.86 mmol, 49.73% yield) as a brown oil. LCMS (ESI+): m/z = 363.3 (M+H)+; RT = 0.853 min.

[0615] Compound 2g: To a solution of compound 2f (1.4 g, 3.86 mmol, 1 eq) in THF (10 ml) was added 2-methylpropane-2-sulfinamide (514.95 mg, 4.25 mmol) and tetraethoxytitanium (2.64 g, 11.59 mmol, 2.40 ml). The mixture was stirred at 50°C for 12 hours. LCMS indicated the desired MS. The mixture was concentrated under reduced pressure to give compound 2g (1.7 g, crude) as a brown oil. The crude product was used directly for the next step without further purification. LCMS (ESI+): m/z= 466.3 (M+H)+, RT: 0.991 min.

[0616] Compound 2h: To a mixture of compound 2g (1.7 g, 3.65 mmol) in dry THF (20 ml) was added NaCN (536.75 mg, 10.95 mmol). The mixture was stirred at 40°C for 12 hours. NaCN (536.75 mg, 10.95 mmol) and i-PrOH (658.19 mg, 10.95 mmol, 838.46 µl) were added to the mixture with stirring for 16 hours at 55°C. LCMS indicated that the desired M+H was detected. TLC (petroleum ether/ethyl acetate = 1:1, Rf = 0.72) indicated that compound 2g was consumed. The mixture was extracted by H2O (50 ml) and EtOAc (3 x 30 ml). The organic layer was dried with brine and Na2SO4, filtered and concentrated under reduced pressure. The H2O layer was abruptly cooled by NaClO solution. The crude product was purified by column chromatography (SiO2, petroleum ether/ethyl acetate = 10:1 to 1:1) to give compound 2h (450 mg, 850.45 umol, 23.29% yield). like a yellow oil. LCMS (ESI+): m/z= 493.4 (M+H)+, RT= 0.958 min.

[0617] Compound 2i: A mixture of compound 2h (450 mg, 913.38 umol) in HCl/MeOH (5 ml) was stirred at 50 °C for 16 hours. LCMS indicated that the desired MS was detected. The mixture was concentrated under reduced pressure to generate crude compound 2i (360 mg, crude) as a brown oil, which was used directly in the next step without further purification. LCMS (ESI+): m/z= 322.3 (M+H)+, RT= 0.628 min.

[0618] Compound 2j: To a mixture of 2-ethylbutanoic acid (79.53 mg, 684.7 umol, 86.26 uL) in DMF (3 ml) was added HOBt (92.52 mg, 684.70 umol) , EDCI (131.26 mg, 684.7 umol) and DIEA (176.98 mg, 1.37 mmol, 238.52 uL). Then, compound 2i (180 mg, 456.46 umol) was added to the mixture. The mixture was stirred at 15°C for 10 hours. LCMS indicated that the desired MS was detected. The mixture was extracted by H2O (20 ml) and EtOAc (3 x 10 ml). The organic layer was dried with brine and Na2SO4, filtered and concentrated under reduced pressure. The crude product was purified by prep-TLC (SiO2, ethyl acetate/MeOH = 10:1) to give compound 2j (65 mg, 154.93 umol, 33.94% yield) as a yellow oil. LCMS (ESI+): m/z= 419.56 (M+H)+, RT= 0.855 min.

[0619] Example 2: To a mixture of compound 2j (65 mg, 154.92 umol) HCl (4 M, 193.66 ul) was added. The mixture was stirred at 70°C for 12 hours. LCMS indicated that the desired MS was detected. The mixture was concentrated under reduced pressure. The crude product was purified by preparative HPLC (TFA condition) to generate Example 2 (40 mg, 76.13 umol, 49.14% yield, 98.887% purity, TFA) as a colorless oil.

[0620] HPLC purification conditions: column: Luna C18 100 x 30 5u; mobile phase: [water (0.1% TFA)-ACN]; B%: 1% to 40%, 5 min.

[0621] 1H NMR (400 MHz, MeOH-d4) δ ppm 7.59 (d, J=7.50 Hz, 1 H) 6.64 (d, J=7.28 Hz, 1 H) 4, 46 (dd, J=9.26, 4.85 Hz, 1 H) 3.44 - 3.53 (m, 6 H) 2.78 - 2.85 (m, 4 H) 2.14 (tt, J=9.59, 4.96 Hz, 1 H) 1.91- 1.98 (m, 5 H) 1.44 - 1.75 (m, 7 H) 0.87 - 0.95 (m, 6 H); LCMS (ESI+): m/z=406.2(M+H)+, RT= 2.336 min; HPLC purity: 98.887%, RT=6.242 min; Chiral purity of SFC: 52.72%, ee value: 5.44%, RT=2.013 min. EXAMPLE 3, COMPOUND 9 2-(2-CHLORO-3-FLUOROBENZAMIDO)-5-(3-(5,6,7,8-TETRA-HYDRO-1,8-NAPHTHYRIDIN-2-YL)PROPOXY)PENTANOIC ACID

[0622] Example 3 was prepared by the same procedure used to prepare Example 2, with the exception that the acid was replaced by 2-chloro-3-fluorobenzoic acid in the reaction with intermediate 2i.

[0623] HPLC purification conditions: column: Phenomenex Synergi C18 100 * 21.2 mm * 4 um; mobile phase: [water (0.1% TFA) - ACN]; B%: 15% to 45%, 10 min

[0624] 1H NMR (400 MHz, MeOH-d4) δ ppm 7.57 (d, J=7.50 Hz, 1 H) 7.30 - 7.43 (m, 3 H) 6.63 (d , J=7.28 Hz, 1 H) 4.63 (dd, J=9.26, 4.85 Hz, 1 H) 3.47 - 3.52 (m, 6 H) 2.78 - 2, 83 (m, 4 H) 2.01- 2.09 (m, 1 H) 1.92 - 1.97 (m, 4 H) 1.71- 1.87 (m, 3 H); HPLC purity: 99.041%, RT: 6.480 min; LCMS (ESI+): m/z = 464.1 (M+H)+, RT=2.399 min; Chiral purity of SFC: 52.42%, ee value: 4.84%, RT = 3.870 min. EXAMPLE 4, COMPOUND 2

[0625] N-(1-methyl-1H-indazol-4-carbonyl)-O-(4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl)homoserine . Prepared according to General Scheme C using General Procedure I with 1-methyl-1H-indazole-4-carboxylic acid. LCMS theoretical m/z = 466.2. [M+H]+, found 466.2. EXAMPLE 5, COMPOUND 3

[0626] N-(2-ethylbutanoyl)-O-(4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl)homoserine. Prepared according to General Scheme C using General Procedure I with 2-ethylbutanoic acid. LCMS theoretical m/z = 406.3 [M+H]+, found 406.3. EXAMPLE 6, COMPOUND 4

[0627] N-benzoyl-O-(4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl)homoserine. Prepared according to General Scheme C using General Procedure I with benzoic acid. LCMS theoretical m/z = 412.2 [M+H]+, found 412.2. EXAMPLE 7, COMPOUND 5

[0628] N-(4,4-difluorocyclohexane-1-carbonyl)-O-(4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl)homoserine . Prepared according to General Scheme C using General Procedure I with 4,4-difluorocyclohexane-1-carboxylic acid. LCMS theoretical m/z = 454.3; [M+H]+, found 454.3. EXAMPLE 8, COMPOUND 6

[0629] N-pentanoyl-O-(4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl)homoserine. Prepared according to General Scheme C using General Procedure I with butanoic acid. LCMS theoretical m/z = 392.3 [M+H]+, found 392.3. EXAMPLE 9, COMPOUND 7

[0630] N-(3-fluoro-5-(trifluoromethyl)benzoyl)-O-(4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl)homoserine Prepared according to General Scheme C using General Procedure I with 3-fluoro-5-(trifluoromethyl)benzoic acid. LCMS theoretical m/z = 498.2 [M+H]+, found 498.2. EXAMPLE 10, COMPOUND 15 HO O

[0631] N-(3-fluoro-5-(trifluoromethyl)benzoyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl )cyclobutyl)homoserine. Prepared according to General Scheme H using General Procedure I with 3-fluoro-5-(trifluoromethyl)benzoic acid. LCMS theoretical m/z = 524.2 [M+H]+, found 524.3. EXAMPLE 11, COMPOUND 18

[0632] N-pentanoyl-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine. Prepared according to General Scheme H using General Procedure I with pentanoic acid. LCMS theoretical m/z = 418.3 [M+H]+, found 418.3. EXAMPLE 12, COMPOUND 19

[0633] N-(tert-butoxycarbonyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine. Prepared according to General Scheme H to intermediate 13H, followed by General Procedure N. Theoretical LCMS m/z = 434.3 [M+H]+, found 434.3. EXAMPLE 12A, COMPOUND 19

[0634] N-(tert-butoxycarbonyl)-O-(trans-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine. Prepared according to General Scheme A through intermediate 13A, followed by General Procedure N. Theoretical LCMS m/z = 434.3 [M+H]+, found 434.3. EXAMPLE 13, COMPOUND 22

[0635] N-(tert-butoxycarbonyl)-O-(4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl)homoserine. Prepared according to General Scheme C to intermediate 7C, followed by General Procedure N. Theoretical LCMS m/z = 408.2 [M+H]+, found: 408.2. EXAMPLE 14, COMPOUND 14

[0636] N-(2-chloro-3-fluorobenzoyl)-O-(cis-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl) cyclobutyl)homoserine. Prepared according to General Scheme B using General Procedure I with 2-chloro-3-fluorobenzoic acid. LCMS theoretical m/z = 490.2 [M+H]+, found 490.2. EXAMPLE 15, COMPOUND 24

[0637] N-(4-fluorobenzoyl)-O-(cis-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine. Prepared according to General Scheme B using General Procedure I with 4-fluorobenzoic acid. LCMS theoretical m/z = 456.2 [M+H]+, found 456.2. EXAMPLE 16, COMPOUND 24

[0638] N-(4-fluorobenzoyl)-O-(trans-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine. Prepared according to General Scheme A using General Procedure I with 4-fluorobenzoic acid. LCMS theoretical m/z = 456.2 [M+H]+, found 456.2. EXAMPLE 17, COMPOUND 25

[0639] N-(4-chlorobenzoyl)-O-(trans-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine. Prepared according to General Scheme A using General Procedure I with 4-chlorobenzoic acid. LCMS theoretical m/z = 472.2 [M+H]+, found 472.2. EXAMPLE 18, COMPOUND 19 \,O^HI HN

[0640] N-(tert-butoxycarbonyl)-O-(cis-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine. The E2 isomer was used in General Procedure N. LCMS theoretical m/z = 434.3 [M+H]+, found 434.3. EXAMPLE 19, COMPOUND 26

[0641] N-(3-fluorobenzoyl)-O-(trans-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine. Prepared according to General Scheme A using General Procedure I with 3-fluorobenzoic acid. LCMS theoretical m/z = 456.2 [M+H]+, found 456.2. EXAMPLE 20, COMPOUND 27

[0642] N-(3-chlorobenzoyl)-O-(trans-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine. Prepared according to General Scheme A using General Procedure I with 3-chlorobenzoic acid. LCMS theoretical m/z = 472.2 [M+H]+, found 472.2. EXAMPLE 21, COMPOUND 28

[0643] N-(2-chlorobenzoyl)-O-(trans-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine. Prepared according to General Scheme A using General Procedure I with 2-chlorobenzoic acid. LCMS theoretical m/z = 472.2 [M+H]+, found 472.2. EXAMPLE 22, COMPOUND 29

[0644] N-(2-fluorobenzoyl)-O-(trans-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine. Prepared according to General Scheme A using General Procedure I with 2-fluorobenzoic acid. LCMS theoretical m/z = 456.2 [M+H]+, found 456.2. EXAMPLE 23, COMPOUND 30

[0645] N-(2,3-difluorobenzoyl)-O-(trans-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl) homoserine. Prepared according to General Scheme A using General Procedure I with 2,3-difluorobenzoic acid. LCMS theoretical m/z = 474.2 [M+H]+, found 474.2. EXAMPLE 24, COMPOUND 31

[0646] N-(2,4-difluorobenzoyl)-O-(trans-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl) homoserine. Prepared according to General Scheme A using General Procedure I with 2,4-difluorobenzoic acid. LCMS theoretical m/z = 474.2 [M+H]+, found 474.2. EXAMPLE 25, COMPOUND 32

[0647] N-(2-chloro-4-fluorobenzoyl)-O-(trans-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl) cyclobutyl)homoserine. Prepared according to General Scheme A using General Procedure I with 2-chloro-4-difluorobenzoic acid. LCMS theoretical m/z = 490.2 [M+H]+, found 490.2. EXAMPLE 26, COMPOUND 33 CL

[0648] N-(3-chloro-5-fluorobenzoyl)-O-(trans-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl) cyclobutyl)homoserine. Prepared according to General Scheme A using General Procedure I with 3-chloro-5-fluorobenzoic acid. LCMS theoretical m/z = 490.2 [M+H]+, found 490.2. EXAMPLE 27, COMPOUND 34 ci

[0649] N-(3-chloro-2-fluorobenzoyl)-O-(trans-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl) cyclobutyl)homoserine. Prepared according to General Scheme A using General Procedure I with 3-chloro-2-fluorobenzoic acid. LCMS theoretical m/z = 490.2 [M+H]+, found 490.2. EXAMPLE 28, COMPOUND 35 F

[0650] N-(3,5-difluorobenzoyl)-O-(trans-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl) homoserine. Prepared according to General Scheme A using General Procedure I with 3,5-difluorobenzoic acid. LCMS theoretical m/z = 474.2 [M+H]+, found 474.2. EXAMPLE 29, COMPOUND 36 HO O

[0651] N-(3,4-difluorobenzoyl)-O-(trans-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl) homoserine. Prepared according to General Scheme A using General Procedure I with 3,4-difluorobenzoic acid. LCMS theoretical m/z = 474.2 [M+H]+, found 474.2. EXAMPLE 30, COMPOUND 37 H ISL ,N HO O

[0652] N-(2,3-dichlorobenzoyl)-O-(trans-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl) homoserine. Prepared according to General Scheme A using General Procedure I with 2,3-dichlorobenzoic acid. LCMS theoretical m/z = 506.2 [M+H]+, found 506.2. EXAMPLE 31, COMPOUND 38 F HN HO O

[0653] N-(2-chloro-6-fluorobenzoyl)-O-(trans-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl) cyclobutyl)homoserine. Prepared according to General Scheme A using General Procedure I with 2-chloro-5-fluorobenzoic acid. LCMS theoretical m/z = 490.2 [M+H]+, found 490.2. EXAMPLE 32, COMPOUND 39

[0654] N-(2,6-difluorobenzoyl)-O-(trans-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl) homoserine. Prepared according to General Scheme A using General Procedure I with 2,6-difluorobenzoic acid. LCMS theoretical m/z = 474.2 [M+H]+, found 474.2. EXAMPLE 33, COMPOUND 40

[0655] N-(2,5-difluorobenzoyl)-O-(trans-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl) homoserine. Prepared according to General Scheme A using General Procedure I with 2,5-difluorobenzoic acid. LCMS theoretical m/z = 474.2 [M+H]+, found 474.2. EXAMPLE 34, COMPOUND 41

[0656] N-(3,4-dichlorobenzoyl)-O-(trans-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl) homoserine. Prepared according to General Scheme A using General Procedure I with 3,4-dichlorobenzoic acid. LCMS theoretical m/z = 506.2 [M+H]+, found 506.2. EXAMPLE 35, COMPOUND 42

[0657] N-picolinoyl-O-(trans-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine. Prepared according to General Scheme A using General Procedure I with picolinic acid. LCMS theoretical m/z = 439.2 [M+H]+, found 439.2. EXAMPLE 36, COMPOUND 43

[0658] N-nicotinoyl-O-(trans-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine. Prepared according to General Scheme A using General Procedure I with nicotinic acid. LCMS theoretical m/z = 439.2 [M+H]+, found 439.3. EXAMPLE 37, COMPOUND 44

[0659] N-isonicotinoyl-O-(trans-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine. Prepared according to General Scheme A using General Procedure I with isonicotinic acid. LCMS theoretical m/z = 439.2 [M+H]+, found 439.3. EXAMPLE 38, COMPOUND 45

[0660] N-(1-methyl-1H-indazol-4-carbonyl)-O-(trans-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2- yl)ethyl)cyclobutyl)homoserine. Prepared according to General Scheme A using General Procedure I with 1-methyl-1H-indazole-4-carboxylic acid. LCMS theoretical m/z = 492.3 [M+H]+, found 492.3. EXAMPLE 39, COMPOUND 46 HO O

[0661] N-(2-methyl-2H-indazol-6-carbonyl)-O-(trans-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2- yl)ethyl)cyclobutyl)homoserine. Prepared according to General Scheme A using General Procedure I with 2-methyl-2H-indazole-6-carboxylic acid. LCMS theoretical m/z = 492.3 [M+H]+, found 492.3. EXAMPLE 40, COMPOUND 47 \NN' HO O

[0662] N-(2-methyl-2H-indazol-5-carbonyl)-O-(trans-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2- yl)ethyl)cyclobutyl)homoserine. Prepared according to General Scheme A using General Procedure I with 2-methyl-2H-indazole-5-carboxylic acid. LCMS theoretical m/z = 492.3 [M+H]+, found 492.3. EXAMPLE 41, COMPOUND 48

[0663] N-(1-methyl-1H-pyrrolo[2,3-b]pyridine-4-carbonyl)-O-(trans- 3-(2-(5,6,7,8-tetrahydro- 1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine. Prepared according to General Scheme A using General Procedure I with 1-methyl-1H-pyrrolo[2,3-b]pyridine-4-carboxylic acid. LCMS theoretical m/z = 492.3 [M+H]+, found 492.3. EXAMPLE 42, COMPOUND 49

[0664] N-((R)-3-hydroxy-2-phenylquinolinayl)-O-(trans-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2- yl)ethyl)cyclobutyl)homoserine. Prepared according to General Scheme A using General Procedure I with (R)-3-hydroxy-2-phenylpropanoic acid and General Procedure N followed by preparative HPLC to provide the first elution of two diastereomers as a single stereoisomer. The stereochemistry of the amino acid has not been assigned. LCMS theoretical m/z = 482.3 [M+H]+, found 482.3. EXAMPLE 43, COMPOUND 49

[0665] N-((R)-3-hydroxy-2-phenylquinolinayl)-O-(trans-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2- yl)ethyl)cyclobutyl)homoserine. Prepared according to General Scheme A using General Procedure I with (R)-3-hydroxy-2-phenylpropanoic acid and General Procedure N followed by preparative HPLC to provide second elution of two diastereomers as a single stereoisomer. The stereochemistry of the amino acid has not been assigned. LCMS theoretical m/z = 482.3 [M+H]+, found 482.3. EXAMPLE 44, COMPOUND 50

[0666] N-(2-ethylbutanoyl)-O-(trans-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine. Prepared according to General Scheme A using General Procedure I with 2-ethylbutanoic acid. LCMS theoretical m/z = 432.3 [M+H]+, found 432.3. EXAMPLE 45, COMPOUND 51

[0667] N-(3-ethylpentanoyl)-O-(trans-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine. Prepared according to General Scheme A using General Procedure I with 3-ethylpentanoic acid. LCMS theoretical m/z = 446.3 [M+H]+, found 446.3. EXAMPLE 46, COMPOUND 49

[0668] N-((S)-3-hydroxy-2-phenylquinolinayl)-O-(trans-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2- yl)ethyl)cyclobutyl)homoserine. Prepared according to General Scheme A using General Procedure I with (S)-3-hydroxy-2-phenylpropanoic acid and General Procedure N followed by preparative HPLC to provide the first elution of two diastereomers as a single stereoisomer. The stereochemistry of the amino acid has not been assigned. LCMS theoretical m/z = 482.3 [M+H]+, found 482.3. EXAMPLE 47, COMPOUND 49

[0669] N-((S)-3-hydroxy-2-phenylquinolinayl)-O-(trans-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2- yl)ethyl)cyclobutyl)homoserine. Prepared according to General Scheme A using General Procedure I with (S)-3-hydroxy-2-phenylpropanoic acid and General Procedure N followed by preparative HPLC to provide second elution of two diastereomers as a single stereoisomer. The stereochemistry of the amino acid has not been assigned. LCMS theoretical m/z = 482.3 [M+H]+, found 482.3. EXAMPLE 48, COMPOUND 52

[0670] N-(1-methyl-1H-pyrrolo[2,3-b]pyridine-5-carbonyl)-O-(trans- 3-(2-(5,6,7,8-tetrahydro- 1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine. Prepared according to General Scheme A using General Procedure I with 1-methyl-1H-pyrrolo[2,3-b]pyridine-5-carboxylic acid. LCMS theoretical m/z = 492.3 [M+H]+, found 492.3. EXAMPLE 49, COMPOUND 53

[0671] O-(trans-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)-N-(3-(thiazol-5 -yl)benzoyl)homoserine. Prepared according to General Scheme A using General Procedure I with 3-(thiazol-5-yl)benzoic acid. LCMS theoretical m/z = 521.2 [M+H]+, found 521.2. EXAMPLE 50, COMPOUND 54

[0672] N-(3-(hydroxymethyl)benzoyl)-O-(trans-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl )homoserine. Prepared according to General Scheme A using General Procedure I with 3-(hydroxymethyl)benzoic acid. LCMS theoretical m/z = 468.2. [M+H]+, found 468.3. EXAMPLE 51, COMPOUND 55

[0673] N-(quinoline-5-carbonyl)-O-(trans-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl) homoserine. Prepared according to General Scheme A using General Procedure I with quinoline-5-carboxylic acid. LCMS theoretical m/z = 489.2. [M+H]+, found 489.3. EXAMPLE 52, COMPOUND 56

[0674] N-(2-cyclopropylbenzoyl)-O-(trans-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine. Prepared according to General Scheme A using General Procedure I with 2-cyclopropylbenzoic acid. LCMS theoretical m/z = 478.3. [M+H]+, found 478.3. EXAMPLE 53, COMPOUND 57

[0675] N-(quinoline-7-carbonyl)-O-(trans-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl) homoserine. Prepared according to General Scheme A using General Procedure I with quinoline-7-carboxylic acid. LCMS theoretical m/z = 489.2. [M+H]+, found 489.3. EXAMPLE 54, COMPOUND 58

[0676] N-(quinoline-6-carbonyl)-O-(trans-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl) homoserine. Prepared according to General Scheme A using General Procedure I with quinoline-6-carboxylic acid. LCMS theoretical m/z = 489.2. [M+H]+, found 489.3. EXAMPLE 55, COMPOUND 59

[0677] N-(quinoline-8-carbonyl)-O-(trans-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl) homoserine. Prepared according to General Scheme A using General Procedure I with quinoline-8-carboxylic acid. LCMS theoretical m/z = 489.2. [M+H]+, found 489.3. EXAMPLE 56, COMPOUND 60

[0678] N-(3-cyclopropylbenzoyl)-O-(trans-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine. Prepared according to General Scheme A using General Procedure I with 3-cyclopropylbenzoic acid. LCMS theoretical m/z = 478.3. [M+H]+, found 478.3. EXAMPLE 57, COMPOUND 61

[0679] N-(4-cyclopropylbenzoyl)-O-(trans-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine. Prepared according to General Scheme A using General Procedure I with 4-cyclopropylbenzoic acid. LCMS theoretical m/z = 478.3. [M+H]+, found 478.3. EXAMPLE 58, COMPOUND 44

[0680] N-isonicotinoyl-O-(trans-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)-D-homoserine. The D1 isomer was used in General Scheme D-2 using General Procedure I with isonicotinic acid. LCMS theoretical m/z = 439.2. [M+H]+, found 439.3. EXAMPLE 59, COMPOUND 51

[0681] N-(3-ethylpentanoyl)-O-(trans-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)-D -homoserine. The D1 isomer was used in General Scheme D-2 using General Procedure I with 3-ethylpentanoic acid. LCMS theoretical m/z = 446.3. [M+H]+, found 446.3. EXAMPLE 60, COMPOUND 14 F

[0682] N-(2-chloro-3-fluorobenzoyl)-O-(trans-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl) cyclobutyl)homoserine. The D1 isomer was used in General Scheme D-2 using General Procedure I with 2-chloro-3-fluorobenzoic acid. LCMS theoretical m/z = 490.2. [M+H]+, found 490.2. EXAMPLE 61, COMPOUND 53

[0683] O-(trans-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)-N-(3-(thiazol-5 -yl)benzoyl)homoserine. The D1 isomer was used in General Scheme D-2 using General Procedure I with 3-(thiazol-5-yl)benzoic acid. LCMS theoretical m/z = 521.2. [M+H]+, found 521.2. EXAMPLE 62, COMPOUND 44

[0684] N-isonicotinoyl-O-(trans-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine. The D2 isomer was used in General Scheme D-2 using General Procedure I with isonicotinic acid. LCMS theoretical m/z = 439.2. [M+H]+, found 439.3. EXAMPLE 63, COMPOUND 51

[0685] N-(3-ethylpentanoyl)-O-(trans-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine. The D2 isomer was used in General Scheme D-2 using General Procedure I with 3-ethylpentanoic acid. LCMS theoretical m/z = 446.3. [M+H]+, found 446.3. EXAMPLE 64, COMPOUND 14

[0686] N-(2-chloro-3-fluorobenzoyl)-O-(trans-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl) cyclobutyl)homoserine. The D2 isomer was used in General Scheme D-2 using General Procedure I with 2-chloro-3-fluorobenzoic acid. LCMS theoretical m/z = 490.2. [M+H]+, found 490.2. EXAMPLE 65, COMPOUND 53

[0687] O-(trans-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)-N-(3-(thiazol-5 -yl)benzoyl)homoserine. The D2 isomer was used in General Scheme D-2 using General Procedure I with 3-(thiazol-5-yl)benzoic acid. LCMS theoretical m/z = 521.2. [M+H]+, found 521.2. EXAMPLE 66, COMPOUND 36

[0688] N-(3,4-difluorobenzoyl)-O-(cis-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl) homoserine. Prepared according to General Scheme B using General Procedure I with 3,4-difluorobenzoic acid. LCMS theoretical m/z = 474.2. [M+H]+, found 474.2. EXAMPLE 67, COMPOUND 51

[0689] N-(3-ethylpentanoyl)-O-(cis-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine. Prepared according to General Scheme B using General Procedure I with 3-ethylpentanoic acid. LCMS theoretical m/z = 446.3. [M+H]+, found 446.3. EXAMPLE 68, COMPOUND 44

[0690] N-isonicotinoyl-O-(cis-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine. Prepared according to General Scheme B using General Procedure I with isonicotinic acid. LCMS theoretical m/z = 439.2. [M+H]+, found 439.2. EXAMPLE 69, COMPOUND 53

[0691] O-(cis-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)-N-(3-(thiazol-5 -yl)benzoyl)homoserine. Prepared according to General Scheme B using General Procedure I with 3-(thiazol-5-yl)benzoic acid. LCMS theoretical m/z = 521.2. [M+H]+, found 521.2. EXAMPLE 70, COMPOUND 49

[0692] N-((R)-3-hydroxy-2-phenylquinolinayl)-O-(cis-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2- yl)ethyl)cyclobutyl)homoserine. Prepared according to General Scheme B using General Procedure I with (R)-3-hydroxy-2-phenylpropanoic acid and General Procedure N to provide the title compound as the first eluting isomer. LCMS theoretical m/z = 482.3. [M+H]+, found 482.3. EXAMPLE 71, COMPOUND 49

[0693] N-((R)-3-hydroxy-2-phenylquinolinayl)-O-(cis-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2- yl)ethyl)cyclobutyl)homoserine. Prepared according to General Scheme B using General Procedure I with (R)-3-hydroxy-2-phenylpropanoic acid, and General Procedure N to obtain the title compound as the second elution isomer. LCMS theoretical m/z = 482.3. [M+H]+, found 482.3. EXAMPLE 72, COMPOUND 62

[0694] N-(3-(1-methyl-1H-pyrazol-4-yl)benzoyl)-O-(trans-3-(4-(5,6,7,8-tetrahydro-1,8 -naphthyridin-2-yl)butyl)cyclobutyl)homoserine. Prepared according to General Scheme A using General Procedure I with 3-(1-methyl-1H-pyrazol-4-yl)benzoic acid. LCMS theoretical m/z = 518.2. [M+H]+, found 518.2. EXAMPLE 73, COMPOUND 63

[0695] N-(3-(1-methyl-1H-pyrazol-4-yl)benzoyl)-O-(4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2- il)butyl)homoserine. Prepared according to General Scheme C using General Procedure I with 3-(1-methyl-1H-pyrazol-4-yl)benzoic acid. LCMS theoretical m/z = 492.3. [M+H]+, found 492.3. EXAMPLE 74, COMPOUND 64

[0696] N-((S)-2-hydroxy-2-phenylacetyl)-O-(4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl)homoserine . Prepared according to General Scheme C using General Procedure I with (S)-2-hydroxy-2-phenylacetic acid and General Procedure N to provide the title compound as the first eluting isomer. LCMS theoretical m/z = 442.2. [M+H]+, found 442.2. EXAMPLE 75, COMPOUND 64

[0697] N-((S)-2-hydroxy-2-phenylacetyl)-O-(4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl)homoserine . Prepared according to General Scheme C using General Procedure I with (S)-2-hydroxy-2-phenylacetic acid, and General Procedure N to provide the title compound as the second elution isomer. LCMS theoretical m/z = 442.2. [M+H]+, found 442.2. EXAMPLE 76, COMPOUND 64

[0698] N-((R)-2-hydroxy-2-phenylacetyl)-O-(4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl)homoserine . Prepared according to General Scheme C using General Procedure I with (R)-2-hydroxy-2-phenylacetic acid, and General Procedure N to provide the title compound as the first eluting isomer. LCMS theoretical m/z = 442.2. [M+H]+, found 442.2. EXAMPLE 77, COMPOUND 64 cr OH

[0699] N-((R)-2-hydroxy-2-phenylacetyl)-O-(4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl)- D-homoserine. Prepared according to General Scheme C using General Procedure I with (R)-2-hydroxy-2-phenylacetic acid, and General Procedure N to provide the title compound as the second elution isomer. LCMS theoretical m/z = 442.2. [M+H]+, found 442.2. EXAMPLE 78, COMPOUND 65 O'OH

[0700] N-((S)-2-hydroxy-2-phenylacetyl)-O-(trans-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2- yl)ethyl)cyclobutyl)homoserine. Prepared according to General Scheme A using General Procedure I with (S)-2-hydroxy-2-phenylacetic acid and General Procedure N to provide the title compound as the first eluting isomer. LCMS theoretical m/z = 468.3. [M+H]+, found 468.3. EXAMPLE 79, COMPOUND 65 O'OH

[0701] N-((S)-2-hydroxy-2-phenylacetyl)-O-(trans-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2- yl)ethyl)cyclobutyl)homoserine. Prepared according to General Scheme A using General Procedure I with (S)-2-hydroxy-2-phenylacetic acid and General Procedure N to provide the title compound as the second elution isomer. LCMS theoretical m/z = 468.3. [M+H]+, found 468.3. EXAMPLE 80, COMPOUND 65

[0702] N-((R)-2-hydroxy-2-phenylacetyl)-O-(trans-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2- yl)ethyl)cyclobutyl)homoserine. Prepared according to General Scheme A using General Procedure I with (R)-2-hydroxy-2-phenylacetic acid, and General Procedure N to provide the title compound as the first eluting isomer. LCMS theoretical m/z = 468.3. [M+H]+, found 468.3. EXAMPLE 81, COMPOUND 65

[0703] N-((R)-2-hydroxy-2-phenylacetyl)-O-(trans-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2- yl)ethyl)cyclobutyl)homoserine. Prepared according to General Scheme A using General Procedure I with (R)-2-hydroxy-2-phenylacetic acid, and General Procedure N to provide the title compound as the second elution isomer. LCMS theoretical m/z = 468.3. [M+H]+, found 468.3. EXAMPLE 82, COMPOUND 66

[0704] N-(1-phenylcyclopropane-1-carbonyl)-O-(trans-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl) cyclobutyl)homoserine. The G1 isomer was used in General Scheme G-2 using General Procedure I with 1-phenylcyclopropane-1-carboxylic acid. LCMS theoretical m/z = 478.3. [M+H]+, found 478.3. EXAMPLE 83, COMPOUND 67

[0705] N-(2-methyl-2-phenylquinolinayl)-O-(trans-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl) cyclobutyl)homoserine. The G1 isomer was used in General Scheme G-2 using General Procedure I with 2-methyl-2-phenylpropanoic acid. LCMS theoretical m/z = 480.3. [M+H]+, found 480.1. EXAMPLE 84, COMPOUND 68

[0706] N-(1-phenylcyclobutane-1-carbonyl)-O-(trans-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl) cyclobutyl)homoserine The G1 isomer was used in General Scheme G-2 using General Procedure I with 1-phenylcyclobutane-1-carboxylic acid. LCMS theoretical m/z = 492.3. [M+H]+, found 492.2. EXAMPLE 85, COMPOUND 69

[0707] N-(2,2-dimethyl-3-phenylquinolinayl)-O-(trans-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl) ethyl)cyclobutyl)homoserine. The G1 isomer was used in General Scheme G-2 using General Procedure I with 2,2-dimethyl-3-phenylpropanoic acid. LCMS theoretical m/z = 494.3. [M+H]+, found 494.2. EXAMPLE 86, COMPOUND 19

[0708] N-(tert-butoxycarbonyl)-O-(trans-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine. Prepared using Scheme G-1 to produce Isomer G1, then using di-tert-butyl dicarbonate and triethylamine in DCM produced N-(tert-butoxycarbonyl)- O-(trans-3-(2-(5,6, 7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)methyl homoserinate, which was subjected to General Procedure No. Theoretical LCMS m/z = 434.3. [M+H]+, found 434.3. EXAMPLE 87, COMPOUND 70

[0709] N-(2-(4-fluorophenyl)-2-methylquinolinayl)-O-(trans-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2- yl)ethyl)cyclobutyl)homoserine. The G1 isomer was used in General Scheme G-2 using General Procedure I with 2-(4-fluorophenyl)-2-methylpropanoic acid. LCMS theoretical m/z = 498.3. [M+H]+, found 498.3. EXAMPLE 88, COMPOUND 71

[0710] N-(3-methylaxethane-3-carbonyl)-O-(trans-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl) cyclobutyl)homoserine. The G1 isomer was used in General Scheme G-2 using General Procedure I with 3-methylaxethane-3-carboxylic acid. LCMS theoretical m/z = 432.2. [M+H]+, found 432.2. EXAMPLE 89, COMPOUND 72

[0711] N-(3-hydroxy-2,2-dimethylquinolinayl)-O-(trans-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl) ethyl)cyclobutyl)homoserine. The G1 isomer was used in General Scheme G-2 using General Procedure I with 3-hydroxy-2,2-dimethylpropanoic acid. LCMS theoretical m/z = 434.3. [M+H]+, found 434.2. EXAMPLE 90, COMPOUND 73

[0712] N-(3-methoxy-2,2-dimethylquinolinayl)-O-(trans-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl) ethyl)cyclobutyl)homoserine. The G1 isomer was used in General Scheme G-2 using General Procedure I with 3-methoxy-2,2-dimethylpropanoic acid. LCMS theoretical m/z = 448.3. [M+H]+, found 448.3. EXAMPLE 91, COMPOUND 74

[0713] N-(2-methyl-2-(pyridin-3-yl)quinolinayl)-O-(trans-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin -2-yl)ethyl)cyclobutyl)homoserine. The G1 isomer was used in General Scheme G-2 using General Procedure I with 2-methyl-2-(pyridin-3-yl)propanoic acid. LCMS theoretical m/z = 481.3. [M+H]+, found 481.3. EXAMPLE 92, COMPOUND 75

[0714] N-(2,3-dihydro-1H-indene-2-carbonyl)-O-(trans-3-(2- (5,6,7,8-tetrahydro-1,8- naphthyridin-2-yl)ethyl)cyclobutyl)homoserine. The G1 isomer was used in General Scheme G-2 using General Procedure I with 2,3-dihydro-1H-indene-2-carboxylic acid. LCMS theoretical m/z = 478.3. [M+H]+, found 478.1. EXAMPLE 93, COMPOUND 76

[0715] N-(3-cyano-2,2-dimethylquinolinayl)-O-(trans-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl) ethyl)cyclobutyl)homoserine. The G1 isomer was used in General Scheme G-2 using General Procedure I with 3-cyano-2,2-dimethylpropanoic acid. LCMS theoretical m/z = 443.3. [M+H]+, found 443.1. EXAMPLE 94, COMPOUND 77

[0716] N-pivaloyl-O-(trans-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine. The G1 isomer was used in General Scheme G-2 using General Procedure I with pivalic acid. LCMS theoretical m/z = 418.3. [M+H]+, found 418.4. EXAMPLE 95, COMPOUND 78

[0717] N-(2,3-dihydro-1H-indene-1-carbonyl)-O-(trans-3-(2- (5,6,7,8-tetrahydro-1,8- naphthyridin-2-yl)ethyl)cyclobutyl)homoserine. The G1 isomer was used in General Scheme G-2 using General Procedure I with 2,3-dihydro-1H-indene-1-carboxylic acid and General Procedure N followed by separation of the diastereomers by chiral SFC to generate the compound of the title as the first eluting isomer as a single enantiomer. LCMS theoretical m/z = 478.3. [M+H]+, found 478.2. EXAMPLE 96, COMPOUND 78

[0718] N-(2,3-dihydro-1H-indene-1-carbonyl)-O-(trans-3-(2- (5,6,7,8-tetrahydro-1,8- naphthyridin-2-yl)ethyl)cyclobutyl)homoserine. The G1 isomer was used in General Scheme G-2 using General Procedure I with 2,3-dihydro-1H-indene-1-carboxylic acid and General Procedure N followed by separation of the diastereomers by chiral SFC to generate the compound of the title as the second elution isomer as a single enantiomer. LCMS theoretical m/z = 478.3. [M+H]+, found 478.2. EXAMPLE 97, COMPOUND 66

[0719] N-(1-phenylcyclopropane-1-carbonyl)-O-(trans-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl) cyclobutyl)homoserine. The D2 isomer was used in General Scheme D-2 using General Procedure I with 1-phenylcyclopropane-1-carboxylic acid. LCMS theoretical m/z = 478.3. [M+H]+, found 478.3. EXAMPLE 98, COMPOUND 67

[0720] N-(2-methyl-2-phenylquinolinayl)-O-(trans-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl) cyclobutyl)homoserine. The D2 isomer was used in General Scheme D-2 using General Procedure I with 2-methyl-2-phenylpropanoic acid. LCMS theoretical m/z = 480.3. [M+H]+, found 480.3. EXAMPLE 99, COMPOUND 68r

[0721] N-(1-phenylcyclobutane-1-carbonyl)-O-(trans-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl) cyclobutyl)homoserine. The D2 isomer was used in General Scheme D-2 using General Procedure I with 1-phenylcyclobutane-1-carboxylic acid. LCMS theoretical m/z = 492.3. [M+H]+, found 492.3. EXAMPLE 100, COMPOUND 69 HO

[0722] N-(2,2-dimethyl-3-phenylquinolinayl)-O-(trans-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl) ethyl)cyclobutyl)homoserine. The D2 isomer was used in General Scheme D-2 using General Procedure I with 2,2-dimethyl-3-phenylpropanoic acid. LCMS theoretical m/z = 494.3. [M+H]+, found 494.4. EXAMPLE 101, COMPOUND 19 HO O

[0723] N-(tert-butoxycarbonyl)-O-(trans-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine. The D2 isomer was used in General Procedure N. Theoretical LCMS m/z = 434.3. [M+H]+, found 434.2. EXAMPLE 102, COMPOUND 70 HO O

[0724] N-(2-(4-fluorophenyl)-2-methylquinolinayl)-O-(trans-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2- yl)ethyl)cyclobutyl)homoserine. The D2 isomer was used in General Scheme D-2 using General Procedure I with 2-(4-fluorophenyl)-2-methylpropanoic acid. LCMS theoretical m/z = 498.3. [M+H]+, found 498.3. EXAMPLE 103, COMPOUND 71

[0725] N-(3-methylaxethane-3-carbonyl)-O-(trans-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl) cyclobutyl)homoserine. The D2 isomer was used in General Scheme D-2 using General Procedure I with 3-methylaxethane-3-carboxylic acid. LCMS theoretical m/z = 432.2. [M+H]+, found 432.2. EXAMPLE 104, COMPOUND 72

[0726] N-(3-hydroxy-2,2-dimethylquinolinayl)-O-(trans-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl) ethyl)cyclobutyl)homoserine. The D2 isomer was used in General Scheme D-2 using General Procedure I with 3-hydroxy-2,2-dimethylpropanoic acid. LCMS theoretical m/z = 434.3. [M+H]+, found 434.4. EXAMPLE 105, COMPOUND 73

[0727] N-(3-methoxy-2,2-dimethylquinolinayl)-O-(trans-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl) ethyl)cyclobutyl)homoserine. The D2 isomer was used in General Scheme D-2 using General Procedure I with 3-methoxy-2,2-dimethylpropanoic acid. LCMS theoretical m/z = 448.3. [M+H]+, found 448.4. EXAMPLE 106, COMPOUND 74

[0728] N-(2-methyl-2-(pyridin-3-yl)quinolinayl)-O-(trans-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin -2-yl)ethyl)cyclobutyl)homoserine. The D2 isomer was used in General Scheme D-2 using General Procedure I with 2-methyl-2-(pyridin-3-yl)propanoic acid. LCMS theoretical m/z = 481.3. [M+H]+, found 481.4. EXAMPLE 107, COMPOUND 75

[0729] N-(2,3-dihydro-1H-indene-2-carbonyl)-O-(trans-3-(2- (5,6,7,8-tetrahydro-1,8- naphthyridin-2-yl)ethyl)cyclobutyl)homoserine. The D2 isomer was used in General Scheme D-2 using General Procedure I with 2,3-dihydro-1H-indene-2-carboxylic acid. LCMS theoretical m/z = 478.3. [M+H]+, found 478.4. EXAMPLE 108, COMPOUND 76

[0730] N-(3-cyano-2,2-dimethylquinolinayl)-O-(trans-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl) ethyl)cyclobutyl)homoserine. The D2 isomer was used in General Scheme D-2 using General Procedure I with 3-cyano-2,2-dimethylpropanoic acid. LCMS theoretical m/z = 443.3. [M+H]+, found 443.3. EXAMPLE 109, COMPOUND 77

[0731] N-pivaloyl-O-(trans-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine. Prepared using General Scheme D-2 starting with Isomer D2 using General Procedure I with pivalic acid. LCMS theoretical m/z = 418.3. [M+H]+, found 418.3. EXAMPLE 110, COMPOUND 78

[0732] N-(2,3-dihydro-1H-indene-1-carbonyl)-O-(trans-3-(2-(5,6,7,8-tetrahydro-1,8- naphthyridin-2-yl)ethyl)cyclobutyl)homoserine. The D2 isomer was used in General Scheme D-2 using General Procedure I with 2,3-dihydro-1H-indene-1-carboxylic acid and General Procedure N to obtain the title compound as the first isomer. elution as a single enantiomer. LCMS theoretical m/z = 478.3. [M+H]+, found 478.3. EXAMPLE 111, COMPOUND 78

[0733] N-(2,3-dihydro-1H-indene-1-carbonyl)-O-(trans-3-(2-(5,6,7,8-tetrahydro-1,8- naphthyridin-2-yl)ethyl)cyclobutyl)homoserine. The D2 isomer was used in General Scheme D-2 using General Procedure I with 2,3-dihydro-1H-indene-1-carboxylic acid and General Procedure N to obtain the title compound as the second isomer. elution as a single enantiomer. LCMS theoretical m/z = 478.3. [M+H]+, found 478.2. EXAMPLE 112, COMPOUND 79

[0734] N-((neopentyloxy)carbonyl)-O-(trans-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine . The D2 isomer was used in General Scheme D-2 using General Procedure F with neopentyl chloroformate. LCMS theoretical m/z = 448.3. [M+H]+, found 448.3. EXAMPLE 113, COMPOUND 80

[0735] N-((1-methylcyclopropoxy)carbonyl)-O-(trans-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl )homoserine. The D2 isomer was used in General Scheme D-2 using General Procedure J with 1-methylcyclopropan-1-ol, General Procedure K, and General Procedure N. Theoretical LCMS m/z = 432.3. [M+H]+, found 432.2. EXAMPLE 114, COMPOUND 81

[0736] N-((1-methylcyclobutoxy)carbonyl)-O-(trans-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl )homoserine. The D2 isomer was used in General Scheme D-2 using General Procedure J with 1-methylcyclobutan-1-ol, General Procedure K, and General Procedure N. Theoretical LCMS m/z = 446.3. [M+H]+, found 446.3. EXAMPLE 115, COMPOUND 82

[0737] O-(trans-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)-N-(((1,1, 1-trifluoro-2-methylpropan-2-yl)oxy)carbonyl)homoserine. The D2 isomer was used in General Scheme D-2 using General Procedure J with 1,1,1-trifluoro-2-methylpropan-2-ol, General Procedure K, and General Procedure N. Theoretical LCMS m/z = 488 ,two. [M+H]+, found 488.2. EXAMPLE 116, COMPOUND 83

[0738] N-(isopropoxycarbonyl)-O-(trans-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine. The D2 isomer was used in General Scheme D-2 using General Procedure F with isopropyl chloroformate. LCMS theoretical m/z = 420.3. [M+H]+, found 420.2. EXAMPLE 117, COMPOUND 84

[0739] N-(diethylcarbamoyl)-O-(trans-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine. The D2 isomer was used in General Scheme D-2 using General Procedure H with diethylcarbamoyl chloride. LCMS theoretical m/z = 433.3. [M+H]+, found 433.3. EXAMPLE 118, COMPOUND 85 HN^O HO O

[0740] N-(tert-butylcarbamoyl)-O-(trans-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine. The D2 isomer was sequentially used in General Procedure D, General Procedure G with tert-butylamine, and General Procedure N. Theoretical LCMS m/z = 433.3. [M+H]+, found 433.3. EXAMPLE 119, COMPOUND 86 l\L .O

[0741] N-(tert-butyl(methyl)carbamoyl)-O-(trans-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl) cyclobutyl)homoserine. The D2 isomer was sequentially used in General Procedure D, General Procedure G with N,2-dimethylpropan-2-amine, and General Procedure N. Theoretical LCMS m/z = 447.3. [M+H]+, found 447.3. EXAMPLE 120, COMPOUND 87 ISk .OH ISk ,N HO

[0742] N-(isopropyl(methyl)carbamoyl)-O-(trans-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl) homoserine. The D2 isomer was sequentially used in General Procedure D, General Procedure G with N-methylpropan-2-amine, and General Procedure N. Theoretical LCMS m/z = 433.3. [M+H]+, found 433.3. EXAMPLE 121, COMPOUND 88

[0743] N-(diisopropylcarbamoyl)-O-(trans-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine. The D2 isomer was sequentially used in General Procedure D, General Procedure G with diisopropylamine, and General Procedure N. Theoretical LCMS m/z = 461.3. [M+H]+, found 461.3. EXAMPLE 122, COMPOUND 89

[0744] N-(3,3-dimethylbutanoyl)-O-(trans-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl) homoserine. The D2 isomer was used in General Scheme D-2 using General Procedure I with 3,3-dimethylbutanoic acid. LCMS theoretical m/z = 432.3. [M+H]+, found 432.3. EXAMPLE 123, COMPOUND 90

[0745] N-(3-methylbutanoyl)-O-(trans-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine. The D2 isomer was used in General Scheme D-2 using General Procedure I with 3-methylbutanoic acid. LCMS theoretical m/z = 418.3. [M+H]+, found 418.3. EXAMPLE 124, COMPOUND 91

[0746] N-(2-cyclobutylacetyl)-O-(trans-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine. The D2 isomer was used in General Scheme D-2 using General Procedure I with 2-cyclobutylacetic acid. LCMS theoretical m/z = 430.3. [M+H]+, found 430.3. EXAMPLE 125, COMPOUND 92

[0747] N-(2-(1-methylcyclopropyl)acetyl)-O-(trans-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl )cyclobutyl)homoserine. The D2 isomer was used in General Scheme D-2 using General Procedure I with 2-(1-methylcyclopropyl)acetic acid. LCMS theoretical m/z = 430.3. [M+H]+, found 430.3. EXAMPLE 126, COMPOUND 93

[0748] N-(2-cyclopropylacetyl)-O-(trans-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine. The D2 isomer was used in General Scheme D-2 using General Procedure I with 2-cyclopropylacetic acid. LCMS theoretical m/z = 416.3. [M+H]+, found 416.3. EXAMPLE 127, COMPOUND 94

[0749] N-(((1-(tert-butoxycarbonyl)-3-methylazetidin-3-yl)oxy)carbonyl)-O-(trans-3-(2-(5,6,7,8-tetra- hydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine. The D2 isomer was used sequentially in General Procedure D, in General Procedure K with tert-butyl 3-((((2,5-dioxopyrrolidin-1-yl)oxy)carbonyl)oxy)-3-methylazetidine-1-carboxylate (prepared using General Procedure J with tert-butyl 3-hydroxy-3-methylazetidine-1-carboxylate) and General Procedure N. Theoretical LCMS m/z = 547.31. [M+H]+, found 547.3. EXAMPLE 128, COMPOUND 95

[0750] N-(((3-methyl-1-(methylsulfonyl)azetidin-3-yl)oxy)carbonyl)-O- (trans-3-(2-(5,6,7,8-tetrahydro -1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine. The D2 isomer was sequentially used in General Procedure D, in General Procedure K with tert-butyl 3-((((2,5-dioxopyrrolidin-1-yl)oxy)carbonyl)oxy)-3-methylazetidine-1-carboxylate (prepared using General Procedure J with tert-butyl 3-hydroxy-3-methylazetidine-1-carboxylate), in General Procedure D, in General Procedure M, then in General Procedure N. Theoretical LCMS m/z = 525.24. [M+H]+, found 525.2. EXAMPLE 129, COMPOUND 96

[0751] N-(((1-acetyl-3-methylazetidin-3-yl)oxy)carbonyl)-O-(trans-3- (2-(5,6,7,8-tetrahydro-1, 8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine. The D2 isomer was sequentially used in General Procedure D, in General Procedure K with tert-butyl 3-((((2,5-dioxopyrrolidin-1-yl)oxy)carbonyl)oxy)-3-methylazetidine-1-carboxylate (prepared using General Procedure J with tert-butyl 3-hydroxy-3-methylazetidine-1-carboxylate), in General Procedure D, in General Procedure L, then in General Procedure N. Theoretical LCMS m/z = 489.27. [M+H]+, found 489.3. EXAMPLE 130, COMPOUND 97

[0752] N-(((3-methylazetidin-3-yl)oxy)carbonyl)-O-(trans-3-(2- (5,6,7,8-tetrahydro-1,8-naphthyridin- 2-yl)ethyl)cyclobutyl)homoserine. The D2 isomer was sequentially used in General Procedure D, in General Procedure K with tert-butyl 3-((((2,5-dioxopyrrolidin-1-yl)oxy)carbonyl)oxy)-3-methylazetidine-1-carboxylate (prepared using General Procedure J with tert-butyl 3-hydroxy-3-methylazetidine-1-carboxylate), in General Procedure D, then in General Procedure N. Theoretical LCMS m/z = 447.26. [M+H]+, found 447.3. EXAMPLE 131, COMPOUND 98

[0753] N-((cyclohexyloxy)carbonyl)-O-(trans-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl )homoserine. The D2 isomer was used in General Scheme D-2 using General Procedure F with cyclohexyl chloroformate. LCMS theoretical m/z = 460.28. [M+H]+, found 460.3. EXAMPLE 132, COMPOUND 99

[0754] N-(isobutoxycarbonyl)-O-(trans-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine. The D2 isomer was used in General Scheme D-2 using General Procedure F with isobutyl chloroformate. LCMS theoretical m/z = 434.27. [M+H]+, found 434.3. EXAMPLE 133, COMPOUND 100

[0755] N-((((S)-1-(tert-butoxycarbonyl)pyrrolidin-3-yl)oxy)carbonyl)-O-(trans-3-(2-(5,6,7,8-tetra -hydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine. The D2 isomer was sequentially used in General Procedure D, in General Procedure K with (S)-3- ((((2,5-dioxopyrrolidin-1-yl)oxy)carbonyl)oxy)tert-pyrrolidine-1-carboxylate butyl (prepared using General Procedure J with tert-butyl (S)-3-hydroxypyrrolidine-1-carboxylate), then the in General Procedure N. LCMS theoretical m/z = 547.31. [M+H]+, found 547.3. EXAMPLE 134, COMPOUND 101

[0756] N-((((S)-pyrrolidin-3-yl)oxy)carbonyl)-O-(trans-3-(2-(5,6,7,8-tetrahydro-1,8- naphthyridin-2-yl)ethyl)cyclobutyl)homoserine. The D2 isomer was sequentially used in General Procedure D, in General Procedure K with (S)-3-((((2,5-dioxopyrrolidin-1-yl)oxy)carbonyl)oxy)tert-pyrrolidine-1-carboxylate butyl (prepared using General Procedure J with (S)-3-hydroxypyrrolidine-1-tert-butyl carboxylate), in General Procedure D, then in General Procedure N. Theoretical LCMS m/z = 447.26. [M+H]+, found 447.3. EXAMPLE 135, COMPOUND 102

[0757] N-(4-(methylsulfonyl)butanoyl)-O-(trans-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl )homoserine. The D2 isomer was used in General Scheme D-2 using General Procedure I with 4-(methylsulfonyl)butanoic acid. LCMS theoretical m/z = 482.23. [M+H]+, found 482.2. EXAMPLE 136, COMPOUND 103

[0758] N-((((S)-1-(methylsulfonyl)pyrrolidin-3-yl)oxy)carbonyl)-O- (trans-3-(2-(5,6,7,8-tetrahydro -1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine. The D2 isomer was sequentially used in General Procedure D, in General Procedure K with (S)-3- ((((2,5-dioxopyrrolidin-1-yl)oxy)carbonyl)oxy)tert-pyrrolidine-1-carboxylate butyl (prepared using General Procedure J with tert-butyl (S)-3-hydroxypyrrolidine-1-carboxylate), in General Procedure D, in General Procedure M, then in General Procedure N. Theoretical LCMS m/z = 525, 24. [M+H]+, found 525.2. EXAMPLE 137, COMPOUND 104

[0759] N-((((S)-1-acetylpyrrolidin-3-yl)oxy)carbonyl)-O-(trans-3-(2- (5,6,7,8-tetrahydro-1, 8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine. The D2 isomer was sequentially used in General Procedure D, in General Procedure K with (S)-3-((((2,5-dioxopyrrolidin-1-yl)oxy)carbonyl)oxy)tert-pyrrolidine-1-carboxylate butyl (prepared using General Procedure J with (S)-3-hydroxypyrrolidine-1-tert-butyl carboxylate), in General Procedure D, in General Procedure L, then in General Procedure N. Theoretical LCMS m/z = 489, 27. [M+H]+, found 489.3. EXAMPLE 138, COMPOUND 100

[0760] N-((((R)-1-(tert-butoxycarbonyl)pyrrolidin-3-yl)oxy)carbonyl)-O-(trans-3-(2-(5,6,7,8-tetra -hydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine. The D2 isomer was sequentially used in General Procedure D, in General Procedure K with (R)-3- ((((2,5-dioxopyrrolidin-1-yl)oxy)carbonyl)oxy)tert-pyrrolidine-1-carboxylate butyl (prepared using General Procedure J with tert-butyl (R)-3-hydroxypyrrolidine-1-carboxylate), then in General Procedure N. LCMS theoretical m/z = 547.31. [M+H]+, found 547.3. EXAMPLE 139, COMPOUND 104

[0761] N-((((R)-1-acetylpyrrolidin-3-yl)oxy)carbonyl)-O-(trans-3-(2- (5,6,7,8-tetrahydro-1, 8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine. The D2 isomer was sequentially used in General Procedure D, in General Procedure K with (R)-3-((((2,5-dioxopyrrolidin-1-yl)oxy)carbonyl)oxy)tert-pyrrolidine-1-carboxylate butyl (prepared using General Procedure J with (R)-3-hydroxypyrrolidine-1-tert-butyl carboxylate), in General Procedure D, in General Procedure L, then in General Procedure N. Theoretical LCMS m/z = 489, 27. [M+H]+, found 489.3. EXAMPLE 140, COMPOUND 105

[0762] N-(((R)-1-phenylethoxy)carbonyl)-O-(trans-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl )ethyl)cyclobutyl)homoserine. The D2 isomer was used in General Scheme D-2 using General Procedure K with (R)-2,5-dioxopyrrolidin-1-yl (1-phenylethyl)carbonate (prepared using General Procedure J with (R)-1 -phenylethane-1-ol). LCMS theoretical m/z = 482.27. [M+H]+, found 482.3. EXAMPLE 141, COMPOUND 105

[0763] N-(((S)-1-phenylethoxy)carbonyl)-O-(trans-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl )ethyl)cyclobutyl)homoserine. The D2 isomer was used in General Scheme D-2 using General Procedure K with (S)-2,5-dioxopyrrolidin-1-yl (1-phenylethyl)carbonate (prepared using General Procedure J with (S)-1 -phenylethane-1-ol). LCMS theoretical m/z = 482.27. [M+H]+, found 482.3. EXAMPLE 142, COMPOUND 106

[0764] N-((2-phenylcyclobutoxy)carbonyl)-O-(trans-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl )homoserine. The D2 isomer was used in General Scheme D-2 using General Procedure K with 2,5-dioxopyrrolidin-1-yl (2-phenylcyclobutyl)carbonate (prepared using General Procedure J with 2-phenylcyclobutan-1-ol). LCMS theoretical m/z = 508.28. [M+H]+, found 508.3. EXAMPLE 143, COMPOUND 107

[0765] N-((cis-3-phenylcyclobutoxy)carbonyl)-O-(trans-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl )cyclobutyl)homoserine. The D2 isomer was used in General Scheme D-2 using General Procedure K with 2,5-dioxopyrrolidin-1-yl ((1s,3s)-3-phenylcyclobutyl)carbonate (prepared using General Procedure J with (1s, 3s)-3-phenylcyclobutan-1-ol). LCMS theoretical m/z = 508.28. [M+H]+, found 508.3. EXAMPLE 144, COMPOUND 108

[0766] N-((((1R,2S)-2-phenylcyclohexyl)oxy)carbonyl)-O-(trans-3-(2- (5,6,7,8-tetrahydro-1, 8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine. The D2 isomer was used in General Scheme D-2 using General Procedure K with 2,5-dioxopyrrolidin-1-yl ((1R,2S)-2-phenylcyclohexyl)carbonate (prepared using General Procedure J with ( 1R,2S)-2-phenylcyclohexan-1-ol). LCMS theoretical m/z = 536.31. [M+H]+, found 536.3. EXAMPLE 145, COMPOUND 109

[0767] Synthesis of trans-2-((tert-butoxycarbonyl)amino)-3-methyl-4-(trans-3-(2-(5,6,7,8-tetrahydro-1,8-) acid naphthyridin-2-yl)ethyl)cyclobutoxy)butanoic acid and cis-2-((tert-butoxycarbonyl)amino)-3-methyl-4-(trans-3-(2-(5,6,7,8-tetra) -hydro-1,8-naphthyridin-2-yl)ethyl)cyclobutoxy)butanoic acid (racemate)

[0768] 2-(2-((1r,3s)-3-((2-methylallyl)oxy)cyclobutyl)ethyl)-1,8-naphthyridine. To a suspension of sodium hydride (60 wt% dispersion in mineral oil, 64 mg, 1.59 mmol) in DMF (3 ml) at 0 °C was added (1s,3r)-3-(2-( 1,8-naphthyridin-2-yl)ethyl)cyclobutan-1-ol (302 mg, 1.32 mmol) in DMF (2 ml) and the resulting mixture was allowed to warm to room temperature and stirred for an additional 30 minutes. To this was then added 3-bromo-2-methylprop-1-ene (357 mg, 2.65 mmol) and the reaction mixture was stirred for 4 hours at room temperature and then diluted with saturated aqueous NaHCO3 solution and extracted with EtOAc. The combined organic extracts were dried over Na2SO4, filtered and concentrated in vacuo. The crude residue was purified by normal phase chromatography on silica gel to provide 2-(2-((1r,3s)-3-((2-methylallyl)oxy)cyclobutyl)ethyl)-1,8-naphthyridine. y-

[0769] 1-((1s,3r)-3-(2-(1,8-naphthyridin-2-yl)ethyl)cyclobutoxy)propan-2-one. To a mixture of 2-(2-((1r,3s)-3-((2-methylallyl)oxy)cyclobutyl)ethyl)-1,8-naphthyridine (174 mg, 0.62 mmol) in Dioxane/H2O at 3:1 (3 ml) was added 2,6-lutidine (132 mg, 1.23 mmol), NaIO4 (527 mg, 2.46 mmol), then K2OsO4^2H2O (11 mg, 0.03 mmol) and the The resulting mixture was allowed to stir at room temperature for 3 hours. The mixture was filtered and concentrated in vacuo. The crude residue was purified by normal phase chromatography on silica gel to provide 1-((1s,3r)- 3-(2-(1,8-naphthyridin-2-yl)ethyl)cyclobutoxy)propan-2- one.

[0770] 4-((1s,3r)-3-(2-(1,8-naphthyridin-2-yl)ethyl)cyclobutoxy)-2-((tert-butoxycarbonyl)amino)-3-methylbut-2- methyl enoate. To a solution of 1-((1s,3r)-3-(2-(1,8-naphthyridin-2-yl)ethyl)cyclobutoxy)propan-2-one (175 mg, 0.62 mmol) in CH2Cl2 ( 2 ml) methyl 2-((tert-butoxycarbonyl)amino)-2-(dimethoxyphosphoryl)acetate (366 mg, 1.23 mmol) was added, then 1,1,3,3-tetramethylguanidine (142 mg, 1 .23 mmol) and the resulting mixture was heated at 40 °C for 2 days. The reaction mixture was cooled to room temperature and then concentrated in vacuum. The crude residue was purified by normal phase chromatography on silica gel to give 4-((1s,3r)-3-(2-(1,8-naphthyridin-2-yl)ethyl)cyclobutoxy)-2-(( methyl tert-butoxycarbonyl)amino)-3-methylbut-2-enoate..

[0771] 2-((tert-butoxycarbonyl)amino)-3-methyl-4-((1s,3r)-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin Methyl -2-yl)ethyl)cyclobutoxy)butanoate. To a vial containing 4-((1s,3r)-3-(2-(1,8-naphthyridin-2-yl)ethyl)cyclobutoxy)-2-((tert-butoxycarbonyl)amino)-3-methylbut-2 -methyl enoate (148 mg, 0.32 mmol) was charged Pd(OH)2/C (20% by weight on carbon, 30 mg) and the mixture was evacuated and filled with H2 gas for 3 cycles and then , stirred under an H2 atmosphere overnight. The reaction mixture was filtered through a pad of Celite and rinsed with MeOH and then concentrated in vacuo. The crude residue was purified by normal phase chromatography on silica gel to give 2-((tert-butoxycarbonyl)amino)-3-methyl-4-((1s,3r)-3-(2-(5,6, 7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutoxy)methylbutanoate. EXAMPLE 145A, COMPOUND 109

[0772] 2-((tert-butoxycarbonyl)amino)-3-methyl-4-(trans-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-) acid yl)ethyl)cyclobutoxy)butanoic acid. Prepared starting with 2-((tert-butoxycarbonyl)amino)-3-methyl-4-(trans-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl )ethyl)cyclobutoxy)methylbutanoate, then using General Procedure N in which a racemic mixture of the title compound was isolated as the second eluting isomer by reverse phase preparative HPLC. LCMS theoretical m/z = 448.28. [M+H]+, found 448.3. The absolute stereochemistry of the product of Example 145a was subsequently designated as (2S,3S)-2-((tert-butoxycarbonyl)amino)-3-methyl-4-((1s,3S)-3-(2-(5) ,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutoxy)butanoic acid. EXAMPLE 145B, COMPOUND 109

[0773] 2-((tert-butoxycarbonyl)amino)-3-methyl-4-(trans-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-) acid yl)ethyl)cyclobutoxy)butanoic acid. Prepared starting with 2-((tert-butoxycarbonyl)amino)-3-methyl-4-(trans-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl )ethyl)cyclobutoxy)methylbutanoate, then using General Procedure N whereby a racemic mixture of the title compound was isolated as the first elution peak by reversed phase preparative HPLC. LCMS theoretical m/z = 448.28. [M+H]+, found 448.3. The absolute stereochemistry of the product of Example 145b was subsequently designated as (2S,3R)-2-((tert-butoxycarbonyl)amino)-3-methyl-4-((1s,3R)-3-(2-(5) ,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutoxy)butanoic acid (see structure in Figure 1, Table 2). EXAMPLE 146, COMPOUND 108

[0774] N-((((1S,2R)-2-phenylcyclohexyl)oxy)carbonyl)-O-(trans-3-(2- (5,6,7,8-tetrahydro-1, 8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine. The D2 isomer was used in General Scheme D-2 using General Procedure K with 2,5-dioxopyrrolidin-1-yl ((1S,2R)-2-phenylcyclohexyl)carbonate (prepared using General Procedure J with ( 1S,2R)-2-phenylcyclohexan-1-ol). LCMS theoretical m/z = 536.31. [M+H]+, found 536.3. EXAMPLE 147, COMPOUND 110

[0775] N-(((1-(tert-butoxycarbonyl)azetidin-3-yl)oxy)carbonyl)-O- (trans-3-(2-(5,6,7,8-tetrahydro-1 ,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine. The D2 isomer was sequentially used in General Procedure D, in General Procedure K with tert-butyl 3-((((2,5-dioxopyrrolidin-1-yl)oxy)carbonyl)oxy)azetidine-1-carboxylate (prepared using General Procedure J with tert-butyl 3-hydroxyazetidine-1-carboxylate), then General Procedure N. Theoretical LCMS m/z = 533.30. [M+H]+, found 533.3. EXAMPLE 148, COMPOUND 111

[0776] N-(((trans-4-phenylcyclohexyl)oxy)carbonyl)-O-(trans-3-(2- (5,6,7,8-tetrahydro-1,8-naphthyridin- 2-yl)ethyl)cyclobutyl)homoserine. The D2 isomer was used in General Scheme D-2 using General Procedure K with 2,5-dioxopyrrolidin-1-yl (trans-4-phenylcyclohexyl)carbonate (prepared using General Procedure J with trans-4-phenylcyclohexyl) - hexan-1-ol). LCMS theoretical m/z = 536.31. [M+H]+, found 536.3. EXAMPLE 149, COMPOUND 111

[0777] N-(((cis-4-phenylcyclohexyl)oxy)carbonyl)-O-(trans-3-(2- (5,6,7,8-tetrahydro-1,8-naphthyridin- 2-yl)ethyl)cyclobutyl)homoserine. The D2 isomer was used in General Scheme D-2 using General Procedure K with 2,5-dioxopyrrolidin-1-yl (cis-4-phenylcyclohexyl)carbonate (prepared using General Procedure J with cis-4-phenylcyclohexyl)carbonate. -hexan- 1-ol). LCMS theoretical m/z = 536.31. [M+H]+, found 536.3. EXAMPLE 150, COMPOUND 112

[0778] N-(((1-acetylazetidin-3-yl)oxy)carbonyl)-O-(trans-3-(2- (5,6,7,8-tetrahydro-1,8-naphthyridin- 2-yl)ethyl)cyclobutyl)homoserine. The D2 isomer was sequentially used in General Procedure D, in General Procedure K with tert-butyl 3-((((2,5-dioxopyrrolidin-1-yl)oxy)carbonyl)oxy)azetidine-1-carboxylate (prepared using General Procedure J with tert-butyl 3-hydroxyazetidine-1-carboxylate), General Procedure D, General Procedure L, then General Procedure N. Theoretical LCMS m/z = 475.26. [M+H]+, found 475.3. EXAMPLE 151, COMPOUND 113

[0779] N-((((S)-1-acetamidopropan-2-yl)oxy)carbonyl)-O-(trans-3- (2-(5,6,7,8-tetrahydro-1, 8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine. The D2 isomer was sequentially used in General Procedure D, in General Procedure K with tert-butyl (S)-(2-((((2,5-dioxopyrrolidin-1-yl)oxy)carbonyl)oxy)propyl)carbamate (prepared using General Procedure J with tert-butyl (S)-(2-hydroxypropyl)carbamate), in General Procedure D, in General Procedure L, then in General Procedure N. Theoretical LCMS m/z = 477.27. [M+H]+, found 477.3. EXAMPLE 152, COMPOUND 114

[0780] N-((((S)-1-((tert-butoxycarbonyl)amino)propan-2-yl)oxy)carbonyl)-O-(trans-3-(2-(5,6,7, 8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine. The D2 isomer was sequentially used in General Procedure D, in General Procedure K with tert-butyl (S)-(2- ((((2,5-dioxopyrrolidin-1-yl)oxy)carbonyl)oxy)propyl)carbamate (prepared using General Procedure J with tert-butyl (S)-(2-hydroxypropyl)carbamate), then in General Procedure N. LCMS theoretical m/z = 535.31. [M+H]+, found 535.3. EXAMPLE 153

[0781] N-((((R)-1-((tert-butoxycarbonyl)amino)propan-2-yl)oxy)carbonyl)-O-(trans-3-(2-(5,6,7, 8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine. The D2 isomer was sequentially used in General Procedure D, in General Procedure K with tert-butyl (R)-(2- ((((2,5-dioxopyrrolidin-1-yl)oxy)carbonyl)oxy)propyl)carbamate (prepared using General Procedure J with tert-butyl (R)-(2-hydroxypropyl)carbamate), then in General Procedure N. LCMS theoretical m/z = 535.31. [M+H]+, found 535.3. EXAMPLE 154, COMPOUND 113

[0782] N-((((R)-1-acetamidopropan-2-yl)oxy)carbonyl)-O-(trans-3- (2-(5,6,7,8-tetrahydro-1, 8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine. The D2 isomer was sequentially used in General Procedure D, in General Procedure K with tert-butyl (R)-(2-((((2,5-dioxopyrrolidin-1-yl)oxy)carbonyl)oxy)propyl)carbamate (prepared using General Procedure J with tert-butyl (R)-(2-hydroxypropyl)carbamate), in General Procedure D, in General Procedure L, then in General Procedure N. Theoretical LCMS m/z = 477.27. [M+H]+, found 447.3. EXAMPLE 155A, COMPOUND 115

[0783] N-((((trans)-2-(3,5-dimethyl-1H-pyrazol-1-yl)cyclopentyl)oxy)carbonyl)-O-(trans-3-(2-(5,6 ,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine. The D2 isomer was sequentially used in General Procedure D, in General Procedure K with trans-2-(3,5-dimethyl-1H-pyrazol-1-yl)cyclopentyl (2,5-dioxopyrrolidin-1-yl)carbonate ( racemic, prepared using General Procedure J with trans-2-(3,5-dimethyl-1H-pyrazol-1-yl)cyclopentan-1-ol), then in General Procedure N followed by preparative HPLC to obtain the compound of title as the first eluting isomer of unknown absolute stereochemistry in cyclopentane. LCMS theoretical m/z = 540.32. [M+H]+, found 540.3. The absolute stereochemistry of the product of Example 155a was subsequently assigned as N-((((1R,2R)-2-(3,5-dimethyl-1H-pyrazol-1-yl)cyclopentyl)oxy)carbonyl)-O-( (1s,3S)-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)-L-homoserine (see structure in Figure 1, Table two). EXAMPLE 155B, COMPOUND 115

[0784] N-((((trans)-2-(3,5-dimethyl-1H-pyrazol-1-yl)cyclopentyl)oxy)carbonyl)-O-(trans-3-(2-(5,6 ,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine. The D2 isomer was sequentially used in General Procedure D, in General Procedure K with trans-2-(3,5-dimethyl-1H-pyrazol-1-yl)cyclopentyl (2,5-dioxopyrrolidin-1-yl)carbonate ( racemic, prepared using General Procedure J with trans-2-(3,5-dimethyl-1H-pyrazol-1-yl)cyclopentan-1-ol), then in General Procedure N followed by preparative HPLC to obtain the compound of title as the second eluting isomer of unknown absolute stereochemistry in cyclopentane. LCMS theoretical m/z = 540.32. [M+H]+, found 540.3. The absolute stereochemistry of the product of Example 155b was subsequently assigned as N-((((1S,2S)-2-(3,5-dimethyl-1H-pyrazol-1-yl)cyclopentyl)oxy)carbonyl)-O-( (1s,3S)-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)-L-homoserine (see structure in Figure 1, Table two). EXAMPLE 156A, COMPOUND 116

[0785] N-((((trans)-2-(3,5-dimethyl-1H-pyrazol-1-yl)cyclohexyl)oxy)carbonyl)-O-(trans-3-(2-(5 ,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine. The D2 isomer was sequentially used in General Procedure D, in General Procedure K with trans-2-(3,5-dimethyl-1H-pyrazol-1-yl)cyclohexyl (2,5-dioxopyrrolidin-1-yl)carbonate (racemic, prepared using General Procedure J with trans-2-(3,5-dimethyl-1H-pyrazol-1-yl)cyclohexan-1-ol), then in General Procedure N followed by preparative HPLC to obtain the title compound as the first eluting isomer of unknown absolute stereochemistry in cyclohexane. LCMS theoretical m/z = 554.33. [M+H]+, found 554.4. The absolute stereochemistry of the product of Example 156a was subsequently assigned as N-((((1R,2R)-2-(3,5-dimethyl-1H-pyrazol-1-yl)cyclohexyl)oxy)carbonyl)-O -((1s,3S)-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)-L-homoserine (see structure in Figure 1 , Table 2). EXAMPLE 156B, COMPOUND 116

[0786] N-((((trans)-2-(3,5-dimethyl-1H-pyrazol-1-yl)cyclohexyl)oxy)carbonyl)-O-(trans-3-(2-(5 ,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine. The D2 isomer was sequentially used in General Procedure D, in General Procedure K with trans-2-(3,5-dimethyl-1H-pyrazol-1-yl)cyclo(2,5-dioxopyrrolidin-1-yl)carbonate. hexyl (racemic, prepared using General Procedure J with trans-2-(3,5-dimethyl-1H-pyrazol-1-yl)cyclohexan-1-ol), then in General Procedure N followed by preparative HPLC to determine obtain the title compound as the second elution isomer of unknown absolute stereochemistry in cyclohexane. LCMS theoretical m/z = 554.33. [M+H]+, found 554.4. The absolute stereochemistry of the product of Example 156b was subsequently assigned as N-((((1S,2S)-2-(3,5-dimethyl-1H-pyrazol-1-yl)cyclohexyl)oxy)carbonyl)-O - ((1s,3S)-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)-L-homoserine (see structure in Figure 1 , Table 2). EXAMPLE 157, COMPOUND 117 HO

[0787] N-(((1-(tert-butoxycarbonyl)-3-(3-chlorophenyl)azetidin-3-yl)oxy)carbonyl)-O-(trans-3-(2-(5,6,7 ,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine. The D2 isomer was sequentially used in General Procedure D, in General Procedure K with 3-(3-chlorophenyl)-3-((((2,5-dioxopyrrolidin-1-yl)oxy)carbonyl)oxy)azetidine-1- tert-butyl carboxylate (prepared using General Procedure J with tert-butyl 3-(3-chlorophenyl)-3-hydroxyazetidine-1-carboxylate), then in General Procedure N. Theoretical LCMS m/z = 643.29. [M+H]+, found 643.3. EXAMPLE 158, COMPOUND 118 HO O

[0788] N-(((1-(tert-butoxycarbonyl)-3-(4-isopropylphenyl)azetidin-3-yl)oxy)carbonyl)-O-(trans-3-(2-(5,6,7 ,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine. The D2 isomer was sequentially used in General Procedure D, in General Procedure K with 3- ((((2,5-dioxopyrrolidin-1-yl)oxy)carbonyl)oxy)-3-(4-isopropylphenyl)azetidine- 1- tert-butyl carboxylate (prepared using General Procedure J with tert-butyl 3-hydroxy-3-(4-isopropylphenyl)azetidine-1-carboxylate), then in General Procedure N. Theoretical LCMS m/z = 651.38 . [M+H]+, found 651.4. EXAMPLE 159, COMPOUND 119

[0789] N-(((1-(tert-butoxycarbonyl)-3-(phenylethynyl)azetidin-3-yl)oxy)carbonyl)-O-(trans-3-(2-(5,6,7,8 -tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine. The D2 isomer was sequentially used in General Procedure D, in General Procedure K with 3- ((((2,5-dioxopyrrolidin-1-yl)oxy)carbonyl)oxy)-3-(phenylethynyl)azetidine-1-carboxylate tert-butyl (prepared using General Procedure J with tert-butyl 3-hydroxy-3-(phenylethynyl)azetidine-1-carboxylate), then in General Procedure N. LCMS theoretical m/z = 633.33. [M+H]+, found 633.4. EXAMPLE 160, COMPOUND 120

[0790] N-(1-(tert-butoxycarbonyl)piperidine-4-carbonyl)-O-(trans-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2 - yl)ethyl)cyclobutyl)homoserine. The D2 isomer was used in General Scheme D-2 using General Procedure I with 1-(tert-butoxycarbonyl)piperidine-4-carboxylic acid. LCMS theoretical m/z = 545.33. [M+H]+, found 545.3. EXAMPLE 161, COMPOUND 121 O".

[0791] N-(3,3-difluorocyclohexane-1-carbonyl)-O-(trans-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2- yl)ethyl)cyclobutyl)homoserine. The D2 isomer was used in General Scheme D-2 using General Procedure I with 3,3-difluorocyclohexane-1-carboxylic acid. LCMS theoretical m/z = 480.27. [M+H]+, found 480.3. EXAMPLE 162A, COMPOUND 122

[0792] N-(-2-ethyl-4,4-difluorobutanoyl)-O-(trans-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl )ethyl)cyclobutyl)homoserine. The D2 isomer was used in General Scheme D-2 using General Procedure I with 2-ethyl-4,4-difluorobutanoic acid, then General Procedure N followed by preparative HPLC to obtain the title compound as the first eluting isomer. of unknown absolute stereochemistry in 2-ethyl-4,4-difluorobutanoic amide. LCMS theoretical m/z = 468.27. [M+H]+, found 468.3. The absolute stereochemistry of the product of Example 162a was subsequently assigned as N-((S)-2-ethyl-4,4-difluorobutanoyl)-O-((1s,3S)-3-(2-(5,6,7 ,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)-L-homoserine (see structure in Figure 1, Table 2). EXAMPLE 162B, COMPOUND 122

[0793] N-(-2-ethyl-4,4-difluorobutanoyl)-O-(trans-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl )ethyl)cyclobutyl)homoserine. The D2 isomer was used in General Scheme D-2 using General Procedure I with 2-ethyl-4,4-difluorobutanoic acid, then General Procedure N followed by preparative HPLC to obtain the title compound as the second eluting isomer. of unknown absolute stereochemistry in 2-ethyl-4,4-difluorobutanoic amide. LCMS theoretical m/z = 468.27. [M+H]+, found 468.3. The absolute stereochemistry of the product of Example 162a was subsequently assigned as N-((R)-2-ethyl-4,4-difluorobutanoyl)-O-((1s,3S)-3-(2-(5,6,7 ,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)-L-homoserine (see structure in Figure 1, Table 2). EXAMPLE 163A, COMPOUND 123

[0794] N-(((trans-2-(phenylethynyl)cyclohexyl)oxy)carbonyl)-O-(trans-3-(2-(5,6,7,8-tetrahydro-1,8 -naphthyridin-2- yl)ethyl)cyclobutyl)homoserine. The D2 isomer was sequentially used in General Procedure D, in General Procedure K with 2,5-dioxopyrrolidin-1-yl trans-2-(phenylethynyl)cyclohexyl)carbonate (prepared using General Procedure J with trans-2- (phenylethynyl)cyclohexan-1-ol) and in General Procedure N followed by preparative HPLC to obtain the title compound as the first eluting isomer of unknown absolute stereochemistry in cyclohexane. LCMS theoretical m/z = 560.31. [M+H]+, found 560.3. The absolute stereochemistry of the product of Example 163a was subsequently assigned as N-((((1R,2S)-2-(phenylethynyl)cyclohexyl)oxy)carbonyl)-O-((1s,3S)-3-(2 -(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)-L-homoserine (see structure in Figure 1, Table 2).

[0795] N-(((trans-2-(phenylethynyl)cyclohexyl)oxy)carbonyl)-O-(trans-3-(2-(5,6,7,8-tetrahydro-1,8 -naphthyridin-2- yl)ethyl)cyclobutyl)homoserine. The D2 isomer was sequentially used in General Procedure D, in General Procedure K with 2,5-dioxopyrrolidin-1-yl trans-2-(phenylethynyl)cyclohexyl)carbonate (prepared using General Procedure J with trans-2- (phenylethynyl)cyclohexan-1-ol), then in General Procedure N followed by preparative HPLC to produce the title compound as the second eluting isomer of unknown absolute stereochemistry in cyclohexane. LCMS theoretical m/z = 560.31. [M+H]+, found 560.3. The absolute stereochemistry of the product of Example 163b was subsequently assigned as N-((((1S,2R)-2-(phenylethynyl)cyclohexyl)oxy)carbonyl)-O-((1s,3S)-3-(2 -(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)-L-homoserine (see structure in Figure 1, Table 2). EXAMPLE 164, COMPOUND 124

[0796] N-(4-methyltetrahydro-2H-pyran-4-carbonyl)-O-(trans-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin- 2-yl)ethyl)cyclobutyl)homoserine. The D2 isomer was used in General Scheme D-2 using General Procedure I with 4-methyltetrahydro-2H-pyran-4-carboxylic acid. LCMS theoretical m/z = 460.28. [M+H]+, found 460.3. EXAMPLE 165, COMPOUND 125

[0797] N-(2-cyclohexyl-2-methylquinolinayl)-O-(trans-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl) ethyl)cyclobutyl)homoserine. The D2 isomer was used in General Scheme D-2 using General Procedure I with 2-cyclohexyl-2-methylpropanoic acid. LCMS theoretical m/z = 486.33. [M+H]+, found 486.3. EXAMPLE 166, COMPOUND 126

[0798] N-(2-(pyridin-2-yl)benzoyl)-O-(trans-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl )ethyl)cyclobutyl)homoserine. The D2 isomer was used in General Scheme D-2 using General Procedure I with 2-(pyridin-2-yl)benzoic acid. LCMS theoretical m/z = 515.27. [M+H]+, found 515.3. EXAMPLE 167, COMPOUND 127

[0799] N-(2-ethyl-4,4,4-trifluorobutanoyl)-O-(trans-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2- yl)ethyl)cyclobutyl)homoserine. The D2 isomer was used in General Scheme D-2 using General Procedure I with 2-ethyl-4,4,4-trifluorobutanoic acid. LCMS theoretical m/z = 486.26. [M+H]+, found 486.3. EXAMPLE 168, COMPOUND 128

[0800] N-(2-morpholinobenzoyl)-O-(trans-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine. The D2 isomer was used in General Scheme D-2 using General Procedure I with 2-morpholinobenzoic acid. LCMS theoretical m/z = 523.29. [M+H]+, found 523.3. EXAMPLE 169, COMPOUND 129

[0801] N-(2-ethyl-2-phenylbutanoyl)-O-(trans-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl) cyclobutyl)homoserine. The D2 isomer was used in General Scheme D-2 using General Procedure I with 2-ethyl-2-phenylbutanoic acid. LCMS theoretical m/z = 508.32. [M+H]+, found 508.3. EXAMPLE 170, COMPOUND 130

[0802] N-(1H-pyrrolo[3,2-b]pyridine-7-carbonyl)-O-(trans-3-(2- (5,6,7,8-tetrahydro-1,8- naphthyridin-2-yl)ethyl)cyclobutyl)homoserine. The D2 isomer was used in General Scheme D-2 using General Procedure I with 1H-pyrrolo[3,2-b]pyridine-7-carboxylic acid. LCMS theoretical m/z = 478.25. [M+H]+, found 478.4. EXAMPLE 171, COMPOUND 131

[0803] N-(4-cyanotetrahydro-2H-pyran-4-carbonyl)-O-(trans-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin- 2-yl)ethyl)cyclobutyl)homoserine. The D2 isomer was used in General Scheme D-2 using General Procedure I with 4-cyanotetrahydro-2H-pyran-4-carboxylic acid. LCMS theoretical m/z = 471.26. [M+H]+, found 471.3. EXAMPLE 172, COMPOUND 132

[0804] N-(1-(tert-butoxycarbonyl)-3-methylazetidine-3-carbonyl)- O-(trans-3-(2-(5,6,7,8-tetrahydro-1,8- naphthyridin-2-yl)ethyl)cyclobutyl)homoserine. The D2 isomer was used in General Scheme D-2 using General Procedure I with 1-(tert-butoxycarbonyl)-3-methylazetidine-3-carboxylic acid. LCMS theoretical m/z = 531.32. [M+H]+, found 531.3. EXAMPLE 173, COMPOUND 133 HO O

[0805] N-(1-(tert-butoxycarbonyl)azetidine-3-carbonyl)-O-(trans-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2 - yl)ethyl)cyclobutyl)homoserine. The D2 isomer was used in General Scheme D-2 using General Procedure I with 1-(tert-butoxycarbonyl)azetidine-3-carboxylic acid. LCMS theoretical m/z = 517.30. [M+H]+, found 517.3. EXAMPLE 174, COMPOUND 134 HO O

[0806] O-(trans-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)-N-(4-(trifluoromethyl)tetra -hydro-2H-pyran-4-carbonyl)homoserine. The D2 isomer was used in General Scheme D 2 using General Procedure I with 4-(trifluoromethyl)tetrahydro-2H-pyran-4-carboxylic acid, then General Procedure N. Theoretical LCMS m/z = 514.25. [M+H]+, found 514.3. EXAMPLE 175A, COMPOUND 135

[0807] N-(1-(methylsulfonyl)piperidine-3-carbonyl)-O-(trans-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl )ethyl)cyclobutyl)homoserine. The D2 isomer was used in General Scheme D-2 using General Procedure I with 1-(methylsulfonyl)piperidine-3-carboxylic acid, then General Procedure N followed by preparative HPLC to produce the title compound as the first eluting isomer. of unknown absolute stereochemistry in piperidine. LCMS theoretical m/z = 523.26. [M+H]+, found 523.3. The absolute stereochemistry of the product of Example 175a was subsequently assigned as N-((R)-1-(methylsulfonyl)piperidine-3-carbonyl)-O-((1s,3S)-3-(2-(5,6, 7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)-L-homoserine (see structure in Figure 1, Table 2). EXAMPLE 175B, COMPOUND 135

[0808] N-(1-(methylsulfonyl)piperidine-3-carbonyl)-O-(trans-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl )ethyl)cyclobutyl)homoserine. The D2 isomer was used in General Scheme D-2 using General Procedure I with 1-(methylsulfonyl)piperidine-3-carboxylic acid, then General Procedure N followed by preparative HPLC to produce the title compound as the second eluting isomer. of unknown absolute stereochemistry in piperidine. LCMS theoretical m/z = 523.26. [M+H]+, found 523.3. The absolute stereochemistry of the product of Example 175b was subsequently assigned as N-((S)-1-(methylsulfonyl)piperidine-3-carbonyl)-O-((1s,3S)-3-(2-(5,6, 7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)-L-homoserine (see structure in Figure 1, Table 2). EXAMPLE 176A, COMPOUND 136

[0809] O-(trans-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)-N-(4,5,6, 7-tetrahydro-1H-indazol-6-carbonyl)homoserine. The D2 isomer was used in General Scheme D2 using General Procedure I with 4,5,6,7-tetrahydro-1H-indazole-6-carboxylic acid, then General Procedure N followed by preparative HPLC to generate the compound of the title as the first eluting isomer of unknown absolute stereochemistry in cyclohexylpyrazole. LCMS theoretical m/z = 482.28. [M+H]+, found 482.3. The absolute stereochemistry of the product of Example 176a was subsequently assigned as O-((1s,3S)-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl )cyclobutyl)-N-((R)-4,5,6,7-tetrahydro-1H-indazol-6-carbonyl)-L-homoserine (see structure in Figure 1, Table 2). EXAMPLE 176B, COMPOUND 136

[0810] O-(trans-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)-N-(4,5,6, 7-tetrahydro-1H-indazol-6-carbonyl)homoserine. The D2 isomer was used in General Scheme D-2 using General Procedure I with 4,5,6,7-tetrahydro-1H-indazole-6-carboxylic acid, then General Procedure N followed by preparative HPLC to separate the diastereomers as the second eluting isomer of unknown absolute stereochemistry in cyclohexylpyrazole. LCMS theoretical m/z = 482.28. [M+H]+, found 482.3. The absolute stereochemistry of the product of Example 176b was subsequently assigned as O-((1s,3S)-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl )cyclobutyl)-N-((S)-4,5,6,7-tetrahydro-1H-indazol-6-carbonyl)-L-homoserine (see structure in Figure 1, Table 2). EXAMPLE 177, COMPOUND 137

[0811] O-(trans-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)-N-(4,5,6, 7-tetrahydro-1H-indazol-7-carbonyl)homoserine. The D2 isomer was used in General Scheme D2 using General Procedure I with 4,5,6,7-tetrahydro-1H-indazole-7-carboxylic acid. LCMS theoretical m/z = 482.28. [M+H]+, found 482.3. EXAMPLE 178, COMPOUND 124

[0812] N-(4-methyltetrahydro-2H-pyran-4-carbonyl)-O-(cis-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin- 2-yl)ethyl)cyclobutyl)homoserine. Prepared according to General Scheme B using General Procedure I with 4-methyltetrahydro-2H-pyran-4-carboxylic acid. LCMS theoretical m/z = 460.28. [M+H]+, found 460.3. EXAMPLE 179, COMPOUND 124

[0813] N-(4-methyltetrahydro-2H-pyran-4-carbonyl)-O-(cis-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin- 2-yl)ethyl)cyclobutyl) homoserine. The E2 isomer was used in General Scheme E-2 using General Procedure I with 4-methyltetrahydro-2H-pyran-4-carboxylic acid. LCMS theoretical m/z = 460.3 [M+H]+, found 460.3. EXAMPLE 180A, COMPOUND 138

[0814] N-((R)-1-methyl-4,5,6,7-tetrahydro-1H-indazol-6-carbonyl)- O-(trans-3-(2-(5,6, 7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine. The D2 isomer was used in General Scheme D-2 using General Procedure I with 1-methyl-4,5,6,7-tetrahydro-1H-indazole-6-carboxylic acid, then General Procedure N followed by HPLC preparative to obtain the first elution of two diastereomers as a single stereoisomer. LCMS theoretical m/z = 496.29. [M+H]+, found 496.3. The absolute stereochemistry of the product of Example 180a was subsequently assigned as N-((R)-1-methyl-4,5,6,7-tetrahydro-1H-indazol-6-carbonyl)-O-((1s, 3S)-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)-L-homoserine (see structure in Figure 1, Table 2). EXAMPLE 180B, COMPOUND 138

[0815] N-((S)-1-methyl-4,5,6,7-tetrahydro-1H-indazol-6-carbonyl)- O-(trans-3-(2-(5,6, 7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine. The D2 isomer was used in General Scheme D-2 using General Procedure I with 1-methyl-4,5,6,7-tetrahydro-1H-indazole-6-carboxylic acid, then General Procedure N followed by HPLC preparative to obtain the second elution of two diastereomers as a single stereoisomer. LCMS theoretical m/z = 496.29. [M+H]+, found 496.3. The absolute stereochemistry of the product of Example 180b was subsequently assigned as N-((S)-1-methyl-4,5,6,7-tetrahydro-1H-indazol-6-carbonyl)-O-((1s, 3S)-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)-L-homoserine (see structure in Figure 1, Table 2). EXAMPLE 181, COMPOUND 139

[0816] N-(1-ethyl-4,4-difluorocyclohexane-1-carbonyl)-O-(trans-3- (2-(5,6,7,8-tetrahydro-1,8- naphthyridin-2-yl)ethyl)cyclobutyl)homoserine. The D2 isomer was used in General Scheme D-2 using General Procedure I with 1-ethyl-4,4-difluorocyclohexane-1-carboxylic acid. LCMS theoretical m/z = 508.3. [M+H]+, found 508.3. EXAMPLE 182, COMPOUND 140

[0817] N-(1-(6-methylindoline-1-carbonyl)cyclopropane-1-carbonyl)-O-(trans-3-(2-(5,6,7,8-tetrahydro-1,8 -naphthyridin-2- yl)ethyl)cyclobutyl)homoserine. The D2 isomer was used in General Scheme D-2 using General Procedure I with 1-(6-methylindoline-1-carbonyl)cyclopropane-1-carboxylic acid. LCMS theoretical m/z = 561.3. [M+H]+, found 561.3. EXAMPLE 183, COMPOUND 134

[0818] O-(cis-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)-N-(4-(trifluoromethyl)tetra -hydro-2H-pyran-4-carbonyl)homoserine. The E2 isomer was used in General Scheme E-2 using General Procedure I with 4-trifluoromethyltetrahydro-2H-pyran-4-carboxylic acid. LCMS theoretical m/z = 514.2 [M+H]+, found 514.2. EXAMPLE 184, COMPOUND 141

[0819] N-(4-(((tert-butoxycarbonyl)amino)methyl) tetrahydro-2H-pyran-4-carbonyl)-O-(cis-3-(2-(5,6,7,8 -tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine. The E2 isomer was used in General Scheme E-2 using General Procedure I with 4-((((tert-butoxycarbonyl)amino)methyl)tetrahydro-2H-pyran-4-carboxylic acid. Theoretical LCMS m/z = 575.3 [M+H]+, found 575.3. EXAMPLE 185, COMPOUND 142.

[0820] N-(1-(pyridin-3-ylmethyl)cyclopropane-1-carbonyl)-O-(trans-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin -2- yl)ethyl)cyclobutyl)homoserine. The D2 isomer was used in General Scheme D-2 using General Procedure I with 1-(pyridin-3-ylmethyl)cyclopropane-1-carboxylic acid. LCMS theoretical m/z = 493.3. [M+H]+, found 493.2. EXAMPLE 186, COMPOUND 143

[0821] N-(3-chloro-5-methylisonicotinoyl)-O-(4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl)homoserine. Prepared according to General Scheme C using General Procedure I with 3-chloro-5-methylisonicotinic acid. LCMS theoretical m/z = 461.2 [M+H]+, found 461.2. EXAMPLE 187, COMPOUND 144

[0822] N-(4-methyltetrahydro-2H-pyran-4-carbonyl)-O-(4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl )homoserine. Prepared according to General Scheme C using General Procedure I with 4-methyltetrahydro-2H-pyran-4-carboxylic acid. LCMS theoretical m/z = 434.3 [M+H]+, found 434.3. EXAMPLE 188, COMPOUND 145

[0823] N-(2,6-dichlorobenzoyl)-O-(4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl)homoserine. Prepared according to General Scheme C using General Procedure I with 2,6-dichlorobenzoic acid. LCMS theoretical m/z = 480.1 [M+H]+, found 480.2. EXAMPLE 189, COMPOUND 146

[0824] N-(3,5-dichloroisonicotinoyl)-O-(4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl)homoserine. Prepared according to General Scheme C using General Procedure I with 3,5-dichloroisonicotinic acid. LCMS theoretical m/z = 481.1 [M+H]+, found 481.2. EXAMPLE 190, COMPOUND 147

[0825] N-(1-(4-(tert-butyl)phenyl)cyclobutane-1-carbonyl)-O-(trans-3-(2-(5,6,7,8-tetrahydro-1, 8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine. The D2 isomer was used in General Scheme D-2 using General Procedure I with 1-(4-(tert-butyl)phenyl)cyclobutane-1-carboxylic acid. LCMS theoretical m/z = 548.3. [M+H]+, found 548.3. EXAMPLE 191, COMPOUND 124

[0826] N-(4-methyltetrahydro-2H-pyran-4-carbonyl)-O-(cis-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin- 2-yl)ethyl)cyclobutyl)homoserine. The E1 isomer was used in General Scheme E-2 using General Procedure I with 4-methyltetrahydro-2H-pyran-4-carboxylic acid. LCMS theoretical m/z = 460.3. [M+H]+, found 460.3. EXAMPLE 192, COMPOUND 134

[0827] O-(cis-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)-N-(4-(trifluoromethyl)tetra -hydro-2H-pyran-4-carbonyl)homoserine. The E1 isomer was used in General Scheme E-2 using General Procedure I with 4-(trifluoromethyl)tetrahydro-2H-pyran-4-carboxylic acid. LCMS theoretical m/z = 514.3. [M+H]+, found 514.3. EXAMPLE 193, COMPOUND 148

[0828] N-(3,5-dimethylisonicotinoyl)-O-(cis-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl) homoserine. The E1 isomer was used in General Scheme E-2 using General Procedure I with 3,5-dimethylisonicotinic acid. LCMS theoretical m/z = 467.3. [M+H]+, found 467.3. EXAMPLE 194, COMPOUND 149

[0829] N-(3-chloro-5-methylisonicotinoyl)-O-(cis-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl) cyclobutyl)homoserine. The E1 isomer was used in General Scheme E-2 using General Procedure I with 3-chloro-5-methylisonicotinic acid. LCMS theoretical m/z = 487.2 [M+H]+, found 487.2. EXAMPLE 195, COMPOUND 150

[0830] N-(3,5-dichloroisonicotinoyl)-O-(cis-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl) homoserine. The E2 isomer was used in General Scheme E-2 using General Procedure I with 3,5-dichloroisonicotinic acid. LCMS theoretical m/z = 507.1 [M+H]+, found 507.1. EXAMPLE 196, COMPOUND 151

[0831] N-(bicyclo[2.2.2]octane-2-carbonyl)-O-(trans-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2- yl)ethyl)cyclobutyl)homoserine. The D2 isomer was used in General Scheme D-2 using General Procedure I with bicyclo[2.2.2]octane-2-carboxylic acid. LCMS theoretical m/z = 470.3. [M+H]+, found 470.3. EXAMPLE 197, COMPOUND 152

[0832] N-(2-methyl-1,2,3,4-tetrahydronaphthialene-2-carbonyl)-O- (trans-3-(2-(5,6,7,8-tetrahydro- 1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine. The D2 isomer was used in General Scheme D-2 using General Procedure I with 2-methyl-1,2,3,4-tetrahydronaphthalene-2-carboxylic acid. LCMS theoretical m/z = 430.27. [M+H]+, found 430.3. EXAMPLE 198, COMPOUND 153

[0833] N-((methylsulfonyl)prolyl)-O-(trans-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine . The D2 isomer was used in General Scheme D-2 using General Procedure I with (methylsulfonyl)proline. LCMS theoretical m/z = 509.2. [M+H]+, found 509.3. EXAMPLE 199, COMPOUND 149

[0834] N-(3-chloro-5-methylisonicotinoyl)-O-(cis-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl) cyclobutyl)homoserine. The E2 isomer was used in General Scheme E-2 using General Procedure I with 3-chloro-5-methylisonicotinic acid. LCMS theoretical m/z = 487.2 [M+H]+, found 487.2. EXAMPLE 200, COMPOUND 154

[0835] N-(2,4-dimethylnicotinoyl)-O-(cis-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl) homoserine. The E2 isomer was used in General Scheme E-2 using General Procedure I with 2,4-dimethylnicotinic acid. LCMS theoretical m/z = 467.3 [M+H]+, found 467.3. EXAMPLE 201, COMPOUND 155

[0836] N-(4-phenyltetrahydro-2H-pyran-4-carbonyl)-O-(trans-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin- 2-yl)ethyl)cyclobutyl)homoserine. The D2 isomer was used in General Scheme D-2 using General Procedure I with 4-phenyltetrahydro-2H-pyran-4-carboxylic acid. LCMS theoretical m/z = 522.3. [M+H]+, found 522.2. EXAMPLE 202, COMPOUND 156

[0837] N-(4-cyano-2,6-dimethylbenzoyl)-O-(cis-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl) ethyl)cyclobutyl)homoserine. The E2 isomer was used in General Scheme E-2 using General Procedure I with 4-cyano-2,6-dimethylbenzoic acid. LCMS theoretical m/z = 491.3 [M+H]+, found 491.3. EXAMPLE 203, COMPOUND 157

[0838] O-(cis-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)-N-(2,4,6- trimethylpyrimidine-5-carbonyl)homoserine. The E2 isomer was used in General Scheme E-2 using General Procedure I with 2,4,6-trimethylpyrimidine-5-carboxylic acid. LCMS theoretical m/z = 482.3 [M+H]+, found 482.2. EXAMPLE 204, COMPOUND 158

[0839] O-(cis-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)-N-(2,4,6- trimethylnicotinoyl)homoserine. The E2 isomer was used in General Scheme E-2 using General Procedure I with 2,4,6-trimethylnicotinic acid. LCMS theoretical m/z = 481.3 [M+H]+, found 481.2. EXAMPLE 205, COMPOUND 159

[0840] N-(3-chloro-5-fluoroisonicotinoyl)-O-(cis-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl) cyclobutyl)homoserine. The E2 isomer was used in General Scheme E-2 using General Procedure I with 3-chloro-5-fluoroisonicotinic acid. LCMS theoretical m/z = 491.2 [M+H]+, found 491.1. EXAMPLE 206, COMPOUND 160

[0841] N-(1-(isoquinolin-1-yl)cyclopropane-1-carbonyl)-O-(trans-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin -2- yl)ethyl)cyclobutyl)homoserine. The D2 isomer was used in General Scheme D-2 using General Procedure I with 1-(isoquinolin-1-yl)cyclopropane-1-carboxylic acid. LCMS theoretical m/z = 529.3. [M+H]+, found 529.3. EXAMPLE 207, COMPOUND 161

[0842] N-(2-(pyridin-2-yl)spiro[3.3]heptane-2-carbonyl)-O-(trans- 3-(2-(5,6,7,8-tetrahydro-1 ,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine. The D2 isomer was used in General Scheme D-2 using General Procedure I with 2-(pyridin-2-yl)spiro[3.3]heptane-2-carboxylic acid. LCMS theoretical m/z = 533.3. [M+H]+, found 533.3. EXAMPLE 208, COMPOUND 162

[0843] N-(2-(1-methyl-1H-pyrazol-4-yl)tetrahydrofuran-2-carbonyl)- O-(trans-3-(2-(5,6,7,8-tetra -hydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine. The D2 isomer was used in General Scheme D-2 using General Procedure I with 2-(1-methyl-1H-pyrazol-4-yl)tetrahydrofuran-2-carboxylic acid, then General Procedure N followed by preparative HPLC to generate the title compound as the first eluting isomer. LCMS theoretical m/z = 512.3. [M+H]+, found 512.3. EXAMPLE 209, COMPOUND 162

[0844] N-(2-(1-methyl-1H-pyrazol-4-yl)tetrahydrofuran-2-carbonyl)- O-(trans-3-(2-(5,6,7,8-tetra -hydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine. The D2 isomer was used in General Scheme D-2 using General Procedure I with 2-(1-methyl-1H-pyrazol-4-yl)tetrahydrofuran-2-carboxylic acid, then General Procedure N followed by preparative HPLC to generate the title compound as the second elution isomer. LCMS theoretical m/z = 512.3. [M+H]+, found 512.3. EXAMPLE 210, COMPOUND 163

[0845] N-(2,4-dimethyl-6-oxo-1,6-dihydropyridine-3-carbonyl)-O- (cis-3-(2-(5,6,7,8-tetra- hydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine. The E2 isomer was used in General Scheme E-2 using General Procedure I with 2,4-dimethyl-6-oxo-1,6-dihydropyridine-3-carboxylic acid. LCMS theoretical m/z = 491.2 [M+H]+, found 491.1. EXAMPLE 211, COMPOUND 164

[0846] N-(4,6-dimethylpyrimidine-5-carbonyl)-O-(cis-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl) ethyl)cyclobutyl)homoserine. The E2 isomer was used in General Scheme E-2 using General Procedure I with 4,6-dimethylpyrimidine-5-carboxylic acid. LCMS theoretical m/z = 468.3 [M+H]+, found 468.2. EXAMPLE 212, COMPOUND 165

[0847] N-(2,6-dichloro-4-(trifluoromethyl)benzoyl)-O-(cis-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2 -yl)ethyl)cyclobutyl)homoserine. The E2 isomer was used in General Scheme E-2 using General Procedure I with 2,6-dichloro-4-(trifluoromethyl)benzoic acid. LCMS theoretical m/z = 574.1 [M+H]+, found 574.1. EXAMPLE 213, COMPOUND 166

[0848] N-(1-(2-fluorophenyl)cyclopropane-1-carbonyl)-O-(trans-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2 -yl)ethyl)cyclobutyl)homoserine. The D2 isomer was used in General Scheme D-2 using General Procedure I with 1-(2-fluorophenyl)cyclopropane-1-carboxylic acid. LCMS theoretical m/z = 512.3. [M+H]+, found 512.3. EXAMPLE 214, COMPOUND 167

[0849] N-(1-(benzo[d][1,3]dioxol-5-yl)cyclohexane-1-carbonyl)- O-(trans-3-(2-(5,6,7, 8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine. The D2 isomer was used in General Scheme D-2 using General Procedure I with 1-(benzo[d][1,3]dioxol-5-yl)cyclopropane-1-carboxylic acid. LCMS theoretical m/z = 564.3. [M+H]+, found 564.3. EXAMPLE 215, COMPOUND 168

[0850] N-(2,2-difluoro-1-(m-tolyl)cyclopropane-1-carbonyl)-O-(trans-3-(2-(5,6,7,8-tetrahydro-1 ,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine. The D2 isomer was used in General Scheme D-2 using General Procedure I with 2,2-difluoro-1-(m-tolyl)cyclopropane-1-carboxylic acid. LCMS theoretical m/z = 528.3. [M+H]+, found 528.3. EXAMPLE 216, COMPOUND 169

[0851] O-(trans-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)-N-(1-(tetrahydro -2H-pyran-2-yl)cyclopropane-1-carbonyl)homoserine. The D2 isomer was used in General Scheme D2 using General Procedure I with 1-(tetrahydro-2H-pyran-2-yl)cyclopropane-1-carboxylic acid. LCMS theoretical m/z = 486.3. [M+H]+, found 486.3. EXAMPLE 217, COMPOUND 170

[0852] N-(4-methoxy-2,6-dimethylbenzoyl)-O-(cis-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl) ethyl)cyclobutyl)homoserine. The E2 isomer was used in General Scheme E-2 using General Procedure I with 4-methoxy-2,6-dimethylbenzoic acid. LCMS theoretical m/z = 496.3 [M+H]+, found 496.2. EXAMPLE 218, COMPOUND 171

[0853] N-(1-acetyl-4-(trifluoromethyl)piperidine-4-carbonyl)-O-(cis-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin -2- yl)ethyl)cyclobutyl)homoserine. The E2 isomer was sequentially used in General Procedure D, General Procedure I with 1-(tert-butoxycarbonyl)-4-(trifluoromethyl)piperidine-4-carboxylic acid, General Procedure D, General Procedure L, and General Procedure N LCMS theoretical m/z = 496.3 [M+H]+, found 496.2. EXAMPLE 219, COMPOUND 172

[0854] N-(2,3-dihydrobenzo[b][1,4]dioxin-2-carbonyl)-O-(trans- 3-(2-(5,6,7,8-tetrahydro -1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine. The D2 isomer was used in General Scheme D-2 using General Procedure I with 2,3-dihydrobenzo[b][1,4]dioxin-2-carboxylic acid. LCMS theoretical m/z = 496.2. [M+H]+, found 496.2. EXAMPLE 220, COMPOUND 173

[0855] N-(1-(3-chlorobenzyl)cyclopentane-1-carbonyl)-O-(trans-3- (2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2 -yl)ethyl)cyclobutyl)homoserine. The D2 isomer was used in General Scheme D-2 using General Procedure I with 1-(3-chlorobenzyl)cyclopentane-1-carboxylic acid. LCMS theoretical m/z = 554.3. [M+H]+, found 554.3. EXAMPLE 221, COMPOUND 174

[0856] O-(trans-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)-N-(1-(3-( trifluoromethoxy)phenyl)cyclopropane-1-carbonyl)homoserine. The D2 isomer was used in General Scheme D2 using General Procedure I with 1-(3-(trifluoromethoxy)phenyl)cyclopropane-1-carboxylic acid. LCMS theoretical m/z = 562.2. [M+H]+, found 562.2. EXAMPLE 222, COMPOUND 175

[0857] N-(4-fluoro-2,6-dimethylbenzoyl)-O-(cis-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl) ethyl)cyclobutyl)homoserine. The E2 isomer was used in General Scheme E-2 using General Procedure I with 4-fluoro-2,6-dimethylbenzoic acid. LCMS theoretical m/z = 484.3 [M+H]+, found 484.2. EXAMPLE 223, COMPOUND 148

[0858] N-(3,5-dimethylisonicotinoyl)-O-(cis-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl) homoserine. The E2 isomer was used in General Scheme E-2 using General Procedure I with 3,5-dimethylisonicotinic acid. LCMS theoretical m/z = 467.3 [M+H]+, found 467.2. EXAMPLE 224, COMPOUND 178

[0859] N-(quinazolin-4-yl)-O-(trans-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl) homoserine. Prepared according to General Scheme A using General Procedure E with 4-chloroquinazoline. LCMS theoretical m/z = 462.3. [M+H]+, found 462.3. EXAMPLE 225, COMPOUND 187

[0860] N-(2-(tert-butyl)pyrimidin-4-yl)-O-(trans-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2 -yl)ethyl)cyclobutyl)homoserine. The D2 isomer was used in General Scheme D-2 using General Procedure E with 2-tert-butyl-4-chloro-pyrimidine. LCMS theoretical m/z = 468.3 [M+H]+, found 468.3. EXAMPLE 226, COMPOUND 188

[0861] N-(4-(tert-butyl)pyrimidin-2-yl)-O-(trans-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2 -yl)ethyl)cyclobutyl)homoserine. The D2 isomer was used in General Scheme D-2 using General Procedure E with 4-(tert-butyl)-2-chloropyrimidine. LCMS theoretical m/z = 468.3 [M+H]+, found 468.3. EXAMPLE 227, COMPOUND 178

[0862] O-(trans-3-(2-(1,8-naphthyridin-2-yl)ethyl)cyclobutyl)-N-(quinazolin-4-yl)homoserine. The D1 isomer was used in General Scheme D-2 following General Procedure E with 4-chloroquinazoline. LCMS theoretical m/z = 462.3 [M+H]+, found 462.3. EXAMPLE 228, COMPOUND 178

[0863] O-(trans-3-(2-(1,8-naphthyridin-2-yl)ethyl)cyclobutyl)-N-(quinazolin-4-yl)homoserine. The D2 isomer was used in General Scheme D-2 following General Procedure E with 4-chloroquinazoline. LCMS theoretical m/z = 462.3 [M+H]+, found 462.3. EXAMPLE 229, COMPOUND 186

[0864] N-(6-(tert-butyl)pyrimidin-4-yl)-O-(trans-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2 -yl)ethyl)cyclobutyl)homoserine. The D2 isomer was used in General Scheme D-2 using General Procedure E with 4-(tert-butyl)-6-chloropyrimidine. LCMS theoretical m/z = 468.3 [M+H]+, found 468.3. EXAMPLE 230, COMPOUND 210 H2N

[0865] N-(4-amino-2,6-dichlorobenzoyl)-O-((1r,3R)-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin- 2-yl)ethyl)cyclobutyl)-L-homoserine. The E2 isomer was used in General Scheme E-2 using General Procedure I with 4-amino-2,6-dichlorobenzoic acid. LCMS theoretical m/z = 520.2. [M+H]+, found 521.1. EXAMPLE 231, COMPOUND 211

[0866] N-(4-chloro-2,6-dimethylnicotinoyl)-O-((1r,3R)-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin- 2-yl)ethyl)cyclobutyl)-L-homoserine. The E2 isomer was used in General Scheme E-2 using General Procedure I with 4-chloro-2,6-dimethylnicotinic acid. LCMS theoretical m/z = 500.2. [M+H]+, found 501.2. EXAMPLE 232, COMPOUND 212

[0867] N-(3-chloro-6-methylpicolinoyl)-O-((1r,3R)-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2- yl)ethyl)cyclobutyl)-L-homoserine. The E2 isomer was used in General Scheme E-2 using General Procedure I with 3-chloro-6-methylpicolinic acid. LCMS theoretical m/z = 486.2. [M+H]+, found 487.2. EXAMPLE 233, COMPOUND 213

[0868] N-((2R,6S)-2,6-dimethylpiperidine-1-carbonyl)-O-((1r,3R)-3- (2-(5,6,7,8-tetrahydro- 1,8-naphthyridin-2-yl)ethyl)cyclobutyl)-L-homoserine. The E2 isomer was used in General Scheme E-2 using General Procedure G with (2R,6S)-2,6-dimethylpiperidine. LCMS theoretical m/z = 472.3. [M+H]+, found 473.3. EXAMPLE 234, COMPOUND 214

[0869] N-((2R,5S)-2,5-dimethylpyrrolidine-1-carbonyl)-O-((1r,3R)-3- (2-(5,6,7,8-tetrahydro- 1,8-naphthyridin-2-yl)ethyl)cyclobutyl)-L-homoserine. The E2 isomer was used in General Scheme E-2 using General Procedure G with (2R,5S)-2,5-dimethylpyrrolidine. LCMS theoretical m/z = 458.3. [M+H]+, found 459.3. EXAMPLE 235, COMPOUND 215

[0870] N-((2R,5R)-2,5-dimethylpyrrolidine-1-carbonyl)-O-((1r,3R)-3- (2-(5,6,7,8-tetrahydro- 1,8-naphthyridin-2-yl)ethyl)cyclobutyl)-L-homoserine. The E2 isomer was used in General Scheme E-2 using General Procedure G with (2R,5R)-2,5-dimethylpyrrolidine. LCMS theoretical m/z = 458.3. [M+H]+, found 459.3. EXAMPLE 236, COMPOUND 216

[0871] N-(2,6-dichloro-4-cyanobenzoyl)-O-((1r,3R)-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin- 2-yl)ethyl)cyclobutyl)-L-homoserine. The E2 isomer was used in General Scheme E-2 using General Procedure I with 2,6-dichloro-4-cyanobenzoic acid. LCMS theoretical m/z = 530.1. [M+H]+, found 531.1. EXAMPLE 237, COMPOUND 217

[0872] N-(2,6-dichloro-3-nitrobenzoyl)-O-((1r,3R)-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin- 2-yl)ethyl)cyclobutyl)-L-homoserine. The E2 isomer was used in General Scheme E-2 using General Procedure I with 2,6-dichloro-3-nitrobenzoic acid. LCMS theoretical m/z = 550.2. [M+H]+, found 551.2. EXAMPLE 238, COMPOUND 218

[0873] O-((1r,3R)-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)-N-(1, 2,4-trimethyl-6-oxo-1,6-dihydropyridine-3-carbonyl)-L-homoserine. The E2 isomer was used in General Scheme E-2 using General Procedure I with 1,2,4-trimethyl-6-oxo-1,6-dihydropyridine-3-carboxylic acid. LCMS theoretical m/z = 496.3. [M+H]+, found 497.3. EXAMPLE 239, COMPOUND 219

[0874] N-(2-chloro-4-cyano-6-methylbenzoyl)-O-((1r,3R)-3-(2- (5,6,7,8-tetrahydro-1,8- naphthyridin-2-yl)ethyl)cyclobutyl)-L-homoserine. The E2 isomer was used in General Scheme E-2 using General Procedure I with 2-chloro-4-cyano-6-methylbenzoic acid. LCMS theoretical m/z = 510.2. [M+H]+, found 511.2. EXAMPLE 240, COMPOUND 220

[0875] N-(3-bromo-5-chloro-2-fluoroisonicotinoyl)-O-((1r,3R)-3- (2-(5,6,7,8-tetrahydro-1,8- naphthyridin-2-yl)ethyl)cyclobutyl)-L- homoserine. The E2 isomer was used in General Scheme E-2 using General Procedure I with 3-bromo-5-chloro-2-fluoroisonicotinic acid. LCMS theoretical m/z = 568.1. [M+H]+, found 569.1. EXAMPLE 241, COMPOUND 221

[0876] O-((1r,3R)-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)-N-(5, 6,7,8-tetrahydronaphthyalene-1-carbonyl)-L-homoserine. The E2 isomer was used in General Scheme E-2 using General Procedure I with 5,6,7,8-tetrahydronaphthalene-1-carboxylic acid. LCMS theoretical m/z = 491.3. [M+H]+, found 492.3. EXAMPLE 242, COMPOUND 222

[0877] N-(3-bromo-2,6-dimethylbenzoyl)-O-((1r,3R)-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin- 2-yl)ethyl)cyclobutyl)-L-homoserine. The E2 isomer was used in General Scheme E-2 using General Procedure I with 3-bromo-2,6-dimethylbenzoic acid. LCMS theoretical m/z = 543.2. [M+H]+, found 544.2. EXAMPLE 243, COMPOUND 223

[0878] N-(3-chloro-5-methoxy-isonicotinoyl)-O-((1r,3R)-3-(2- (5,6,7,8-tetrahydro-1,8-naphthyridin- 2-yl)ethyl)cyclobutyl)-L-homoserine The E2 isomer was used in General Scheme E-2 using General Procedure I with 3-chloro-5-methoxyisonicotinic acid. LCMS theoretical m/z = 502.2. [M+H]+, found 503.2. EXAMPLE 244, COMPOUND 224

[0879] N-(2,6-dichloro-4-fluorobenzoyl)-O-((1r,3R)-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin- 2-yl)ethyl)cyclobutyl)-L-homoserine. The E2 isomer was used in General Scheme E-2 using General Procedure I with 2,6-dichloro-4-fluorobenzoic acid. LCMS theoretical m/z = 523.1. [M+H]+, found 524.1. EXAMPLE 245, COMPOUND 225

[0880] N-(2-chloro-6-fluorobenzoyl)-O-((1r,3R)-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2- yl)ethyl)cyclobutyl)-L-homoserine. The E2 isomer was used in General Scheme E-2 using General Procedure I with 2-chloro-6-fluorobenzoic acid. LCMS theoretical m/z = 489.2. [M+H]+, found 489.9. EXAMPLE 246, COMPOUND 226

[0881] N-(3-bromo-2-chloro-6-fluorobenzoyl)-O-((1r,3R)-3-(2- (5,6,7,8-tetrahydro-1,8- naphthyridin-2-yl)ethyl)cyclobutyl)-L-homoserine. The E2 isomer was used in General Scheme E-2 using General Procedure I with 3-bromo-2-chloro-6-fluorobenzoic acid. LCMS theoretical m/z = 567.1. [M+H]+, found 568.1. EXAMPLE 247, COMPOUND 227

[0882] N-(2,4-dimethyl-6-oxo-1-phenyl-1,6-dihydropyridine-3-carbonyl)-O-((1r,3R)-3-(2-(5, 6,7,8-tetrahydro-1,8-naphthyridin-2- yl)ethyl)cyclobutyl)-L-homoserine Isomer E2 was used in General Scheme E-2 using General Procedure I with acid 2,4- dimethyl-6-oxo-1-phenyl-1,6-dihydropyridine-3-carboxylic acid. LCMS theoretical m/z = 558.3. [M+H]+, found 559.3. EXAMPLE 248, COMPOUND 228

[0883] N-(5-bromo-2-hydroxy-isonicotinoyl)-O-((1r,3R)-3-(2- (5,6,7,8-tetrahydro-1,8-naphthyridin- 2-yl)ethyl)cyclobutyl)-L-homoserine. The E2 isomer was used in General Scheme E-2 using General Procedure I with 5-bromo-2-hydroxyisonicotinic acid. LCMS theoretical m/z = 532.1. [M+H]+, found 533.1. EXAMPLE 249, COMPOUND 229

[0884] N-(3-chloro-5-cyclopropylisonicotinoyl)-O-((1r,3R)-3-(2- (5,6,7,8-tetrahydro-1,8-naphthyridin-2- yl)ethyl)cyclobutyl)-L-homoserine. The E2 isomer was used in General Scheme E-2 using General Procedure I with 3-chloro-5-cyclopropylisonicotinic acid. LCMS theoretical m/z = 512.2. [M+H]+, found 513.2. EXAMPLE 250, COMPOUND 230

[0885] N-(3-chloro-5-ethylisonicotinoyl)-O-((1r,3R)-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2- yl)ethyl)cyclobutyl)-L-homoserine. The E2 isomer was used in General Scheme E-2 using General Procedure I with 3-chloro-5-ethylisonicotinic acid. LCMS theoretical m/z = 500.2. [M+H]+, found 501.2. EXAMPLE 251, COMPOUND 231

[0886] N-(3-chloro-5-ethylisonicotinoyl)-O-((1r,3R)-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2- yl)ethyl)cyclobutyl)-L-homoserine. The E2 isomer was used in General Scheme E-2 using General Procedure I with 3-cyano-2,6-dimethylbenzoic acid. LCMS theoretical m/z = 490.2. [M+H]+, found 491.2. EXAMPLE 252, COMPOUND 232

[0887] N-(3-bromo-5-fluoroisonicotinoyl)-O-((1r,3R)-3-(2- (5,6,7,8-tetrahydro-1,8-naphthyridin-2- yl)ethyl)cyclobutyl)-L-homoserine. The E2 isomer was used in General Scheme E-2 using General Procedure I with 3-bromo-5-fluoroisonicotinic acid. LCMS theoretical m/z = 534.1. [M+H]+, found 535.1. EXAMPLE 253, COMPOUND 233

[0888] N-(2-methoxy-3,5-dimethylisonicotinoyl)-O-((1r,3R)-3-(2- (5,6,7,8-tetrahydro-1,8-naphthyridin- 2-yl)ethyl)cyclobutyl)-L-homoserine. The E2 isomer was used in General Scheme E-2 using General Procedure I with 2-methoxy-3,5-dimethylisonicotinic acid. LCMS theoretical m/z = 496.2. [M+H]+, found 497.2. EXAMPLE 254, COMPOUND 234

[0889] N-(3-chloro-5-(trifluoromethyl)isonicotinoyl)-O-((1r,3R)-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin -2-yl)ethyl)cyclobutyl)-L-homoserine. The E2 isomer was used in General Scheme E-2 using General Procedure I with 3-chloro-5-(trifluoromethyl)isonicotinic acid. LCMS theoretical m/z = 540.2. [M+H]+, found 541.2. EXAMPLE 255, COMPOUND 235

[0890] N-(3-bromo-5-chloroisonicotinoyl)-O-((1r,3R)-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2- yl)ethyl)cyclobutyl)-L-homoserine. The E2 isomer was used in General Scheme E-2 using General Procedure I with 3-bromo-5-chloroisonicotinic acid. LCMS theoretical m/z = 550.1. [M+H]+, found 551.1. EXAMPLE 256, COMPOUND 236

[0891] N-(5-chloro-2-(dimethylamino)-3-methylisonicotinoyl)-O-((1r,3R)-3-(2-(5,6,7,8-tetrahydro-1, 8-naphthyridin-2-yl)ethyl)cyclobutyl)-L- homoserine. The E2 isomer was used in General Scheme E-2 using General Procedure I with 5-chloro-2-(dimethylamino)-3-methylisonicotinic acid. LCMS theoretical m/z = 509.3. [M+H]+, found 510.2. EXAMPLE 257, COMPOUND 237

[0892] N-(3-chloro-5-fluoro-2-methylisonicotinoyl)-O-((1r,3R)-3-(2- (5,6,7,8-tetrahydro-1,8- naphthyridin-2-yl)ethyl)cyclobutyl)-L-homoserine. The E2 isomer was used in General Scheme E-2 using General Procedure I with 3-chloro-5-fluoro-2-methylisonicotinic acid. LCMS theoretical m/z = 504.2. [M+H]+, found 505.1. EXAMPLE 258, COMPOUND 238

[0893] N-(2,6-dichloro-3-cyanobenzoyl)-O-((1r,3R)-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin- 2-yl)ethyl)cyclobutyl)-L-homoserine. The E2 isomer was used in General Scheme E-2 using General Procedure I with 2,6-dichloro-3-cyanobenzoic acid. LCMS theoretical m/z = 530.1. [M+H]+, found 531.1. EXAMPLE 259, COMPOUND 239

[0894] N-(3-methyl-5-(trifluoromethyl)isonicotinoyl)-O-((1r,3R)-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin -2-yl)ethyl)cyclobutyl)-L-homoserine. The E2 isomer was used in General Scheme E-2 using General Procedure I with 3-methyl-5-(trifluoromethyl)isonicotinic acid. LCMS theoretical m/z = 520.2. [M+H]+, found 521.2. EXAMPLE 260, COMPOUND 240

[0895] N-(2-hydroxy-3,5-dimethylisonicotinoyl)-O-((1r,3R)-3-(2- (5,6,7,8-tetrahydro-1,8-naphthyridin- 2-yl)ethyl)cyclobutyl)-L-homoserine. The E2 isomer was used in General Scheme E-2 using General Procedure I with 2-hydroxy-3,5-dimethylisonicotinic acid. LCMS theoretical m/z = 488.2. [M+H]+, found 483.2. EXAMPLE 261, COMPOUND 241

[0896] N-(3-cyano-2-hydroxy-6-methylisonicotinoyl)-O-((1r,3R)-3-(2- (5,6,7,8-tetrahydro-1,8- naphthyridin-2-yl)ethyl)cyclobutyl)-L-homoserine. The E2 isomer was used in General Scheme E-2 using General Procedure I with 3-cyano-2-hydroxy-6-methylisonicotinic acid. LCMS theoretical m/z = 493.2. [M+H]+, found 494.2. EXAMPLE 262, COMPOUND 242

[0897] N-(5-chloro-3-fluoro-2-methylisonicotinoyl)-O-((1r,3R)-3-(2- (5,6,7,8-tetrahydro-1,8- naphthyridin-2-yl)ethyl)cyclobutyl)-L-homoserine. The E2 isomer was used in General Scheme E-2 using General Procedure I with 5-chloro-3-fluoro-2-methylisonicotinic acid. LCMS theoretical m/z = 504.2. [M+H]+, found 505.2. EXAMPLE 263, COMPOUND 243

[0898] N-(6-methoxy-2,4-dimethylnicotinoyl)-O-((1r,3R)-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin- 2-yl)ethyl)cyclobutyl)-L-homoserine. The E2 isomer was used in General Scheme E-2 using General Procedure I with 6-methoxy-2,4-dimethylnicotinic acid. LCMS theoretical m/z = 496.2. [M+H]+, found 497.2. EXAMPLE 264, COMPOUND 244

[0899] N-(2,6-dimethyl-4-((4-methylpiperazin-1-yl)methyl)benzoyl)-O- ((1r,3R)-3-(2-(5,6,7, 8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)-L-homoserine. The E2 isomer was used in General Scheme E-2 using General Procedure I with 2,6-dimethyl-4-((4-methylpiperazin-1-yl)methyl)benzoic acid. LCMS theoretical m/z = 577.3. [M+H]+, found 578.3. EXAMPLE 265, COMPOUND 245

[0900] N-((phenylsulfonyl)-L-prolyl)-O-((1r,3R)-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2- yl)ethyl)cyclobutyl)-L-homoserine. The E2 isomer was used in General Scheme E-2 using General Procedure I with (phenylsulfonyl)-L-proline. LCMS theoretical m/z = 570.2. [M+H]+, found 571.2. EXAMPLE 266, COMPOUND 246

[0901] N-((3R,5S)-3,5-dimethylmorpholine-4-carbonyl)-O-((1r,3R)-3-(2- (5,6,7,8-tetrahydro- 1,8-naphthyridin-2-yl)ethyl)cyclobutyl)-L-homoserine. The E2 isomer was used in General Scheme E-2 using General Procedure G with (3R,5S)-3,5-dimethylmorpholine. LCMS theoretical m/z = 474.3. [M+H]+, found 475.3. EXAMPLE 267, COMPOUND 247

[0902] N-(5-chloro-3-fluoro-2-((4-methylpiperazin-1-yl)methyl)isonicotinoyl)-O-((1r,3R)-3-(2-(5,6, 7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)-L-homoserine. The E2 isomer was used in General Scheme E-2 using General Procedure I with 5-chloro-3-fluoro-2-((4-methylpiperazin-1-yl)methyl)isonicotinic acid. LCMS theoretical m/z = 602.3. [M+H]+, found 603.3. EXAMPLE 268, COMPOUND 248

[0903] N-(7-chloro-5-oxo-1,2,3,5-tetrahydroindolizine-8-carbonyl)-O-((1r,3R)-3-(2-(5,6, 7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)-L-homoserine. The E2 isomer was used in General Scheme E-2 using General Procedure I with 7-chloro-5-oxo-1,2,3,5-tetrahydroindolizine-8-carboxylic acid. LCMS theoretical m/z = 528.2. [M+H]+, found 529.2. EXAMPLE 269, COMPOUND 249

[0904] N-(2,6-difluoro-4-hydroxybenzoyl)-O-((1r,3R)-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin- 2-yl)ethyl)cyclobutyl)-L-homoserine. The E2 isomer was used in General Scheme E-2 using General Procedure I with 2,6-difluoro-4-hydroxybenzoic acid. LCMS theoretical m/z = 489.2. [M+H]+, found 490.2. EXAMPLE 270, COMPOUND 250

[0905] N-(4-chloro-1-methyl-1H-pyrazol-5-carbonyl)-O-((1r,3R)-3-(2- (5,6,7,8-tetrahydro- 1,8-naphthyridin-2-yl)ethyl)cyclobutyl)-L-homoserine. The E2 isomer was used in General Scheme E-2 using General Procedure I with 4-chloro-1-methyl-1H-pyrazol-5-carboxylic acid. LCMS theoretical m/z = 475.2. [M+H]+, found 476.2. EXAMPLE 271, COMPOUND 251

[0906] N-(1-methyl-1H-pyrazol-5-carbonyl)-O-((1r,3R)-3-(2-(5,6,7,8-tetrahydro-1,8- naphthyridin-2-yl)ethyl)cyclobutyl)-L-homoserine. The E2 isomer was used in General Scheme E-2 using General Procedure I with 1-methyl-1H-pyrazol-5-carboxylic acid. LCMS theoretical m/z = 441.2. [M+H]+, found 442.2. EXAMPLE 272, COMPOUND 252

[0907] N-(3-chloro-5-fluoroisonicotinoyl)-O-((1r,3S)-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2- yl)ethyl)cyclobutyl)-D-homoserine. The E1 isomer was used in General Scheme E-2 using General Procedure I with 3-chloro-5-fluoroisonicotinic acid. LCMS theoretical m/z = 490.2. [M+H]+, found 491.2. EXAMPLE 273, COMPOUND 253

[0908] N-((S)-1-(phenylsulfonyl)piperidine-2-carbonyl)-O-((1r,3R)-3- (2-(5,6,7,8-tetrahydro-1 ,8-naphthyridin-2-yl)ethyl)cyclobutyl)-L-homoserine. The E2 isomer was used in General Scheme E-2 using General Procedure I with (S)-1-(phenylsulfonyl)piperidine-2-carboxylic acid. LCMS theoretical m/z = 584.3. [M+H]+, found 585.2. EXAMPLE 274, COMPOUND 254

[0909] N-(3-chloro-5-fluoro-2-((4-methylpiperazin-1-yl)methyl)isonicotinoyl)-O-((1r,3R)-3-(2-(5,6, 7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)-L-homoserine. The E2 isomer was used in General Scheme E-2 using General Procedure I with 3-chloro-5-fluoro-2-((4-methylpiperazin-1-yl)methyl)isonicotinic acid. LCMS theoretical m/z = 602.3. [M+H]+, found 603.3. EXAMPLE 275, COMPOUND 255

[0910] N-(3,3-dimethylbutanoyl)-O-((1r,3R)-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl) ethyl)cyclobutyl)-L-homoserine The E2 isomer was used in General Scheme E-2 using General Procedure I with 3,3-dimethylbutanoic acid. LCMS theoretical m/z = 431.3. [M+H]+, found 432.3. EXAMPLE 276, COMPOUND 256

[0911] N-(2-phenylacetyl)-O-((1r,3R)-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl) cyclobutyl)-L-homoserine. The E2 isomer was used in General Scheme E-2 using General Procedure I with 2-phenylacetic acid. LCMS theoretical m/z = 451.3. [M+H]+, found 452.3. EXAMPLE 277, COMPOUND 257

[0912] O-((1r,3R)-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)-N-(4, 4,4-trifluoro-3,3-dimethylbutanoyl)-L-homoserine. The E2 isomer was used in General Scheme E-2 using General Procedure I with 4,4,4-trifluoro-3,3-dimethylbutanoic acid. LCMS theoretical m/z = 485.3. [M+H]+, found 486.3. EXAMPLE 278, COMPOUND 258

[0913] N-(4,4-difluoro-3,3-dimethylbutanoyl)-O-((1r,3R)-3-(2- (5,6,7,8-tetrahydro-1,8- naphthyridin-2-yl)ethyl)cyclobutyl)-L-homoserine. The E2 isomer was used in General Scheme E-2 using General Procedure I with 4,4-difluoro-3,3-dimethylbutanoic acid. LCMS theoretical m/z = 467.3. [M+H]+, found 468.3. EXAMPLE 279, COMPOUND 259

[0914] N-((S)-2-phenylquinolinayl)-O-((1r,3R)-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2- yl)ethyl)cyclobutyl)-L-homoserine. The E2 isomer was used in General Scheme E-2 using General Procedure I with (S)-2-phenylpropanoic acid. LCMS theoretical m/z = 465.3. [M+H]+, found 466.3. EXAMPLE 280, COMPOUND 260

[0915] N-(2-(3,5-difluorophenyl)acetyl)-O-((1r,3R)-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin -2-yl)ethyl)cyclobutyl)-L-homoserine. The E2 isomer was used in General Scheme E-2 using General Procedure I with 2-(3,5-difluorophenyl)acetic acid. LCMS theoretical m/z = 487.2. [M+H]+, found 488.2. EXAMPLE 281, COMPOUND 261

[0916] N-((((S)-1-((tert-butoxycarbonyl)amino)propan-2-yl)oxy)carbonyl)-O-((1s,3S)-3-(2-(5, 6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)-L-homoserine. The D2 isomer was used in General Scheme D-2 using General Procedure I with (S)-1-((tert-butoxycarbonyl)amino)propan-2-yl hydrogencarbonate. LCMS theoretical m/z = 534.3. [M+H]+, found 535.3. EXAMPLE 282, COMPOUND 262

[0917] N-(3,6-dimethylpicolinoyl)-O-((1r,3R)-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl) ethyl)cyclobutyl)-L-homoserine. The D2 isomer was used in General Scheme D-2 using General Procedure I with 3,6-dimethylpicolinic acid. LCMS theoretical m/z = 466.3. [M+H]+, found 467.3. EXAMPLE 283, COMPOUND 263

[0918] N-(6-fluorochromano-2-carbonyl)-O-((1s,3S)-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2- yl)ethyl)cyclobutyl)-L-homoserine. The D2 isomer was used in General Scheme D-2 using General Procedure I with 6-fluorochroman-2-carboxylic acid. LCMS theoretical m/z = 511.3. [M+H]+, found 512.3. EXAMPLE 284, COMPOUND 264

[0919] O-((1s,3S)-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)-N-(2- (3-(trifluoromethyl)phenyl)butanoyl)-L- homoserine. The D2 isomer was used in General Scheme D-2 using General Procedure I with 2-(3-(trifluoromethyl)phenyl)butanoic acid. LCMS theoretical m/z = 547.3. [M+H]+, found 548.3. EXAMPLE 285, COMPOUND 265

[0920] N-(3-chloro-5-methylisonicotinoyl)-O-((1s,3S)-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2- yl)ethyl)cyclobutyl)-L-homoserine. The D2 isomer was used in General Scheme D-2 using General Procedure I with 3-chloro-5-methylisonicotinic acid. LCMS theoretical m/z = 486.2. [M+H]+, found 487.2. EXAMPLE 286, COMPOUND 266

[0921] N-(3-chloro-5-fluoroisonicotinoyl)-O-((1s,3S)-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2- yl)ethyl)cyclobutyl)-L-homoserine. The D2 isomer was used in General Scheme D-2 using General Procedure I with 3-chloro-5-fluoroisonicotinic acid. LCMS theoretical m/z = 490.2. [M+H]+, found 491.2. EXAMPLE 287, COMPOUND 267

[0922] N-(4-cyano-2,6-dimethylbenzoyl)-O-((1s,3S)-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin- 2-yl)ethyl)cyclobutyl)-L-homoserine. The D2 isomer was used in General Scheme D-2 using General Procedure I with 4-cyano-2,6-dimethylbenzoic acid. LCMS theoretical m/z = 490.3. [M+H]+, found 491.3. EXAMPLE 288, COMPOUND 268

[0923] N-(4-(2-chlorophenyl)tetrahydro-2H-pyran-4-carbonyl)-O-((1s,3S)-3-(2-(5,6,7,8-tetra -hydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)-L-homoserine. The D2 isomer was used in General Scheme D-2 using General Procedure I with 4-(2-chlorophenyl)tetrahydro-2H-pyran-4-carboxylic acid. LCMS theoretical m/z = 555.3. [M+H]+, found 556.3. EXAMPLE 289, COMPOUND 269

[0924] N-(2-hydroxy-2,3-dihydro-1H-indene-2-carbonyl)-O- ((1s,3S)-3-(2-(5,6,7,8- tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)-L-homoserine. The D2 isomer was used in General Scheme D-2 using General Procedure I with 2-hydroxy-2,3-dihydro-1H-indene-2-carboxylic acid. LCMS theoretical m/z = 493.3. [M+H]+, found 494.2. EXAMPLE 290, COMPOUND 270

[0925] N-([1,1'-bi(cyclopropane)]-1-carbonyl)-O-((1s,3S)-3-(2- (5,6,7,8-tetrahydro- 1,8-naphthyridin-2-yl)ethyl)cyclobutyl)-L-homoserine. The D2 isomer was used in General Scheme D-2 using General Procedure I with [1,1'-bi(cyclopropane)]-1-carboxylic acid. LCMS theoretical m/z = 441.3. [M+H]+, found 442.3. EXAMPLE 291, COMPOUND 271

[0926] N-((S)-3-(difluoromethyl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyridine-6-carbonyl)- O-((1s,3S)-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)-L-homoserine. The D2 isomer was used in General Scheme D-2 using General Procedure I with 3-(difluoromethyl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3- a ]pyridine-6-carboxylic. LCMS theoretical m/z = 532.3. [M+H]+, found 533.3. EXAMPLE 292, COMPOUND 272

[0927] N-((R)-3-(difluoromethyl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyridine-6-carbonyl)- O-((1s,3S)-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)-L-homoserine. The D2 isomer was used in General Scheme D-2 using General Procedure I with 3-(difluoromethyl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3- a ]pyridine-6-carboxylic. LCMS theoretical m/z = 532.3. [M+H]+, found 533.3. EXAMPLE 293, COMPOUND 273

[0928] N-(1-cyclopropylcyclobutane-1-carbonyl)-O-((1s,3S)-3-(2- (5,6,7,8-tetrahydro-1,8-naphthyridin-2- yl)ethyl)cyclobutyl)-L-homoserine. The D2 isomer was used in General Scheme D-2 using General Procedure I with 1-cyclopropylcyclobutane-1-carboxylic acid. LCMS theoretical m/z = 455.3. [M+H]+, found 456, EXAMPLE 294, COMPOUND 274

[0929] N-(1-(4-isopropylphenyl)cyclopentane-1-carbonyl)-O-((1s,3S)-3-(2-(5,6,7,8-tetrahydro-1,8 -naphthyridin-2-yl)ethyl)cyclobutyl)-L- homoserine. The D2 isomer was used in General Scheme D-2 using General Procedure I with 1-(4-isopropylphenyl)cyclopentane-1-carboxylic acid. LCMS theoretical m/z = 547.3. [M+H]+, found 548.3. EXAMPLE 295, COMPOUND 275

[0930] N-(bicyclo[2.2.2]octane-1-carbonyl)-O-((1s,3S)-3-(2- (5,6,7,8-tetrahydro-1,8- naphthyridin-2-yl)ethyl)cyclobutyl)-L-homoserine. The D2 isomer was used in General Scheme D-2 using General Procedure I with bicyclo[2.2.2]octane-1-carboxylic acid. LCMS theoretical m/z = 469.3. [M+H]+, found 470.3. EXAMPLE 296, COMPOUND 276

[0931] N-(octahydrobenzofuran-3a-carbonyl)-O-((1s,3S)-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl) ethyl)cyclobutyl)-L-homoserine. The D2 isomer was used in General Scheme D-2 using General Procedure I with octahydrobenzofuran-4-carboxylic acid. LCMS theoretical m/z = 485.3. [M+H]+, found 486.3. EXAMPLE 297, COMPOUND 277

[0932] N-(1-phenethylcyclopropane-1-carbonyl)-O-((1s,3S)-3-(2- (5,6,7,8-tetrahydro-1,8-naphthyridin-2- yl)ethyl)cyclobutyl)-L-homoserine. The D2 isomer was used in General Scheme D-2 using General Procedure I with 1-phenethylcyclopropane-1-carboxylic acid. LCMS theoretical m/z = 505.3. [M+H]+, found 506.3. EXAMPLE 298, COMPOUND 278

[0933] N-(4-(3-methylisoxazol-5-yl)tetrahydro-2H-pyran-4-carbonyl)-O-((1s,3S)-3-(2-(5,6,7 ,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)-L-homoserine. The D2 isomer was used in General Scheme D-2 using General Procedure I with 4-(3-methylisoxazol-5-yl)tetrahydro-2H-pyran-4-carboxylic acid. LCMS theoretical m/z = 526.3. [M+H]+, found 527.1. EXAMPLE 299, COMPOUND 279

[0934] N-(1-(phenylsulfonyl)cyclopropane-1-carbonyl)-O-((1s,3S)-3- (2-(5,6,7,8-tetrahydro-1,8-naphthyridin -2-yl)ethyl)cyclobutyl)-L- homoserine. The D2 isomer was used in General Scheme D-2 using General Procedure I with 1-(phenylsulfonyl)cyclopropane-1-carboxylic acid. LCMS theoretical m/z = 541.2. [M+H]+, found 542.2. EXAMPLE 300, COMPOUND 280

[0935] N-(1-phenylcycloheptane-1-carbonyl)-O-((1s,3S)-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin- 2-yl)ethyl)cyclobutyl)-L-homoserine. The D2 isomer was used in General Scheme D-2 using General Procedure I with 1-phenylcycloheptane-1-carboxylic acid. LCMS theoretical m/z = 533.3. [M+H]+, found 534.3. EXAMPLE 301, COMPOUND 281

[0936] N-(4-(methylsulfonyl)tetrahydro-2H-pyran-4-carbonyl)-O-((1s,3S)-3-(2-(5,6,7,8-tetrahydro -1,8-naphthyridin-2-yl)ethyl)cyclobutyl)-L- homoserine. The D2 isomer was used in General Scheme D-2 using General Procedure I with 4-(methylsulfonyl)tetrahydro-2H-pyran-4-carboxylic acid. LCMS theoretical m/z = 523.2. [M+H]+, found 524.2. EXAMPLE 302, COMPOUND 282

[0937] N-(1-(4-sulfamoylphenyl)cyclopropane-1-carbonyl)-O-((1s,3S)-3-(2-(5,6,7,8-tetrahydro-1,8 -naphthyridin-2-yl)ethyl)cyclobutyl)-L- homoserine. The D2 isomer was used in General Scheme D-2 using General Procedure I with 1-(4-sulfamoylphenyl)cyclopropane-1-carboxylic acid. LCMS theoretical m/z = 556.2. [M+H]+, found 557.2. EXAMPLE 303, COMPOUND 283

[0938] N-((phenylsulfonyl)-L-prolyl)-O-((1s,3S)-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2- yl)ethyl)cyclobutyl)-L-homoserine. The D2 isomer was used in General Scheme D-2 using General Procedure I with (phenylsulfonyl)-L-proline. LCMS theoretical m/z = 570.2. [M+H]+, found 571.2. EXAMPLE 304, COMPOUND 284

[0939] N-(5-chloro-3-fluoro-2-((4-methylpiperazin-1-yl)methyl)isonicotinoyl)-O-((1s,3S)-3-(2-(5,6, 7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)-L-homoserine. The D2 isomer was used in General Scheme D-2 using General Procedure I with 5-chloro-3-fluoro-2-((4-methylpiperazin-1-yl)methyl)isonicotinic acid. LCMS theoretical m/z = 602.3. [M+H]+, found 603.3. EXAMPLE 305, COMPOUND 285

[0940] N-(3-chloro-5-fluoro-2-((4-methylpiperazin-1-yl)methyl)isonicotinoyl)-O-((1s,3S)-3-(2-(5,6, 7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)-L-homoserine. The D2 isomer was used in General Scheme D-2 using General Procedure I with 3-chloro-5-fluoro-2-((4-methylpiperazin-1-yl)methyl)isonicotinic acid. LCMS theoretical m/z = 602.3. [M+H]+, found 603.3. EXAMPLE 306, COMPOUND 286

[0941] (S)-2-(pyrimidin-4-ylamino)-5-(3-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)propoxy)pentanoic acid. Prepared by modifying the reaction with intermediate 2i in Example 2 to replace 2-ethylbutanoic acid with 4-chloropyrimidine and sodium bicarbonate. LCMS theoretical m/z = 385.2. [M+H]+, found 386.2. EXAMPLE 307, COMPOUND 287

[0942] N-(3,5-dichloroisonicotinoyl)-O-(4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl)-L-homoserine. The F2 isomer was used in General Scheme F-2 using General Procedure I with 3,5-dichloroisonicotinic acid. LCMS theoretical m/z = 480.1. [M+H]+, found 481.1. EXAMPLE 308, COMPOUND 288

[0943] N-(3-chloro-5-methylisonicotinoyl)-O-(4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl)-L-homoserine. The F2 isomer was used in General Scheme F-2 using General Procedure I with 3-chloro-5-methylisonicotinic acid. LCMS theoretical m/z = 460.2. [M+H]+, found 461.2. EXAMPLE 309, COMPOUND 289

[0944] N-(2,4-dimethylnicotinoyl)-O-(4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl)-L-homoserine. The F2 isomer was used in General Scheme F-2 using General Procedure I with 2,4-dimethylnicotinic acid. LCMS theoretical m/z = 440.2. [M+H]+, found 441.2. EXAMPLE 310, COMPOUND 290

[0945] N-(4-cyano-2,6-dimethylbenzoyl)-O-(4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl)-L- homoserine. The F2 isomer was used in General Scheme F-2 using General Procedure I with 4-cyano-2,6-dimethylbenzoic acid. LCMS theoretical m/z = 464.2. [M+H]+, found 465.3. EXAMPLE 311, COMPOUND 291

[0946] N-(3,5-dichloroisonicotinoyl)-O-(4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl)-D-homoserine. The F1 isomer was used in General Scheme F-2 using General Procedure I with 3,5-dichloroisonicotinic acid. LCMS theoretical m/z = 480.1. [M+H]+, found 481.1. EXAMPLE 312, COMPOUND 292

[0947] N-(3-chloro-5-fluoroisonicotinoyl)-O-(4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl)-L-homoserine. The F2 isomer was used in General Scheme F-2 using General Procedure I with 3-chloro-5-fluoroisonicotinic acid. LCMS theoretical m/z = 464.2. [M+H]+, found 465.1. EXAMPLE 313, COMPOUND 293

[0948] N-((3R,5S)-3,5-dimethylmorpholine-4-carbonyl)-O-(4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl )butyl)-L-homoserine. The F2 isomer was used in General Scheme F-2 using General Procedure G with (3R,5S)-3,5-dimethylmorpholine. LCMS theoretical m/z = 448.3. [M+H]+, found 449.3. EXAMPLE 314, COMPOUND 294

[0949] N-(2,6-dichlorobenzoyl)-O-(4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl)-D-homoserine. The F1 isomer was used in General Scheme F-2 using General Procedure I with 2,6-dichlorobenzoic acid. LCMS theoretical m/z = 479.1. [M+H]+, found 480.1. EXAMPLE 315, COMPOUND 295

[0950] N-(2,6-dichlorobenzoyl)-O-(4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl)-L-homoserine. The F2 isomer was used in General Scheme F-2 using General Procedure I with 2,6-dichlorobenzoic acid. LCMS theoretical m/z = 479.1. [M+H]+, found 480.1. EXAMPLE 316, COMPOUND 296

[0951] N-(3,5-dimethylisonicotinoyl)-O-(4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl)-D-homoserine. The F1 isomer was used in General Scheme F-2 using General Procedure I with 3,5-dimethylisonicotinic acid. LCMS theoretical m/z = 440.2. [M+H]+, found 441.2. EXAMPLE 317, COMPOUND 297

[0952] N-(3,5-dimethylisonicotinoyl)-O-(4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl)-L-homoserine. The F2 isomer was used in General Scheme F-2 using General Procedure I with 3,5-dimethylisonicotinic acid. LCMS theoretical m/z = 440.2. [M+H]+, found 441.2. EXAMPLE 318, COMPOUND 298 The or

[0953] N-(2,4-dichloro-6-fluorobenzoyl)-O-(4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl)-L- homoserine. The F2 isomer was used in General Scheme F-2 using General Procedure I with 2,4-dichloro-6-fluorobenzoic acid. LCMS theoretical m/z = 497.1 [M+H]+, found 498.1. EXAMPLE 319, COMPOUND 299

[0954] N-(2,4-dimethyl-6-oxo-1,6-dihydropyridine-3-carbonyl)-O- (4-(5,6,7,8-tetrahydro-1,8 -naphthyridin-2-yl)butyl)-L-homoserine. The F2 isomer was used in General Scheme F-2 using General Procedure I with 2,4-dimethyl-6-oxo-1,6-dihydropyridine-3-carboxylic acid. LCMS theoretical m/z = 456.2. [M+H]+, found 457.2. EXAMPLE 320, COMPOUND 300

[0955] N-(3-chloro-5-methoxy-isonicotinoyl)-O-(4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl)-L- homoserine. The F2 isomer was used in General Scheme F-2 using General Procedure I with 3-chloro-5-methoxyisonicotinic acid. LCMS theoretical m/z = 476.2. [M+H]+, found 477.1. EXAMPLE 321, COMPOUND 301

[0956] N-(2-chloro-6-fluorobenzoyl)-O-(4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl)-L-homoserine. The F2 isomer was used in General Scheme F-2 using General Procedure I with 2-chloro-6-fluorobenzoic acid. LCMS theoretical m/z = 463.2. [M+H]+, found 464.2. EXAMPLE 322, COMPOUND 302

[0957] N-(tert-butoxycarbonyl)-O-(4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl)-L-homoserine. The F2 isomer was used in General Scheme F-2 using General Procedure No. Theoretical LCMS m/z = 421.2. [M+H]+, found 422.2. EXAMPLE 323, COMPOUND 303

[0958] N-(tert-butoxycarbonyl)-O-(4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl)-D-homoserine. The F1 isomer was used in General Scheme F-2 using General Procedure No. Theoretical LCMS m/z = 421.2. [M+H]+, found 422.2. EXAMPLE 324, COMPOUND 304

[0959] N-(5-bromo-2-hydroxy-isonicotinoyl)-O-(4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl)-L- homoserine. The F2 isomer was used in General Scheme F-2 using General Procedure I with 5-bromo-2-hydroxyisonicotinic acid. LCMS theoretical m/z = 506.1. [M+H]+, found 507.1. EXAMPLE 325, COMPOUND 305

[0960] N-(3-bromo-5-chloro-2-fluoroisonicotinoyl)-O-(4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl)- L-homoserine. The F2 isomer was used in General Scheme F-2 using General Procedure I with 3-bromo-5-chloro-2-fluoroisonicotinic acid. LCMS theoretical m/z = 542.1. [M+H]+, found 543.1. EXAMPLE 326, COMPOUND 306

[0961] N-(2,4-dimethyl-6-oxo-1-phenyl-1,6-dihydropyridine-3-carbonyl)-O-(4-(5,6,7,8-tetrahydro -1,8-naphthyridin-2-yl)butyl)-L- homoserine. The F2 isomer was used in General Scheme F-2 using General Procedure I with 2,4-dimethyl-6-oxo-1-phenyl-1,6-dihydropyridine-3-carboxylic acid. LCMS theoretical m/z = 532.3. [M+H]+, found 533.3. EXAMPLE 327, COMPOUND 307

[0962] O-(4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl)-N- (5,6,7,8-tetrahydronaphthylalene-1 -carbonyl)-L-homoserine. The F2 isomer was used in General Scheme F-2 using General Procedure I with 5,6,7,8-tetrahydronaphthalene-1-carboxylic acid. LCMS theoretical m/z = 465.3. [M+H]+, found 466.2. EXAMPLE 328, COMPOUND 308

[0963] N-(3-bromo-2,6-dimethylbenzoyl)-O-(4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl)-L- homoserine. The F2 isomer was used in General Scheme F-2 using General Procedure I with 3-bromo-2,6-dimethylbenzoic acid. LCMS theoretical m/z = 517.2. [M+H]+, found 518.2. EXAMPLE 329, COMPOUND 309

[0964] N-(3-chloro-5-fluoroisonicotinoyl)-O-(4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl)-D-homoserine. The F1 isomer was used in General Scheme F-2 using General Procedure I with 3-chloro-5-fluoroisonicotinic acid. LCMS theoretical m/z = 464.1. [M+H]+, found 465.1. EXAMPLE 330, COMPOUND 310

[0965] N-(3-bromo-2-chloro-6-fluorobenzoyl)-O-(4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl)- L-homoserine. The F2 isomer was used in General Scheme F-2 using General Procedure I with 3-bromo-2-chloro-6-fluorobenzoic acid. LCMS theoretical m/z = 541.1. [M+H]+, found 542.1. GENERAL SCHEME I

[0966] tert-butyl 7-(4-hydroxy-3-methylbutyl)-3,4-dihydro-1,8-naphthyridine-1(2H)-carboxylate (2I in Scheme I). To a solution of tert-butyl 7-(4-ethoxy-4-oxobutyl)-3,4-dihydro-1,8-naphthyridine-1(2H)-carboxylate (1I in Scheme I, 20 g, 57. 40 mmol) and Mel (8.15 g, 57.40 mmol) in THF (200 ml) KHMDS was added dropwise (1 M, 57.40 ml) under N2 at -78 °C and the resulting mixture was left to stir for 1 h at -78 °C. The mixture was then heated to 0°C and then to this was slowly added EtOAc (100 ml) followed by a saturated aqueous ammonium chloride solution (600 ml). The layers were separated and the aqueous layer was extracted with EtOAc. The combined organic extracts were dried over Na2SO4, filtered and concentrated in vacuo. The crude residue was purified by normal phase chromatography on silica gel to provide the title compound. Starting from the title compound, the remainder of the reactions in Scheme I were conducted analogously to the corresponding reactions in Scheme C/General Procedure C to provide the following five compounds. EXAMPLE 331, COMPOUND 311

[0967] N-(3-chloro-5-fluoroisonicotinoyl)-O-(2-methyl-4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl)homoserine . Prepared according to General Scheme I using General Procedure N with 3-chloro-5-fluoroisonicotinic acid in which the title compound was isolated from a racemic mixture. LCMS theoretical m/z = 478.1. [M+H]+, found 479.1. EXAMPLE 332, COMPOUND 312

[0968] N-(3-chloro-5-fluoroisonicotinoyl)-O-((R)-2-methyl-4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl )butyl)-D-homoserine. Prepared according to General Scheme I using General Procedure N with 3-chloro-5-fluoroisonicotinic acid to provide a racemic mixture. The title compound was isolated from the racemic mixture as the fourth eluting isomer by SFC. LCMS theoretical m/z = 478.1. [M+H]+, found 479.1. EXAMPLE 333, COMPOUND 313

[0969] N-(3-chloro-5-fluoroisonicotinoyl)-O-((S)-2-methyl-4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl )butyl)-L-homoserine. Prepared according to General Scheme I using General Procedure N with 3-chloro-5-fluoroisonicotinic acid to provide a racemic mixture. The title compound was isolated from the racemic mixture as the first eluting isomer by SFC. LCMS theoretical m/z = 478.1. [M+H]+, found 479.1. EXAMPLE 334, COMPOUND 314

[0970] N-(3-chloro-5-fluoroisonicotinoyl)-O-((R)-2-methyl-4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl )butyl)-L-homoserine. Prepared according to General Scheme I using General Procedure N with 3-chloro-5-fluoroisonicotinic acid to provide a racemic mixture. The title compound was isolated from the racemic mixture as the second elution isomer by SFC. LCMS theoretical m/z = 478.1. [M+H]+, found 479.1. EXAMPLE 335, COMPOUND 315

[0971] N-(3-chloro-5-fluoroisonicotinoyl)-O-((S)-2-methyl-4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl )butyl)-D-homoserine. Prepared according to General Scheme I using General Procedure N with 3-chloro-5-fluoroisonicotinic acid to provide a racemic mixture. The title compound was isolated from the racemic mixture as the third eluting isomer by SFC. LCMS theoretical m/z = 478.1. [M+H]+, found 479.1. EXAMPLE 336, COMPOUND 316

[0972] N-(3-chloro-5-methoxy-isonicotinoyl)-O-(2-methyl-4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl )homoserine. Prepared according to General Scheme I using General Procedure N with 3-chloro-5-methoxyisonicotinic acid to provide a racemic mixture. The title compound was isolated from the racemic mixture by reverse phase preparative HPLC. LCMS theoretical m/z = 490.2. [M+H]+, found 490.9. EXAMPLE 337, COMPOUND 317

[0973] N-(2,6-dichlorobenzoyl)-O-((S)-2-methyl-4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl )-L-homoserine. Prepared according to General Scheme I using General Procedure N with 2,6-dichlorobenzoic acid. The title compound was isolated as the first eluting isomer by SFC. LCMS theoretical m/z = 493.2. [M+H]+, found 494.2. EXAMPLE 338, COMPOUND 318

[0974] N-(2,6-dichlorobenzoyl)-O-((R)-2-methyl-4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl )-L-homoserine. Prepared according to General Scheme I using General Procedure N with 2,6-dichlorobenzoic acid. The title compound was isolated as the second eluting isomer by SFC. LCMS theoretical m/z = 493.2. [M+H]+, found 494.2. EXAMPLE 339, COMPOUND 319

[0975] N-(2,6-dichlorobenzoyl)-O-((S)-2-methyl-4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl )-D-homoserine. Prepared according to General Scheme I using General Procedure N with 2,6-dichlorobenzoic acid. The title compound was isolated as the third eluting isomer by SFC. LCMS theoretical m/z = 493.2. [M+H]+, found 494.2. EXAMPLE 340, COMPOUND 320

[0976] N-(2,6-dichlorobenzoyl)-O-((R)-2-methyl-4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl )-D-homoserine. Prepared according to General Scheme I using General Procedure N with 2,6-dichlorobenzoic acid. The title compound was isolated as the fourth eluting isomer by SFC. LCMS theoretical m/z = 493.2. [M+H]+, found 494.2. EXAMPLE 341, COMPOUND 321

[0977] N-(2-chloro-6-fluorobenzoyl)-O-((S)-2-methyl-4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl )butyl)-L-homoserine. Prepared according to General Scheme I using General Procedure N with 2-chloro-6-fluorobenzoic acid. The title compound was isolated as the first eluting isomer by SFC. LCMS theoretical m/z = 477.2 [M+H]+, found 478.1. EXAMPLE 342, COMPOUND 322

[0978] N-(2-chloro-6-fluorobenzoyl)-O-((R)-2-methyl-4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl )butyl)-L-homoserine. Prepared according to General Scheme I using General Procedure N with 2-chloro-6-fluorobenzoic acid. The title compound was isolated as the second eluting isomer by SFC. LCMS theoretical m/z = 477.2 [M+H]+, found 478.1. EXAMPLE 343, COMPOUND 323

[0979] N-(2-chloro-6-fluorobenzoyl)-O-((S)-2-methyl-4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl )butyl)-D-homoserine. Prepared according to General Scheme I using General Procedure N with 2-chloro-6-fluorobenzoic acid. The title compound was isolated as the third eluting isomer by SFC. LCMS theoretical m/z = 477.2 [M+H]+, found 478.1. EXAMPLE 344, COMPOUND 324

[0980] N-(2-chloro-6-fluorobenzoyl)-O-((R)-2-methyl-4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl )butyl)-D-homoserine. Prepared according to General Scheme I using General Procedure N with 2-chloro-6-fluorobenzoic acid. The title compound was isolated as the fourth eluting isomer by SFC. LCMS theoretical m/z = 477.2 [M+H]+, found 478.1. EXAMPLE 345, COMPOUND 325

[0981] N-(4-fluoro-2-methylnicotinoyl)-O-((S)-2-methyl-4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl )butyl)-L-homoserine. Prepared according to General Scheme I using General Procedure N with 4-fluoro-2-methylnicotinic acid. The title compound was isolated as the first eluting isomer by SFC. LCMS theoretical m/z = 458.2 [M+H]+, found 459.2. EXAMPLE 346, COMPOUND 326

[0982] N-(4-fluoro-2-methylnicotinoyl)-O-((R)-2-methyl-4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl )butyl)-L-homoserine. Prepared according to General Scheme I using General Procedure N with 4-fluoro-2-methylnicotinic acid. The title compound was isolated as the second eluting isomer by SFC. LCMS theoretical m/z = 458.2. [M+H]+, found 459.2. EXAMPLE 347, COMPOUND 327

[0983] N-(4-fluoro-2-methylnicotinoyl)-O-((S)-2-methyl-4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl )butyl)-D-homoserine. Prepared according to General Scheme I using General Procedure N with 4-fluoro-2-methylnicotinic acid. The title compound was isolated as the third eluting isomer by SFC. LCMS theoretical m/z = 458.2. [M+H]+, found 459.2. EXAMPLE 348, COMPOUND 328

[0984] N-(4-fluoro-2-methylnicotinoyl)-O-((R)-2-methyl-4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl )butyl)-D-homoserine. Prepared according to General Scheme I using General Procedure N with 4-fluoro-2-methylnicotinic acid. The title compound was isolated as the fourth eluting isomer by SFC. LCMS theoretical m/z = 458.2. [M+H]+, found 459.2. GENERAL SCHEME J

[0985] 2-(but-3-en-1-yl)-2-methyl-1,3-dioxolane. To a solution of hex-5-en-2-one (18 ml, 155 mmol) in toluene (155 ml) was added ethylene glycol (11.3 ml, 202 mmol) and p-toluenesulfonic acid monohydrate (2.96 g, 15.5 mmol)), and the resulting mixture was stirred at 110 °C overnight and was diluted with water and EtOAc. The layers were separated and the aqueous layer was extracted with EtOAc. The combined organic extracts were washed with brine, dried over Na2SO4, filtered and concentrated in vacuo to give the title compound which was used without further purification.

[0986] 2-methyl-2-(2-(oxiran-2-yl)ethyl)-1,3-dioxolane. To a solution of 2-(but-3-en-1-yl)-2-methyl-1,3-dioxolane (15.8 g, 111 mmol) in DCM (200 ml) was added m-chloroperoxybenzoic acid (23 g, 134 mmol), and the resulting mixture was stirred at room temperature overnight and was diluted with water and DCM. The layers were separated and the aqueous layer was extracted with DCM. The combined organic extracts were washed with brine, dried over Na2SO4, filtered and concentrated in vacuo to give the title compound which was used without further purification.

[0987] (S)-4-(2-methyl-1,3-dioxolan-2-yl)butane-1,2-diol. To a solution of 2-methyl-2-(2-(oxiran-2-yl)ethyl)-1,3-dioxolane (5.3 g, 33 mmol) in toluene (67 ml) was added (R,R) -(-)-N,N"-bis(3,5-ditertbutylsalicylidene)-1,2-cyclohexanediaminocobalt (II) (40.55 mg, 0.07 mmol), acetic acid (0.04 ml , 0.67 mmol) and water (0.33 ml, 18.5 mmol) and the resulting mixture was allowed to stir at room temperature overnight and then was concentrated in vacuo. The crude residue was purified by normal phase chromatography. on silica gel to provide the title compound.

[0988] (S)-1-(allyloxy)-4-(2-methyl-1,3-dioxolan-2-yl)butan-2-ol. A solution of (S)-4-(2-methyl-1,3-dioxolan-2-yl)butane-1,2-diol (1.8 g, 10.2 mmol) in THF (34 ml) was NaH (410 mg, 10.2 mmol) was added at 0 °C and the resulting mixture was stirred at room temperature. After 1 h, allyl bromide (0.9 ml, 10.2 mmol) was added and the resulting mixture was allowed to stir at room temperature overnight and was concentrated in vacuo. The crude residue was purified by normal phase chromatography on silica gel to provide the title compound.

[0989] (S)-((1-(allyloxy)-4-(2-methyl-1,3-dioxolan-2-yl)butan-2-yl)oxy)(tert-butyl)dimethylsilane. To a solution of (S)-1-(allyloxy)-4-(2-methyl-1,3-dioxolan-2-yl)butan-2-ol (1.00 g, 4.6 mmol) in CH2Cl2 ( 9 ml) imidazole (1.1 g, 16 mmol) and TBSCl (1.8 ml, 6.9 mmol) were added and the resulting mixture was allowed to stir at room temperature for 10 min. The reaction mixture was diluted with saturated sodium bicarbonate and CH2Cl2. The combined organic extracts were washed with brine, dried over Na2SO4, filtered and concentrated in vacuo. The crude residue was purified by normal phase chromatography on silica gel to provide the title compound.

[0990] (S)-2-(2-((tert-butyldimethylsilyl)oxy)-4-(2-methyl-1,3-dioxolan-2-yl)butoxy)acetaldehyde. To a solution of (S)-((1-(allyloxy)-4-(2-methyl-1,3-dioxolan-2-yl)butan-2-yl)oxy)(tert-butyl)dimethylsilane (1, 1 g, 2.4 mmol) in 3:1 THF/H2O (15 ml) were added NaIO4 (2.1 g, 9.7 mmol) and OsO4 (0.04 ml, 0.121 mmol) and the resulting mixture was allowed to stir at room temperature for 3 hours and was diluted with saturated sodium bicarbonate, saturated sodium thiosulfate and EtOAc. The layers were separated and the aqueous layer was extracted with EtOAc. The combined organic extracts were washed with brine, dried over Na2SO4, filtered and concentrated in vacuo to provide the title compound which was used without further purification.

[0991] (S,E)-2-((tert-butoxycarbonyl)amino)-4-(2-((tert-butyldimethylsilyl)oxy)-4-(2-methyl-1,3-dioxolan-2-yl )butoxy)methylbut-2-enoate. To a solution of (S)-2-(2-((tert-butyldimethylsilyl)oxy)-4-(2-methyl-1,3-dioxolan-2-yl)butoxy)acetaldehyde (1.1 mg, 2. 4 mmol) in CH2Cl2 (6 ml) was added methyl 2-((tert-butoxycarbonyl)amino)-2-(dimethoxyphosphoryl)acetate (718 mg, 5.3 mmol) and DBU (0.53 ml, 3.50 mmol) and the resulting mixture was allowed to stir at room temperature for 2 hours and then concentrated in vacuo. The crude residue was purified by normal phase column chromatography to provide the title compound.

[0992] (S,E)-2-((tert-butoxycarbonyl)amino)-4-((2-((tert-butyldimethylsilyl)oxy)-5-oxohexyl)oxy)methylbut-2-enoate . To a solution of (S,E)-2-((tert-butoxycarbonyl)amino)-4-(2-((tert-butyldimethylsilyl)oxy)-4-(2-methyl-1,3-dioxolan-2- methyl yl)butoxy)but-2-enoate (12.4 mg, 0.02 mmol) in 4:1 CH3CN/H2O (0.5 ml) was added DDQ (0.9 mg, 0.004 mmol) and to The resulting mixture was allowed to stir at room temperature for 2 hours and then concentrated in vacuo. The crude residue was purified by normal phase column chromatography to provide the title compound.

[0993] N-(tert-butoxycarbonyl)-O-((S)-2-((tert-butyldimethylsilyl)oxy)-5-oxohexyl)methyl homoserinate. To a solution of (S,E)-2-((tert-butoxycarbonyl)amino)-4-((2-((tert-butyldimethylsilyl)oxy)-5-oxohexyl)oxy)but-2-enoate methyl methyl (195 mg, 0.334 mmol) in MeOH (2 ml) Pd(OH)2/C (20% by weight on carbon, 20 mg) was added and the resulting mixture was stirred under an H2 atmosphere overnight and it was filtered through Celite, then concentrated in vacuo to give the title compound which required no further purification.

[0994] N-(tert-butoxycarbonyl)-O-((S)-2-((tert-butyldimethylsilyl)oxy)-4-(1,8-naphthyridin-2-yl)butyl)methyl homoserinate. To a solution of methyl N-(tert-butoxycarbonyl)-O-((S)-2-((tert-butyldimethylsilyl)oxy)-5-oxohexyl)homoserinate (200 mg, 0.341 mmol) in EtOH (1 ml) L-proline (27.5 mg, 0.239 mmol) and 2-aminonicotinaldehyde (83.4 mg, 0.683 mmol) were added and the resulting mixture was stirred at 75°C overnight and was then concentrated in vacuo. The crude residue was purified by normal phase column chromatography to provide the title compound.

[0995] N-(tert-butoxycarbonyl)-O-((S)-2-((tert-butyldimethylsilyl)oxy)-4-(1,8-naphthyridin-2-yl)butyl)methyl homoserinate. To a solution of N-(tert-butoxycarbonyl)-O-((S)-2-((tert-butyldimethylsilyl)oxy)-4-(1,8-naphthyridin-2-yl)butyl)methyl homoserinate (67 .1 mg, 0.10 mmol) in MeOH (2 ml) Pd(OH)2/C (20% by weight on carbon, 20 mg) was added and the resulting mixture was stirred under an atmosphere of H2 overnight and was filtered through Celite then concentrated in vacuo. The crude residue was purified by normal phase chromatography on silica gel to provide the title compound.

[0996] O-((S)-2-((tert-butyldimethylsilyl)oxy)-4-(1,8-naphthyridin-2-yl)butyl)methyl homoserinate. To a solution of N-(tert-butoxycarbonyl)-O-((S)-2-((tert-butyldimethylsilyl)oxy)-4-(1,8-naphthyridin-2-yl)butyl)methyl homoserinate (35 .0 mg, 0.052 mmol) in DCM (0.1 ml) was added 4N HCl in 1,4-dioxane (0.06 ml, 0.207 mmol) and the resulting mixture was allowed to stir at room temperature overnight , then was concentrated in vacuo to give the title compound which was used without further purification.

[0997] N-(3-chloro-5-fluoroisonicotinoyl)-O-((S)-2-hydroxy-4-(1,8-naphthyridin-2-yl)butyl)methyl homoserinate. To a solution of 4-[(2S)- 2-[tert-butyl(diphenyl)silyl]oxy-4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butoxy Methyl ]-2-[(3-chloro-5-fluoro-pyridine-4-carbonyl)amino]butanoate (38.0 mg, 0.0518 mmol) in THF (0.1 ml) was added tetrabutylammonium fluoride ( 0.06 ml, 0.0622 mmol) and the resulting mixture was allowed to stir at room temperature for 2 hours and was diluted with saturated NH4Cl. The layers were separated and the aqueous layer was extracted with CH2Cl2. The combined organic extracts were washed with brine, dried over Na2SO4, filtered and concentrated in vacuo to provide the title compound which was used without further purification. EXAMPLE 349, COMPOUND 329

[0998] N-(3-chloro-5-fluoroisonicotinoyl)-O-((S)-2-hydroxy-4-(1,8-naphthyridin-2-yl)butyl)homoserine. To a solution of N-(3-chloro-5-fluoroisonicotinoyl)-O-((S)-2-hydroxy-4-(1,8-naphthyridin-2-yl)butyl)methyl homoserinate (25.6 mg , 0.0518 mmol) in THF/MeOH/H2O 3:1:1 LiOH (9.9 mg, 0.41 mmol) was added and the resulting mixture was allowed to stir at room temperature for 4 hours. LCMS showed conversion to product and the reaction mixture was diluted with water and purified by reverse phase preparative HPLC to provide N-(3-chloro-5-fluoroisonicotinoyl)-O-((S)-2-hydroxy-4-( 1,8-naphthyridin-2-yl)butyl)homoserine as a salt of TFA.

BIOLOGICAL EXAMPLES

[0999] N-(3-chloro-5-fluoroisonicotinoyl)-O-((S)-2-hydroxy-4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl )butyl)homoserine. (Compound 329, alternative preparation) Prepared according to General Scheme J using General Procedure I with 3-chloro-5-fluoroisonicotinic acid and General Procedure N. The mixture was neutralized with AcOH and then purified by preparative reversed-phase HPLC for the title compound as a salt of trifluoroacetic acid. LCMS theoretical m/z = 480.2. [M+H]+, found 481.1. EXAMPLE 350, COMPOUND 10

[1000] (S)-2-(1-Methyl-1H-indazol-4-carboxamido)-5-(3-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-) acid il)propoxy)pentanoic acid. Prepared according to Example 2, with the exception that the acid was replaced by 1-methyl-1H-indazole-4-carboxylic acid in the reaction with intermediate 2i. LCMS theoretical m/z = 465.2. [M+H]+, found 466.1. EXAMPLE 351, COMPOUND 11

[1001] (S)-2-(3-(1-methyl-1H-pyrazol-4-yl)benzamido)-5-(3-(5,6,7,8-tetrahydro-1,8) acid -naphthyridin-2-yl)propoxy)pentanoic acid. Prepared according to Example 2, with the exception that the acid was replaced by 3-(1-methyl-1H-pyrazol-4-yl)benzoic acid in the reaction with intermediate 2i. LCMS theoretical m/z = 491.2. [M+H]+, found 492.2. EXAMPLE 352, COMPOUND 12

[1002] (S)-2-(2-chloro-3-fluorobenzamido)-6-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethoxy acid) hexanoic. Prepared according to Example 2, with the exception that the bromide was replaced by 6-bromohex-1-ene in the reaction with intermediate 2d and the acid was replaced by 2-chloro-3-fluorobenzoic acid in the reaction with intermediate 2i. LCMS theoretical m/z = 463.2. [M+H]+, found 464.1. EXAMPLE 353, COMPOUND 13

[1003] (S)-2-(3-(1-methyl-1H-pyrazol-4-yl)benzamido)-6-(2-(5,6,7,8-tetrahydro-1,8) acid -naphthyridin-2-yl))ethoxy)hexanoic. Prepared according to Example 2, with the exception that the bromide was replaced by 6-bromohex-1-ene in the reaction with intermediate 2d and the acid was replaced by 3-(1-methyl-1H-pyrazol-4- il)benzoic acid in the reaction with intermediate 2i. LCMS theoretical m/z = 491.2. [M+H]+, found 492.2. EXAMPLE 354, COMPOUND 16

[1004] (S)-2-(2-ethylbutanamido)-6-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethoxy)hexanoic acid. Prepared according to Example 2, with the exception that the bromide was replaced by 6-bromohex-1-ene in the reaction with intermediate 2d and the acid was replaced by 2-ethylbutanoic acid in the reaction with intermediate 2i. LCMS theoretical m/z = 405.2. [M+H]+, found 406.2. EXAMPLE 355, COMPOUND 17

[1005] (S)-2-(1-Methyl-1H-indazol-4-carboxamido)-6-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-) acid il)ethoxy)hexanoic. Prepared according to Example 2, with the exception that the bromide was replaced by 6-bromohex-1-ene in the reaction with intermediate 2d and the acid was replaced by 1-methyl-1H-indazole-4-carboxylic acid in the reaction with 2i intermediate. LCMS theoretical m/z = 465.2. [M+H]+, found 466.2. EXAMPLE 356, COMPOUND 20

[1006] (S)-2-((tert-butoxycarbonyl)amino)-5-(3-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)propoxy)pentanoic acid . Prepared according to Example 2, with the exception that the acid was replaced by di-tert-butyl dicarbonate in the reaction with intermediate 2i. LCMS theoretical m/z = 407.2. [M+H]+, found 408.2. EXAMPLE 357, COMPOUND 21

[1007] N-benzoyl-O-((1s,3r)-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine. The D2 isomer was used in General Scheme D-2 using General Procedure I with benzoic acid. LCMS theoretical m/z = 437.2. [M+H]+, found 438.8. EXAMPLE 358, COMPOUND 178

[1008] N-(quinazolin-4-yl)-O-((1r,3s)-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl) ethyl)cyclobutyl)homoserine. The E2 isomer was used in General Scheme E-2 using General Procedure E with 4-chloroquinazoline. LCMS theoretical m/z = 461.2. [M+H]+, found 462.3. EXAMPLE 359, COMPOUND 179

[1009] N-(8-fluoroquinazolin-4-yl)-O-((1s,3r)-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2- yl)ethyl)cyclobutyl)homoserine. The E2 isomer was used in General Scheme E-2 using General Procedure E with 4-chloro-8-fluoroquinazoline. LCMS theoretical m/z = 479.2. [M+H]+, found 480.2. EXAMPLE 360, COMPOUND 180

[1010] N-(7-fluoroquinazolin-4-yl)-O-((1s,3r)-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2- yl)ethyl)cyclobutyl)homoserine. The E2 isomer was used in General Scheme E-2 using General Procedure E with 4-chloro-7-fluoroquinazoline. LCMS theoretical m/z = 479.2. [M+H]+, found 480.2. EXAMPLE 361, COMPOUND 181

[1011] N-(7-methylquinazolin-4-yl)-O-((1s,3r)-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2- yl)ethyl)cyclobutyl)homoserine. The E2 isomer was used in General Scheme E-2 using General Procedure E with 4-chloro-7-methylquinazoline. LCMS theoretical m/z = 475.3. [M+H]+, found 476.3. EXAMPLE 362, COMPOUND 182

[1012] N-(6-fluoroquinazolin-4-yl)-O-((1s,3r)-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2- yl)ethyl)cyclobutyl)homoserine. The E2 isomer was used in General Scheme E-2 using General Procedure E with 4-chloro-6-fluoroquinazoline. LCMS theoretical m/z = 479.2. [M+H]+, found 480.2. EXAMPLE 363, COMPOUND 183

[1013] N-(5-fluoroquinazolin-4-yl)-O-((1s,3r)-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2- yl)ethyl)cyclobutyl)homoserine. The E2 isomer was used in General Scheme E-2 using General Procedure E with 4-chloro-5-fluoroquinazoline. LCMS theoretical m/z = 479.2. [M+H]+, found 480.2. EXAMPLE 364, COMPOUND 184

[1014] N-(6-methylquinazolin-4-yl)-O-((1s,3r)-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2- yl)ethyl)cyclobutyl)homoserine. The E2 isomer was used in General Scheme E-2 using General Procedure E with 4-chloro-6-methylquinazoline. LCMS theoretical m/z = 475.3. [M+H]+, found 476.3. EXAMPLE 365, COMPOUND 185

[1015] N-(6-(tert-butyl)-2-phenylpyrimidin-4-yl)-O-((1s,3S)-3-(2- (5,6,7,8-tetrahydro- 1,8-naphthyridin-2-yl)ethyl)cyclobutyl)-L-homoserine. The E2 isomer was used in General Scheme E-2 using General Procedure E with 4-(tert-butyl)-6-chloro-2-phenylpyrimidine. LCMS theoretical m/z = 543.3. [M+H]+, found 544.3. EXAMPLE 366, COMPOUND 23

[1016] (S)-2-((tert-butoxycarbonyl)amino)-6-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethoxy)hexanoic acid . It was prepared by the same procedure used to prepare Example 2, with the exception that the bromide was replaced by 6-bromohex-1-ene in the reaction with intermediate 2d and the acid was replaced by di-tert-butyl dicarbonate in the reaction with 2i intermediate. LCMS theoretical m/z = 407.2. [M+H]+, found 408.2.

EXAMPLE B1- PROXIMITY-BASED INTEGRIN RECEPTOR BINDING ASSAY TO DETERMINE INHIBITOR POTENCY

[1017] The biochemical potency of the compounds was determined using a proximity-based assay (ALPHASCREEN®, Perkin Elmer, Waltham, MA) as previously described (Ullman EF et al., Luminescent oxygen channeling immunoassay: Measurement of particle binding kinetics by chemiluminescence. Proc. Natl. Sci. USA, Vol. 91, pp. 5,426 to 5,430. To evaluate the potency of binding inhibitors to human αvβ6 integrin, inhibitory compounds and integrin were incubated together with TGFβ1 LAP and biotinylated anti-LAP antibody plus acceptor and donor microspheres, following the manufacturer's recommendations. Donor microspheres were coated with streptavidin. The acceptor microspheres had a Nitrilotriacetic acid Ni chelator for binding to a 6xHis tag on human αvβ6 integrin. All incubations occurred at room temperature in 50 mM Tris-HCl, pH 7.5, 0.1% BSA supplemented with CaCl2 and 1 mM MgCl2 each.

[1018] The order of addition of the reagent was as follows:

[1019] 1. Alpha-v-beta-6 integrin, test inhibitor compound, LAP, biotinylated anti-LAP antibody and acceptor microspheres were all added together.

[1020] 2. After 2 hours, donor microspheres were added. After another 30 minute incubation, the samples were then read.

[1021] Integrin binding was assessed by exciting donor microspheres at 680 nm and measuring the fluorescent signal produced, between 520 to 620 nm, using a SynergyNeo2 multimode plate reader from Biotek Instruments (Winooski, VT, USA). Compound potency was assessed by determining the inhibitor concentrations required to reduce fluorescent light output by 50%. Data analysis for IC50 determinations was performed by nonlinear four-parameter logistic regression analysis using Dotmatics ELN software (Núcleo Informatics Inc., Branford, CT). IC50 values for the compounds in the Examples are given below in Table B-1 in ranges: below 50 nM; from above 50 nM to 250 nM; from above 250 nM to 1,000 nM; and above 1,000 nM. 1 the first elution compound of the referenced general synthetic scheme was tested 2 * the second elution compound of the referenced general synthetic scheme was tested the first elution compound of the last chromatography step described in the example was tested tt the second elution compound of the last chromatography step described in the example was tested

EXAMPLE B2- OTHER COMPOUNDS POTENTIALLY INHIBIT AVB6 IN A PROXIMITY-BASED ASSAY

[1022] The biochemical potency of compounds to inhibit αvβ6 integrin was determined for a second series of compounds using a proximity-based assay (ALPHASCREEN®, Perkin Elmer, Waltham, MA) as previously described (Ullman EF et al., Luminescent oxygen channeling immunoassay: Measurement of particle binding kinetics by chemiluminescence. Proc. Sci. USA, Vol. 91, pp. To evaluate the potency of inhibitors binding to human αvβ6 integrin, inhibitor and integrin compounds were incubated together with TGFβ1 LAP and biotinylated anti-LAP antibody plus acceptor and donor microspheres, following the manufacturer's recommendations. Donor microspheres were coated with streptavidin. The acceptor microspheres had a Nitrilotriacetic acid Ni chelator for binding to a 6xHis tag on human «vβe integrin. All incubations occurred at room temperature in 50 mM Tris-HCl, pH 7.5, 0.1% BSA supplemented with CaCl2 and 1 mM MgCl2 each.

[1023] The order of addition of the reagent was as follows:

[1024] 1. Alpha-v-beta-6 integrin, test inhibitor compound, LAP, biotinylated anti-LAP antibody and acceptor microspheres were all added together.

[1025] 2. After 2 hours, donor microspheres were added. After another 30 minute incubation, the samples were then read.

[1026] Integrin binding was assessed by exciting donor microspheres at 680 nm and measuring the fluorescent signal produced, between 520 to 620 nm, using a SynergyNeo2 multimode plate reader from Biotek Instruments (Winooski, VT, USA). Compound potency was assessed by determining the inhibitor concentrations required to reduce fluorescent light output by 50%. Data analysis for IC50 determinations was performed by nonlinear four-parameter logistic regression analysis using Dotmatics ELN software (Núcleo Informatics Inc., Branford, CT).

[1027] Example B3- Compounds potentially inhibit αvβi in a proximity-based assay The biochemical potency of compounds to inhibit αvβ1 integrin was determined using a proximity-based assay (ALPHASCREEN®, Perkin Elmer, Waltham, MA) as previously described (Ullman EF et al., Luminescent oxygen channeling immunoassay: Measurement of particle binding kinetics by chemiluminescence. To evaluate the potency of binding inhibitors to human vβe integrin, inhibitory compounds and integrin were incubated together with TGFβ1 LAP and biotinylated anti-LAP antibody plus acceptor and donor microspheres, following the manufacturer's recommendations. Donor microspheres were coated with streptavidin. The acceptor microspheres had a Nitrilotriacetic acid Ni chelator for binding to a 6xHis tag on human αvβi integrin. All incubations occurred at room temperature in 50 mM Tris-HCl, pH 7.5, 0.1% BSA supplemented with CaCl2 and 1 mM MgCl2 each.

[1028] The order of addition of the reagent was as follows:

[1029] 1. Alpha-v-beta-1 integrin, test inhibitor compound, LAP, biotinylated anti-LAP antibody and acceptor beads were all added together.

[1030] 2. After 2 hours, donor microspheres were added. After another 30 minute incubation, the samples were then read.

[1031] Integrin binding was assessed by exciting donor microspheres at 680 nm and measuring the fluorescent signal produced, between 520 to 620 nm, using a SynergyNeo2 multimode plate reader from Biotek Instruments (Winooski, VT, USA). Compound potency was assessed by determining the inhibitor concentrations required to reduce fluorescent light output by 50%. Data analysis for IC50 determinations was performed by nonlinear four-parameter logistic regression analysis using Dotmatics ELN software (Núcleo Informatics Inc., Branford, CT). IC50 values for the compounds in the Examples are provided in Figure 2, Table B-2 in ranges: 50 nM and below; from above 50 nM to 250 nM; from above 250 nM to 1,000 nM; and above 1,000 nM.

COMBINED INHIBITION RESULTS OF EXAMPLES Bi, B2 AND B3

[1032] Table B2, Figure 2, shows the IC50 data of the Examples

[1033] B2 and B3 for inhibition of integrin αvβi and αvβ6 in solid phase assays and inhibition of human integrin αvβi and αvβ6 in ALPHASCREEN® proximity-based assays. IC50 data is presented in four ranges: below 50 nM; from 50 nM to less than 250 nM; from above 250 nM to below 1,000 nM; and 1,000 nM and above.

Claims (13)

1. Compound, characterized by the fact that it presents Formula (I): or a salt thereof, in which: R1 is 5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl optionally substituted by R4, 1,2,3,4-tetrahydro-1, 8-naphthyridin-2-yl optionally substituted by R4, 6-aminopyridin-2-yl optionally substituted by R4, or (pyridin-2-yl)amino optionally substituted by R4; G is -C(O)R2or R3; R2 is C1-C6 alkyl optionally substituted by R2a, C3-C8 cycloalkyl optionally substituted by R2b, 3- to 12-membered heterocyclyl optionally substituted by R2c, C6-C14 aryl optionally substituted by R2d, 5- to 10-membered heteroaryl optionally substituted by R2e, -OR2for -NR2gR2h; R3 is C1-C6 alkyl optionally substituted by R3a, C3-C8 cycloalkyl optionally substituted by R3b, 3- to 12-membered heterocyclyl optionally substituted by R3c, C6-C14 aryl optionally substituted by R3, or 5- to 10-membered heteroaryl optionally substituted by R3e; L1 is C2-C4 alkylene optionally substituted by R4; L2 is a bond or C1-C3 alkylene optionally substituted by R4; L3 is C2-C4 alkylene optionally substituted by R4; Y is a bond or C3-C5 cycloalkylene optionally substituted by Ya; R2 is C1-C6 alkyl, C3-C8 cycloalkyl, 3- to 12-membered heterocyclyl, C6-C14 aryl or 5- to 10-membered heteroaryl, wherein C1-C6 alkyl, C3-C8 cycloalkyl, 3- to 12-membered heterocyclyl, C6-C14 aryl and 5- to 10-membered heteroaryl of R2f are optionally independently substituted by R2i; R2g and R2h are each independently hydrogen, deuterium, C1-C6 alkyl, C3-C8 cycloalkyl, 3- to 12-membered heterocyclyl, C6-C14 aryl, or 5- to 10-membered heteroaryl, wherein the C1-C6 alkyl, C3- C8 cycloalkyl, 3- to 12-membered heterocyclyl, C6-C14 aryl and 5- to 10-membered heteroaryl of R2g and R2h are optionally independently substituted by R2j; each R2a, R2b, R2c, R2d, R2e, R2i, R2j, R3a, R3b, R3c, R3d, R3ee Ya is independently oxo or R4; each R4 is independently deuterium, halogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C8 cycloalkyl, 3- to 12-membered heterocyclyl, C6-C14 aryl, 5- to 10-membered heteroaryl, -CN, - OR5, - SR5, -NR6R7, -NO2, -C=NH(OR5), -C(O)R5, -OC(O)R5, -C(O)OR5, -C(O) NR6R7, -NR5C( O)R6, -NR5C(O)OR6, -NR5C(O)NR6R7, -S(O)R5, -S(O)2R 5, -NR5S(O)R6, -NR5S(O)2R6, -S( O)NR6R7, -S(O)2NR6R7 or -P(O)(OR5)(OR6), where C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C8 cycloalkyl, heterocyclyl from 3 to 12 membered, C6-C14 aryl, 5 to 10 membered heteroaryl of R4 are optionally independently substituted by R4a; each R4a is independently deuterium, halogen, oxo, -OR8, -NR8R9, -C(O)R8, C(O)OR8, -NR8C(O)OR10, -CN, -S(O)R8, -S(O) 2R8, -P(O)(OR8)(OR9), C3-C8 cycloalkyl, 3- to 12-membered heterocyclyl, 5- to 10-membered heteroaryl, C6-C14 aryl or C1-C6 alkyl, wherein the 3- to 12 membered, 5 to 10 membered heteroaryl, C6-C14 aryl and C1-C6 alkyl of R4asion, independently, optionally substituted by R4b; each R4 is independently deuterium, oxo, -OH, -O(2H), halogen, or C1-C6 alkyl optionally substituted by deuterium, halogen, -OH, -O(2H) or oxo; each R5 is independently hydrogen, deuterium, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C6-C14 aryl, 5- to 10-membered heteroaryl, or 3- to 10-membered heterocyclyl, wherein the C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C6-C14 aryl, 5- to 10-membered heteroaryl, and 3- to 10-membered heterocyclyl of R5 are each optionally substituted independent by R5a; each R5a is independently halogen, deuterium, oxo, -CN, -OR10, -NR11R12, -P(O)(OR11)(OR12), 3- to 12-membered heterocyclyl, or C1-C6 alkyl optionally substituted by deuterium, halogen, -OH, -O(2H) or oxo; each R6 is independently hydrogen, deuterium, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C6-C14 aryl, 5- to 10-membered heteroaryl, or 3- to 6-membered heterocyclyl, wherein the C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C6-C14 aryl, 5- to 10-membered heteroaryl, and 3- to 6-membered heterocyclyl of R6 are optionally independently substituted by deuterium, halogen, oxo, -CN, -OR10, -NR11R12, or C1-C6 alkyl optionally substituted by deuterium, halogen, -OH, -O(2H) or oxo; each R7 is independently hydrogen, deuterium, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C6-C14 aryl, 5- to 10-membered heteroaryl, or 3- to 6-membered heterocyclyl, wherein the C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C6-C14 aryl, 5- to 10-membered heteroaryl, and 3- to 6-membered heterocyclyl of R7 are optionally independently substituted by deuterium, halogen, oxo, -CN, -OR10, -NR11R12, or C1-C6 alkyl optionally substituted by deuterium, halogen, -OH, -O(2H) or oxo; or R6 and R7 are taken together with the atom to which they are bonded to form a 3 to 10 membered heterocyclyl optionally substituted by deuterium, halogen, oxo, -OR10, -NR11R12or C1-C6 alkyl optionally substituted by deuterium, halogen, oxo, - OH or -O(2H); each R8 is independently hydrogen, deuterium, C1-C6 alkyl optionally substituted by deuterium, halogen or oxo, C2-C6 alkenyl optionally substituted by deuterium, halogen or oxo, or C2-C6 alkynyl optionally substituted by deuterium, halogen or oxo; each R9 is independently hydrogen, deuterium, C1-C6 alkyl optionally substituted by deuterium, halogen or oxo, C2-C6 alkenyl optionally substituted by deuterium, halogen or oxo, or C2-C6 alkynyl optionally substituted by deuterium, halogen or oxo; each R10 is independently hydrogen, deuterium, C1-C6 alkyl optionally substituted by deuterium, halogen or oxo, C2-C6 alkenyl optionally substituted by deuterium, halogen or oxo, or C2-C6 alkynyl optionally substituted by deuterium, halogen or oxo; each R11 is independently hydrogen, deuterium, C1-C6 alkyl optionally substituted by deuterium, halogen or oxo, C2-C6 alkenyl optionally substituted by deuterium, halogen or oxo, or C2-C6 alkynyl optionally substituted by deuterium, halogen or oxo; and each R12 is independently hydrogen, deuterium, C1-C6 alkyl optionally substituted by deuterium, halogen or oxo, C2-C6 alkenyl optionally substituted by deuterium, halogen or oxo, or C2-C6 alkynyl optionally substituted by deuterium, halogen or oxo; or R11 and R12 are taken together with the atom to which they are bonded to form a 3 to 6 membered heterocyclyl optionally substituted by deuterium, halogen, oxo or C1-C6 alkyl optionally substituted by deuterium, oxo or halogen. 2. Compound, characterized by the fact that it is selected from one of: Compound Nos. 1 to 209 in Table 1, or a salt thereof; Compound Nos. 210 to 329 in Table 2, or a salt thereof; or Compound Nos. 1 to 329 in Tables 1 and 2. 3. Compound, characterized by the fact that it is selected from the group consisting of: N-(2-chloro-3-fluorobenzoyl)-O-(4-(5,6,7,8-tetrahydro-1 ,8-naphthyridin-2-yl)butyl)homoserine; N-(1-methyl-1H-indazol-4-carbonyl)-O-(4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl)homoserine; N-(4,4-difluorocyclohexane-1-carbonyl)-O-(4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl)homoserine; N-pentanoyl-O-(4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl)homoserine; N-(3-fluoro-5-(trifluoromethyl)benzoyl)-O-(4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl)homoserine; N-(3-fluoro-5-(trifluoromethyl)benzoyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl) homoserine; N-pentanoyl-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine; N-(tert-butoxycarbonyl)-O-(4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl)homoserine; N-(4-fluorobenzoyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine; N-(4-chlorobenzoyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine; N-(3-fluorobenzoyl)- O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine; N-(3-chlorobenzoyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine; N-(2-chlorobenzoyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine; N-(2-fluorobenzoyl)- O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine; N-(2,3-difluorobenzoyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine; N-(2,4-difluorobenzoyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine; N-(2-chloro-4-fluorobenzoyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine; N-(3-chloro-5-fluorobenzoyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine; N-(3-chloro-2-fluorobenzoyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine; N-(3,5-difluorobenzoyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine; N-(2,3-dichlorobenzoyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine; N-(2-chloro-6-fluorobenzoyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine; N-(2,6-difluorobenzoyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine; N-(2,5-difluorobenzoyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine; N-(3,4-dichlorobenzoyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine; N-picolinoyl-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine; N-nicotinoyl-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine; N-(1-methyl-1H-indazol-4-carbonyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl )homoserine; N-(2-methyl-2H-indazol-6-carbonyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl )homoserine; N-(2-methyl-2H-indazol-5-carbonyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl )homoserine; N-(1-methyl-1H-pyrrolo[2,3-b]pyridine-4-carbonyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin -2- yl)ethyl)cyclobutyl)homoserine; N-(2-ethylbutanoyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine; N-(1-methyl-1H-pyrrolo[2,3-b]pyridine-5-carbonyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin -2-yl)ethyl)cyclobutyl)homoserine; N-(3-(hydroxymethyl)benzoyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine; N-(quinoline-5-carbonyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine; N-(2-cyclopropylbenzoyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine; N-(quinoline-7-carbonyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine; N-(quinoline-6-carbonyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine; N-(quinoline-8-carbonyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine; N-(3-cyclopropylbenzoyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine; N-(4-cyclopropylbenzoyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine; N-isonicotinoyl-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)-homoserine; N-(3-ethylpentanoyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)-homoserine; N-(2-chloro-3-fluorobenzoyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine; N-(3,4-difluorobenzoyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine; N-(3-ethylpentanoyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine; N-isonicotinoyl-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine; O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)-N-(3-(thiazol-5-yl)benzoyl) homoserine; N-(3-hydroxy-2-phenylquinolinayl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine; N-(3-(1-methyl-1H-pyrazol-4-yl)benzoyl)-O-(3-(4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2- yl)butyl)cyclobutyl)homoserine; N-(3-(1-methyl-1H-pyrazol-4-yl)benzoyl)-O-(4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl )homoserine; N-(2-hydroxy-2-phenylacetyl)-O-(4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl)homoserine; N-(2-hydroxy-2-phenylacetyl)-O-(4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl)-homoserine; N-(2-hydroxy-2-phenylacetyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine; N-(1-phenylcyclopropane-1-carbonyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine; N-(2-methyl-2-phenylquinolinayl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine; N-(1-phenylcyclobutane-1-carbonyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine; N-(2,2-dimethyl-3-phenylquinolinayl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine ; N-(tert-butoxycarbonyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine; N-(2-(4-fluorophenyl)-2-methylquinolinayl)-O- (3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl )homoserine; N-(3-methylaxethane-3-carbonyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine; N-(3-hydroxy-2,2-dimethylquinolinayl)-O-(3-(2- (5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine ; N-(3-methoxy-2,2-dimethylquinolinayl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine ; N-(2-methyl-2-(pyridin-3-yl)quinolinayl)-O- (3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl) ethyl)cyclobutyl)homoserine; N-(2,3-dihydro-1H-indene-2-carbonyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl )ethyl)cyclobutyl)homoserine; N-(3-cyano-2,2-dimethylquinolinayl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine ; N-pivaloyl-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine; N-(2,3-dihydro-1H-indene-1-carbonyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl )ethyl)cyclobutyl)homoserine; N-((neopentyloxy)carbonyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine; N-((1-methylcyclopropoxy)carbonyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine; N-((1-methylcyclobutoxy)carbonyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine; O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)-N-(((1,1,1-trifluoro-2 -methylpropan-2-yl)oxy)carbonyl)homoserine; N-(isopropoxycarbonyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine; N-(diethylcarbamoyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine; N-(tert-butylcarbamoyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine; N-(tert-butyl(methyl)carbamoyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine; N-(isopropyl(methyl)carbamoyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine; N-(diisopropylcarbamoyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine; N-(3,3-dimethylbutanoyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine; N-(3-methylbutanoyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine; N-(2-cyclobutylacetyl)- O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine; N-(2-(1-methylcyclopropyl)acetyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine; N-(2-cyclopropylacetyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine; N-(((1-(tert-butoxycarbonyl)-3-methylazetidin-3-yl)oxy)carbonyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8 -naphthyridin-2-yl)ethyl)cyclobutyl)homoserine; N-(((3-methyl-1-(methylsulfonyl)azetidin-3-yl)oxy)carbonyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8- naphthyridin-2-yl)ethyl)cyclobutyl)homoserine; N-(((1-acetyl-3-methylazetidin-3-yl)oxy)carbonyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2 - yl)ethyl)cyclobutyl)homoserine; N-(((3-methylazetidin-3-yl)oxy)carbonyl)-O-(3- (2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl )cyclobutyl)homoserine; N-((cyclohexyloxy)carbonyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine; N-(isobutoxycarbonyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine; N-(((pyrrolidin-3- yl)oxy)carbonyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2- yl)ethyl)cyclobutyl )homoserine; N-(4-(methylsulfonyl)butanoyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine; N-(((1- (methylsulfonyl)pyrrolidin-3-yl)oxy)carbonyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2- yl)ethyl)cyclobutyl)homoserine; N-(((1-(tert-butoxycarbonyl)pyrrolidin-3-yl)oxy)carbonyl)-O-(3-(2-(5,6,7,8-tetrahydro- 1,8-naphthyridin- 2-yl)ethyl)cyclobutyl)homoserine; N-(((1-acetylpyrrolidin-3- yl)oxy)carbonyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2- yl)ethyl )cyclobutyl)homoserine; N-((1-phenylethoxy)carbonyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine; N-((2-phenylcyclobutoxy)carbonyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine; N-((3-phenylcyclobutoxy)carbonyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine; 2-((tert-butoxycarbonyl)amino)-3-methyl-4-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutoxy acid )butanoic; N-(((2-phenylcyclohexyl)oxy)carbonyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl )homoserine; N-(((1-(tert-butoxycarbonyl)azetidin-3-yl)oxy)carbonyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin- 2-yl)ethyl)cyclobutyl)homoserine; N-(((4-phenylcyclohexyl)oxy)carbonyl)-O-(3-(2- (5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl )homoserine; N-(((1-acetylazetidin-3-yl)oxy)carbonyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl )cyclobutyl)homoserine; N-(((1-((tert-butoxycarbonyl)amino)propan-2-yl)oxy)carbonyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8 -naphthyridin-2-yl)ethyl)cyclobutyl)homoserine; N-(((1-acetamidopropan-2-yl)oxy)carbonyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl )cyclobutyl)homoserine; N-(((2-(3,5-dimethyl-1H-pyrazol- 1-yl)cyclopentyl)oxy)carbonyl)-O-(3-(2-(5,6,7,8-tetrahydro- 1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine; N-(((2-(3,5-dimethyl-1H-pyrazol-1-yl)cyclohexyl)oxy)carbonyl)-O-(3-(2-(5,6,7,8-tetra- hydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)-homoserine; N-(((1-(tert-butoxycarbonyl)-3-(3-chlorophenyl)azetidin-3-yl)oxy)carbonyl)-O-(3-(2-(5,6,7,8-tetra- hydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine; N-(((1-(tert-butoxycarbonyl)-3-(4-isopropylphenyl)azetidin-3-yl)oxy)carbonyl)-O-(3-(2-(5,6,7,8-tetra- hydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine; N-(((1-(tert-butoxycarbonyl)- 3-(phenylethynyl)azetidin-3-yl)oxy)carbonyl)-O-(3-(2-(5,6,7,8-tetrahydro- 1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine; N-(1-(tert-butoxycarbonyl)piperidine-4-carbonyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl) cyclobutyl)homoserine; N-(3,3-difluorocyclohexane-1-carbonyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl )homoserine; N-(2-ethyl-4,4-difluorobutanoyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)- homoserine; N-(((2-(phenylethynyl)cyclohexyl)oxy)carbonyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl) ethyl)cyclobutyl)-homoserine; N-(2-cyclohexyl-2-methylpropanoyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine ; N-(2-(pyridin-2-yl)benzoyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl) homoserine; N-(2-ethyl-4,4,4-trifluorobutanoyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl )homoserine; N-(2-morpholinobenzoyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine; N-(2-ethyl-2-phenylbutanoyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine; N-(1H-pyrrolo[3,2-b]pyridine-7-carbonyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl )ethyl)cyclobutyl)homoserine; N-(4-cyanotetrahydro-2H-pyran-4-carbonyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl )cyclobutyl)homoserine; N-(1-(tert-butoxycarbonyl)-3-methylazetidine-3-carbonyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl )ethyl)cyclobutyl)homoserine; N-(1-(tert-butoxycarbonyl)azetidine-3-carbonyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl) cyclobutyl)homoserine; N-(1-(methylsulfonyl)piperidine-3-carbonyl)- O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl) - homoserine; O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)-N-(4,5,6,7-tetrahydro -1H-indazole-6-carbonyl)- homoserine; O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)-N-(4,5,6,7-tetrahydro -1H-indazole-7-carbonyl)homoserine; N-(4-methyltetrahydro-2H-pyran-4-carbonyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl )cyclobutyl) homoserine; N-(1-methyl-4,5,6,7-tetrahydro-1H-indazole-6-carbonyl)-O-(3-(2-(5,6,7,8-tetrahydro-1 ,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine; N-(1-ethyl-4,4-difluorocyclohexane-1-carbonyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl )ethyl)cyclobutyl)homoserine; N-(1-(6-methylindoline-1-carbonyl)cyclopropane-1-carbonyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2- yl)ethyl)cyclobutyl)homoserine; N-(4-(((tert-butoxycarbonyl)amino)methyl)tetrahydro-2H-pyran-4-carbonyl)-O-(3-(2-(5,6,7,8-tetrahydro- 1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine; N-(1-(pyridin-3-ylmethyl)cyclopropane-1-carbonyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl) ethyl)cyclobutyl)homoserine; N-(3-chloro-5-methylisonicotinoyl)-O-(4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl)homoserine; N-(4-methyltetrahydro-2H-pyran-4-carbonyl)-O-(4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl)homoserine; N-(2,6-dichlorobenzoyl)-O-(4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl)homoserine; N-(3,5-dichloroisonicotinoyl)-O-(4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl)homoserine; N-(1-(4-(tert-butyl)phenyl)cyclobutane-1-carbonyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2 -yl)ethyl)cyclobutyl)homoserine; N-(4-methyltetrahydro-2H-pyran-4-carbonyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl )cyclobutyl)homoserine; O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)-N-(4-(trifluoromethyl)tetrahydro-2H- pyran-4-carbonyl)homoserine; N-(3-chloro-5-methylisonicotinoyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine; N-(3,5-dichloroisonicotinoyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine; N-(bicyclo[2.2.2]octane-2-carbonyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl )homoserine; N-(2-methyl-1,2,3,4-tetrahydronaphthalene-2-carbonyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin -2-yl)ethyl)cyclobutyl)homoserine; N-((methylsulfonyl)prolyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine; N-(2,4-dimethylnicotinoyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine; N-(4-phenyltetrahydro-2H-pyran-4-carbonyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl )cyclobutyl)homoserine; N-(4-cyano-2,6-dimethylbenzoyl)-O-(3-(2- (5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine ; O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)-N-(2,4,6-trimethylpyrimidine-5-carbonyl )homoserine; O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)-N-(2,4,6-trimethylnicotinoyl)homoserine; N-(3-chloro-5-fluoroisonicotinoyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine; N-(1-(isoquinolin-1-yl)cyclopropane-1-carbonyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl) ethyl)cyclobutyl)homoserine; N-(2-(pyridin-2-yl)spiro[3.3]heptane-2-carbonyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin- 2-yl)ethyl)cyclobutyl)homoserine; N-(2-(1-methyl-1H-pyrazol-4-yl)tetrahydrofuran-2-carbonyl)-O-(3-(2-(5,6,7,8-tetrahydro-1, 8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine; N-(2,4-dimethyl-6-oxo-1,6-dihydropyridine-3-carbonyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8 -naphthyridin-2-yl)ethyl)cyclobutyl)homoserine; N-(4,6-dimethylpyrimidine-5-carbonyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine ; N-(2,6-dichloro-4-(trifluoromethyl)benzoyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl) cyclobutyl)homoserine; N-(1-(2-fluorophenyl)cyclopropane-1-carbonyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl) cyclobutyl)homoserine; N-(1-(benzo[d][1,3]dioxol-5-yl)cyclohexane-1-carbonyl)-O-(3-(2-(5,6,7,8-tetrahydro -1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine; N-(2,2-difluoro-1-(m-tolyl)cyclopropane-1-carbonyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin- 2-yl)ethyl)cyclobutyl)homoserine; O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)-N-(1-(tetrahydro-2H-pyran- 2-yl)cyclopropane-1-carbonyl)homoserine; N-(4-methoxy-2,6-dimethylbenzoyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine ; N-(1-acetyl-4-(trifluoromethyl)piperidine-4-carbonyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl) ethyl)cyclobutyl)homoserine; N-(2,3-dihydrobenzo[b][1,4]dioxin-2-carbonyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8- naphthyridin-2-yl)ethyl)cyclobutyl)homoserine; N-(1-(3-chlorobenzyl)cyclopentane-1-carbonyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl) cyclobutyl)homoserine; O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)-N-(1-(3-(trifluoromethoxy)phenyl)cyclopropane -1-carbonyl)homoserine; N-(4-fluoro-2,6-dimethylbenzoyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine ; N-(3,5-dimethylisonicotinoyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine; N-(2-(tert-butyl)pyrimidin-4-yl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl) cyclobutyl)homoserine; N-(4-(tert-butyl)pyrimidin-2-yl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl) cyclobutyl)homoserine; O-(3-(2-(1,8-naphthyridin-2-yl)ethyl)cyclobutyl)-N-(quinazolin-4-yl)homoserine; N-(6-(tert-butyl)pyrimidin-4-yl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl) cyclobutyl)homoserine; 2-[(4-amino-2,6-dichlorobenzoyl)amino]-4-[3-[2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl acid) )ethyl]cyclobutoxy]butanoic acid; N-(4-chloro-2,6-dimethylnicotinoyl)-O-(3-(2- (5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)- homoserine; 2-[(3-chloro-6-methyl-pyridine-2-carbonyl)amino]-4-[3-[2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2) acid -yl)ethyl]cyclobutoxy]butanoic acid; N-(2,6-dimethylpiperidine-1-carbonyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)- homoserine; N-(2,5-dimethylpyrrolidine-1-carbonyl)-O-(3- (2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)- homoserine; N-(2,6-dichloro-4-cyanobenzoyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)- homoserine; N-(2,6-dichloro-3-nitrobenzoyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)- homoserine; 4-[3-[2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl]cyclobutoxy]-2-[(1,2,4-trimethyl-6) acid -oxo-pyridine-3-carbonyl)amino]butanoic acid; N-(2-chloro-4-cyano-6-methylbenzoyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl )-homoserine; N-(3-bromo-5-chloro-2-fluoroisonicotinoyl)- O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl )- homoserine; O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)-N-(5,6,7,8-tetrahydronaphthalene -1-carbonyl)- homoserine; N-(3-bromo-2,6-dimethylbenzoyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)- homoserine; 2-[(3-chloro-5-methoxy-pyridine-4-carbonyl)amino]-4-[3-[2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2) acid -yl)ethyl]cyclobutoxy]butanoic acid; 2-[(2,6-dichloro-4-fluoro-benzoyl)amino]-4-[3-[2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl acid) )ethyl]cyclobutoxy]butanoic acid; 2-[(2-chloro-6-fluoro-benzoyl)amino]-4-[3-[2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl acid ]cyclobutoxy]butanoic acid; N-(3-bromo-2-chloro-6-fluorobenzoyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl )-homoserine; N-(2,4-dimethyl-6-oxo-1-phenyl-1,6-dihydropyridine-3-carbonyl)-O-(3-(2-(5,6,7,8-tetrahydro -1,8- naphthyridin-2-yl)ethyl)cyclobutyl)-homoserine; N-(5-bromo-2-hydroxy-isonicotinoyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)- homoserine; N-(3-chloro-5-cyclopropylisonicotinoyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)-homoserine; N-(3-chloro-5-ethylisonicotinoyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)-homoserine; N-(3-cyano-2,6-dimethylbenzoyl)-O-(3-(2- (5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)- homoserine; N-(3-bromo-5-fluoroisonicotinoyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)-homoserine; N-(2-methoxy-3,5-dimethylisonicotinoyl)-O-(3- (2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)- homoserine; N-(3-chloro-5-(trifluoromethyl)isonicotinoyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl) -homoserine; N-(3-bromo-5-chloroisonicotinoyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)-homoserine; N-(2-(dimethylamino)-3,5-dimethylisonicotinoyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl )-homoserine; N-(3-chloro-5-fluoro-2-methylisonicotinoyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl )-homoserine; N-(2,6-dichloro-3-cyanobenzoyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)- homoserine; N-(3-methyl-5-(trifluoromethyl)isonicotinoyl)- O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl) - homoserine; N-(2-hydroxy-3,5-dimethylisonicotinoyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)- homoserine; N-(3-cyano-2-hydroxy-6-methylisonicotinoyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl )-homoserine; N-(5-chloro-3-fluoro-2-methylisonicotinoyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl )-homoserine; 2-[(6-methoxy-2,4-dimethyl-pyridine-3-carbonyl)amino]-4-[3-[2-(5,6,7,8-tetrahydro-1,8-naphthyridin) acid -2-yl)ethyl]cyclobutoxy]butanoic acid; 2-[[2,6-dimethyl-4-[(4-methylpiperazin-1-yl)methyl]benzoyl]amino]-4-[3-[2-(5,6,7,8-tetrahydro acid) -1,8-naphthyridin-2-yl)ethyl]cyclobutoxy]butanoic acid; N-(3,5-dimethylmorpholine-4-carbonyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)- homoserine; 2-[[5-chloro-3-fluoro-2-[(4-methylpiperazin-1-yl)methyl]pyridine-4-carbonyl]amino]-4-[3-[2-(5,6,7) acid ,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl]cyclobutoxy]butanoic acid; 2-[(7-chloro-5-oxo-2,3-dihydro-1H-indolizine-8-carbonyl)amino]-4-[3-[2-(5,6,7,8-tetra- methyl hydro-1,8-naphthyridin-2-yl)ethyl]cyclobutoxy]butanoate; 2-[(2,6-difluoro-4-hydroxy-benzoyl)amino]-4-[3-[2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl acid) )ethyl]cyclobutoxy]butanoic acid; 2-[(4-chloro-2-methyl-pyrazol-3-carbonyl)amino]-4-[3-[2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2) acid - yl)ethyl]cyclobutoxy]butanoic acid; 2-[(2-methylpyrazol-3-carbonyl)amino]-4-[3-[2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl]cyclobutoxy acid ]butanoic; N-(1-(phenylsulfonyl)piperidine-2-carbonyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl) -homoserine; 2-(3,3-dimethylbutanoylamino)-4-[3-[2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl]cyclobutoxy]butanoic acid; 2-[(2-phenylacetyl)amino]-4-[3-[2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl]cyclobutoxy]butanoic acid; 4-[3-[2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl]cyclobutoxy]-2-[(4,4,4-trifluoro-3) acid ,3-dimethyl-butanoyl)amino]butanoic acid; 2-[(4,4-difluoro-3,3-dimethyl-butanoyl)amino]-4-[3-[2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2) acid - yl)ethyl]cyclobutoxy]butanoic acid; 2-[[2-phenylpropanoyl]amino]-4-[3-[2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl]cyclobutoxy]butanoic acid; 2-[[2-(3,5-difluorophenyl)acetyl]amino]-4-[3-[2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl) acid ethyl]cyclobutoxy]butanoic acid; 2-[[2-(tert-butoxycarbonylamino)-1-methyl-ethoxy]carbonylamino]-4-[3-[2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2) acid -yl)ethyl]cyclobutoxy]butanoic acid; 2-[(3,6-dimethylpyridine-2-carbonyl)amino]-4-[3-[2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl acid ]cyclobutoxy]butanoic acid; 2-[(6-fluorochromano-2-carbonyl)amino]-4-[3-[2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl]cyclobutoxy acid ]butanoic; 4-[3-[2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl]cyclobutoxy]-2-[2-[3-(trifluoromethyl)phenyl] acid butanoylamino]butanoic acid; 2-[(3-chloro-5-methyl-pyridine-4-carbonyl)amino]-4-[3-[2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2) acid - yl)ethyl]cyclobutoxy]butanoic acid; 2-[(3-chloro-5-fluoro-pyridine-4-carbonyl)amino]-4-[3-[2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2) acid - yl)ethyl]cyclobutoxy]butanoic acid; 2-[(4-cyano-2,6-dimethyl-benzoyl)amino]-4-[3-[2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl acid) )ethyl]cyclobutoxy]butanoic acid; 2-[[4-(2-chlorophenyl)tetrahydropyran-4-carbonyl]amino]-4-[3-[2-(5,6,7,8-tetrahydro-1,8-naphthyridin-) acid 2-yl)ethyl]cyclobutoxy]butanoic acid; 2-[(2-hydroxy-indane-2-carbonyl)amino]-4-[3-[2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl acid ]cyclobutoxy]butanoic acid; 2-[(1-cyclopropylcyclopropanecarbonyl)amino]-4-[3-[2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl]cyclobutoxy]butanoic acid; 2-[[3-(difluoromethyl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyridine-6-carbonyl]amino]-4-[ acid 3-[2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl]cyclobutoxy]butanoic acid; 2-[(1-cyclopropylcyclobutanecarbonyl)amino]-4-[3-[2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl]cyclobutoxy]butanoic acid; 2-[[1-(4-isopropylphenyl)cyclopentanecarbonyl]amino]-4-[3-[2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl] acid cyclobutoxy]butanoic acid; 2-(bicyclo[2.2.2]octane-4-carbonylamino)-4-[3-[2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl] acid cyclobutoxy]butanoic acid; 2-(3,4,5,6,7,7a-hexahydro-2H-benzofuran-3a-carbonylamino)-4-[3-[2-(5,6,7,8-tetrahydro-) acid 1,8-naphthyridin-2-yl)ethyl]cyclobutoxy]butanoic acid; 2-[[1-(2-phenylethyl)cyclopropanecarbonyl]amino]-4-[3-[2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl] acid cyclobutoxy]butanoic acid; 2-[[4-(3-methylisoxazol-5-yl)tetrahydropyran-4-carbonyl]amino]-4-[3-[2-(5,6,7,8-tetrahydro-1) acid, 8-naphthyridin-2-yl)ethyl]cyclobutoxy]butanoic acid; 2-[[1-(benzenesulfonyl)cyclopropanecarbonyl]amino]-4-[3-[2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl]cyclobutoxy acid] butanoic; 2-[(1-phenylcycloheptanecarbonyl)amino]-4-[3-[2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl]cyclobutoxy]butanoic acid ; 2-[(4-methylsulfonyltetrahydropyran-4-carbonyl)amino]-4-[3-[2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl acid ]cyclobutoxy]butanoic acid; 2-[[1-(4-sulfamoylphenyl)cyclopropanecarbonyl]amino]-4-[3-[2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl] acid cyclobutoxy]butanoic acid; N-((phenylsulfonyl)prolyl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)-homoserine; N-(5-chloro-3-fluoro-2-((4-methylpiperazin-1-yl)methyl)isonicotinoyl)-O-(3-(2-(5,6,7,8-tetrahydro-1 ,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine; N-(3-chloro-5-fluoro-2-((4-methylpiperazin-1-yl)methyl)isonicotinoyl)-O-(3-(2- (5,6,7,8-tetrahydro-1 ,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine; 2-(pyrimidin-4-ylamino)-5-(3-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)propoxy)pentanoic acid; 2-[(3-chloro-5-methyl-pyridine-4-carbonyl)amino]-4-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl) acid butoxy]butanoic; 2-[(2,4-dimethylpyridin-3-carbonyl)amino]-4-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butoxy]butanoic acid; 2-[(4-cyano-2,6-dimethyl-benzoyl)amino]-4-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butoxy acid] butanoic; 2-[(3,5-dichloropyridin-4-carbonyl)amino]-4-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butoxy]butanoic acid; 2-[(3-chloro-5-fluoro-pyridine-4-carbonyl)amino]-4-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl) acid butoxy]butanoic acid; N-(3,5-dimethylmorpholine-4-carbonyl)-O-(4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl)-homoserine; N-(2,6-dichlorobenzoyl)-O-(4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl)-homoserine; N-(3,5-dimethylisonicotinoyl)-O-(4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl)-homoserine; 2-[(2,4-dichloro-6-fluoro-benzoyl)amino]-4-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butoxy acid] butanoic; 2-[(2,4-dimethyl-6-oxo-1H-pyridine-3-carbonyl)amino]-4-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin- acid) 2-yl)butoxy]butanoic acid; N-(3-chloro-5-methoxy-isonicotinoyl)-O-(4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl)-homoserine; 2-[(2-chloro-6-fluoro-benzoyl)amino]-4-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butoxy]butanoic acid; N-(tert-butoxycarbonyl)-O-(4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl)-homoserine; N-(5-bromo-2-hydroxy-isonicotinoyl)-O-(4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl)-homoserine; N-(3-bromo-5-chloro-2-fluoroisonicotinoyl)-O-(4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl)-homoserine; N-(2,4-dimethyl-6-oxo-1-phenyl-1,6-dihydropyridine-3-carbonyl)-O-(4-(5,6,7,8-tetrahydro-1, 8-naphthyridin-2-yl)butyl)-homoserine; O-(4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl)-N-(5,6,7,8-tetrahydronaphthalene-1-carbonyl) -homoserine; N-(3-bromo-2,6-dimethylbenzoyl)-O-(4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl)-homoserine; N-(3-chloro-5-fluoroisonicotinoyl)-O-(4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl)-homoserine; N-(3-bromo-2-chloro-6-fluorobenzoyl)-O-(4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl)-homoserine; 2-[(3-chloro-5-methoxy-pyridine-4-carbonyl)amino]-4-[2-methyl-4-(5,6,7,8-tetrahydro-1,8-naphthyridin-) acid 2-yl)butoxy]butanoic acid; 2-[(3-chloro-5-fluoro-pyridine-4-carbonyl)amino]-4-[2-methyl-4-(5,6,7,8-tetrahydro-1,8-naphthyridin- acid) 2-yl)butoxy]butanoic acid; N-(3-chloro-5-fluoroisonicotinoyl)-O-(2-methyl-4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl)-homoserine; N-(2,6-dichlorobenzoyl)-O-(2-methyl-4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl)-homoserine; N-(2-chloro-6-fluorobenzoyl)-O-(2-methyl-4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl)-homoserine; N-(2-chloro-6-fluorobenzoyl)-O-(4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl)-L-homoserine; N-(4-fluoro-2-methylnicotinoyl)-O-(2-methyl-4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl)-homoserine; 2-[(3-chloro-5-fluoro-pyridine-4-carbonyl)amino]-4-[2-hydroxy-4-(5,6,7,8-tetrahydro-1,8-naphthyridin-) acid 2-yl)butoxy]butanoic acid; 2-(1-methyl-1H-indazol-4-carboxamido)-5-(3-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)propoxy)pentanoic acid; 2-(3-(1-methyl-1H-pyrazol-4-yl)benzamido)-5-(3-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl) acid propoxy)pentanoic; 2-(2-chloro-3-fluorobenzamido)-6-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethoxy)hexanoic acid; 2-(3-(1-methyl-1H-pyrazol-4-yl)benzamido)-6-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl) acid ethoxy)hexanoic; 2-(2-ethylbutanamido)-6-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethoxy)hexanoic acid; 2-(1-methyl-1H-indazol-4-carboxamido)-6-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethoxy)hexanoic acid; 2-((tert-butoxycarbonyl)amino)-5-(3-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)propoxy)pentanoic acid; N-benzoyl-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine; N-(quinazolin-4-yl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine; N-(8-fluoroquinazolin-4-yl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine; N-(7-fluoroquinazolin-4-yl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine; N-(7-methylquinazolin-4-yl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine; N-(6-fluoroquinazolin-4-yl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine; N-(5-fluoroquinazolin-4-yl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine; N-(6-methylquinazolin-4-yl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)cyclobutyl)homoserine; and N-(6-(tert-butyl)-2-phenylpyrimidin-4-yl)-O-(3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2- yl)ethyl)cyclobutyl)-homoserine; or a salt thereof. 4. Pharmaceutical composition, characterized by the fact that it comprises a compound, as defined in any one of claims 1 to 3, or a salt thereof, and a pharmaceutically acceptable carrier or excipient. 5. Use of a compound as defined in any one of claims 1 to 3, or a pharmaceutically acceptable salt thereof, characterized in that it is for the manufacture of a medicament, composition, product, or kit for treating a fibrotic disease in an individual in need thereof, preferably in which the fibrotic disease is pulmonary fibrosis, hepatic fibrosis, skin fibrosis, cardiac fibrosis, renal fibrosis, gastrointestinal fibrosis, primary sclerosing cholangitis or biliary fibrosis. 6. Kit, characterized in that it comprises a compound, as defined in any one of claims 1 to 3, or a pharmaceutically acceptable salt thereof, optionally further comprising instructions for treating a fibrotic disease. 7. Use of a compound as defined in any one of claims 1 to 3, or a pharmaceutically acceptable salt thereof, characterized in that it is for the manufacture of a medicament, composition, product, or kit for inhibiting the αVβ6 integrin in an individual. 8. Use of a compound as defined in any one of claims 1 to 3, or a pharmaceutically acceptable salt thereof, characterized in that it is for the manufacture of a medicament, composition, product, or kit for inhibiting the activation of TGFβ in a cell. 9. Use of a compound as defined in any one of claims 1 to 3, or a pharmaceutically acceptable salt thereof, characterized in that it is for the manufacture of a medicament, composition, product, or kit for modulating at least one integrin in an individual, wherein the at least one integrin comprises an αV subunit, wherein the medicament, composition, product, or kit comprises an effective amount of: the compound as defined in any one of claims 1 to 3, or an pharmaceutically acceptable salt thereof. 10. Use of a compound as defined in any one of claims 1 to 3, or a pharmaceutically acceptable salt thereof, characterized in that it is for manufacturing a medicament, composition, product, or kit for treating an individual in need. of the same, wherein the individual has at least one tissue in need of therapy and the tissue has at least a high level of: TGFβ activation and/or expression; αVβ1 integrin activity and/or expression; or αVβ6 integrin activity and/or expression; wherein the at least one elevated level is elevated compared to a healthy state of the tissue. 11. Method, characterized by the fact that it is for producing a compound, as defined in claim 1, or a salt thereof. 12. Compound, characterized by the fact that it is selected from: or a salt thereof. 13. Invention in any form of its embodiments or categories of applicable claims, for example, product or process or use encompassed by the matter initially described, disclosed or illustrated in the patent application; Use of a compound as defined in any one of claims 1 to 3, or a pharmaceutically acceptable salt thereof, in the manufacture of a pharmaceutical composition, medicament, composition, product, or kit for preventing or treating a disease or condition in an individual , to inhibit the integrin αVβ6 in an individual, to inhibit the activation of TGFβ in a cell, to modulate at least one integrin in an individual, and/or to modulate the activation of TGFβ in a cell; Use of a compound as defined in any one of claims 1 to 3, or a pharmaceutically acceptable salt thereof, in the manufacture of a pharmaceutical composition, medicament, composition, product, or kit for preventing or treating a disease or condition in an individual , to treat or prevent a disease, disorder or health condition; Use of a compound as defined in any one of claims 1 to 3, or a pharmaceutically acceptable salt thereof, in the manufacture of a pharmaceutical composition, medicament, composition, product, or kit for preventing or treating a disease or condition in an individual , to treat or prevent a fibrotic disease; Kit comprising a compound as defined in any one of claims 1 to 3, or a pharmaceutically acceptable salt thereof; Method for modulating the activation of TGFβ in a cell, comprising contacting the cell with: the compound as defined in any one of claims 1 to 3, or a pharmaceutically acceptable salt thereof, or the pharmaceutical composition as defined in claim 4.