WO2024236538A1

WO2024236538A1 - Azetidine linked bicyclic heterocyclyl compounds as ccr4 modulators

Info

Publication number: WO2024236538A1
Application number: PCT/IB2024/054799
Authority: WO
Inventors: Chandrasekhar ABBINENI; Susanta Samajdar; Krishna Chaitanya TALLURI; Subhendu MUKHERJEE; Chandrasekhar V MIDUTURU
Original assignee: Aurigene Oncology Limited
Priority date: 2023-05-17
Filing date: 2024-05-17
Publication date: 2024-11-21

Abstract

The present disclosure provides azetidine linked bicyclic heterocyclyl compounds of formula (I-1), which are therapeutically useful as CCR4 modulators. These compounds are useful in the treatment and/or prevention of diseases and/or disorders responsive to the modulation of CCR4 activity. Compounds of the present disclosure are especially useful for treating cancer and inflammatory diseases and disorders. The present disclosure also provides processes for preparation of the compounds and pharmaceutical formulations comprising at least one of the compounds of formula (I-1) or a pharmaceutically acceptable salt or a stereoisomer thereof.

Description

AZETIDINE LINKED BICYCLIC HETEROCYCLYL COMPOUNDS AS CCR4 MODULATORS CROSS REFERENCE TO RELATED APPLICATIONS The present application claims priority to and the benefit of Indian Patent Application No. IN 202341034417, filed on May 17, 2023, which application is incorporated herein by reference in their entirety. TECHNICAL FIELD The present application is directed to azetidine linked bicyclic heterocyclyl compounds of formula (I-1) as CCR4 modulators, useful for the treatment of cancer and inflammatory diseases or disorders. The disclosure also provides pharmaceutically acceptable compositions comprising compounds of the present application and methods of using said compositions in the treatment of diseases associated with CCR4. BACKGROUND Innate and adaptive immune responses and their coordinated interplay are essential to maintain homeostasis and for effective immune surveillance against pathogens and inflammatory diseases. The key mediators of the immune system include the immune cells and the cytokines produced by them. Chemokines are a family of small, secreted cytokines that control several processes such as cellular adhesion, localization, migration and cell-cell interaction (Clemens Esche, J Invest Dermatol.2005 Oct;125(4):615-28). Inflammatory chemokines secreted by various types of cells control the recruitment of inflammatory effector cells such as leukocytes in response to infection, inflammation, tissue injury and in the tumor microenvironment (Anna E Vilgelm, Front Immunol. 2019 Feb 27;10:333). They exert their effect through the activation of chemokine receptors on the cell surface of the effector cells. Chemokine receptors belong to the large family of G-protein coupled receptors (GPCR). Cells expressing the chemokine receptors migrate in the direction of the respective chemokine gradient secreted by the tissue resident cells. CCR4 (C-C chemokine receptor) is an important member of the GPCR family that plays a critical role in the migration of immune cells in response to inflammatory chemokines CCL22 and CCL17 (Hongyi Li, MedComm (2020).2022 Jun 8;3(2):e147). Tumor cells and tumor-associated macrophages secrete CCL22 leading to the recruitment of CCR4 expressing regulatory T cells (Tregs) in the tumor microenvironment. This increased infiltration of Tregs leads to an immune-suppressive tumor microenvironment and is associated with poor prognosis (Osamu Yoshie, Cancers (Basel). 2021 Nov 4;13(21):5542). Thus, CCR4 is implicated in the pathology of various immune-associated disorders. Effective modulation of CCR4 is hence crucial for the therapeutic intervention of inflammatory disorders and cancer. SUMMARY Provided herein are compounds of formula (I-1) and pharmaceutical compositions thereof, which are capable of modulating CCR4. In one aspect of the present disclosure, it comprises compounds of formula (I-1):

or a pharmaceutically acceptable salt or a stereoisomer thereof; wherein, W1 is C, N or O; X₁ and X₂ are each independently CH, N, NR_x, O or S; X₃, X₄ and X₅ are each independently CH or N; Rx is hydrogen or alkyl; R1 at each occurrence is independently alkyl, alkenyl, alkynyl, halo, cyano, amino, nitro, -OR_1a, -C(O)R_1b or cycloalkyl; wherein each of alkyl, alkenyl, alkynyl and cycloalkyl is optionally substituted with one or more substituents independently selected from halo, hydroxy and alkoxy; R₂ and R₂' are each independently hydrogen or alkyl; R₃ is hydrogen or alkyl; R4 at each occurrence is independently alkyl, alkenyl, alkynyl, halo, cyano, amino, nitro, -OR4a, -C(O)R4b or cycloalkyl; wherein each of alkyl, alkenyl, alkynyl and cycloalkyl is optionally substituted with one or more substituents independently selected from hydroxy, halo and alkoxy; each R1a and R4a is independently hydrogen, alkyl, haloalkyl, cycloalkyl or heterocycloalkyl; R₅ at each occurrence is independently halo, alkyl, haloalkyl, alkoxy or -C(O)R_5a; each R1b, R4b and R5a is independently hydrogen, alkyl, amino, alkylamino, hydroxy, haloalkyl, cycloalkyl or heterocycloalkyl; R₆ is alkyl, heterocycloalkyl or -C(O)R_6c; wherein each alkyl and heterocycloalkyl is optionally substituted with one or more substituents independently selected from hydroxy, - NR6aR6b, halo and cycloalkyl, wherein the cycloalkyl is optionally substituted with one or more substituents independently selected from hydroxy, halo, alkyl, acyl and alkoxy; each R6a and R6b is independently hydrogen, alkyl, acyl or alkylsulfonyl; R6c is independently alkyl, heterocycloalkyl or cycloalkyl, wherein each alkyl, heterocycloalkyl and cycloalkyl is optionally substituted with one or more substituents independently selected from hydroxy, halo, alkyl, acyl and alkoxy; ‘m’ is an integer from 0 to 5; ‘n’ is an integer from 0 to 3; ‘j’ is an integer from 0 to 4; and ‘k’ is an integer from 0 to 2. In yet another aspect, the present application provides pharmaceutical compositions comprising a compound of formula (I-1) or a pharmaceutically acceptable salt thereof and at least one pharmaceutically acceptable excipient (such as a pharmaceutically acceptable carrier or diluent). In yet another aspect, the present application relates to the preparation of compounds of formula (I-1). In yet another aspect of the present application, provided herein are compounds of formula (I-1), which are capable of modulating CCR4 and therapeutic use thereof. DETAILED DESCRIPTION Unless defined otherwise, all technical and scientific terms used herein have the same meaning as is commonly understood by one of skill in art to which the subject matter herein belongs. As used in the specification and the appended claims, unless specified to the contrary, the following terms have the meaning indicated to facilitate the understanding of the present disclosure. As used herein, unless otherwise defined the term "alkyl" alone or in combination with other term(s) means saturated aliphatic hydrocarbon chains, including C1-C10 straight or C1-C10 branched alkyl groups. Examples of "alkyl" include but are not limited to methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, isopentyl or neopentyl and the like. As used herein, unless otherwise defined the term "alkenyl" alone or in combination with other term(s) means unsaturated aliphatic hydrocarbon chains, including C1-C10 straight or C₁-C₁₀ branched alkyl groups. An alkenyl may include more than one double bond and/or one or more triple bonds in addition to the one or more double bonds. Examples of "alkenyl" include but are not limited to vinyl, 2-propenyl, 2-isopentenyl, 2-(butadienyl), 2,4-pentadienyl, 3-(1,4-pentadienyl) and the like. As used herein, unless otherwise defined the term "alkynyl" alone or in combination with other term(s) means unsaturated aliphatic hydrocarbon chains, including C1-C10 straight or C1-C10 branched alkyl groups. An alkynyl may include more than one triple bond and/or one or more double bonds in addition to the one or more triple bonds. Examples of "alkynyl" include but are not limited to ethynyl, 1- and 3-propynyl, 3-butynyl and the like. As used herein, the term "halo" or "halogen" alone or in combination with other term(s) means fluorine, chlorine, bromine or iodine. As used herein, the term "haloalkyl" means alkyl substituted with one or more halogen atoms, wherein the alkyl groups are as defined above. The term "halo" is used herein interchangeably with the term "halogen" means F, Cl, Br or I. Examples of "haloalkyl" include but are not limited to fluoromethyl, difluoromethyl, chloromethyl, trifluoromethyl, 2,2,2- trifluoroethyl and the like. As used herein, the term "hydroxy" or "hydroxyl" alone or in combination with other term(s) means –OH. As used herein, the term "hydroxyalkyl" refers to the group HO-alkyl-, wherein alkyl and hydroxy groups are as defined herein. As used herein, the term “acyl” refers to a group R-C(O)- wherein R is an optionally substituted alkyl group defined above. Examples of ‘acyl’ groups are, but not limited to, CH₃CO-, CH₃CH₂CO-, CH₃CH₂CH₂CO- or (CH₃)₂CHCO-. As used herein, the term “alkylsulfonyl” refers to a group R-SO2- wherein R is an optionally substituted alkyl group defined above. Examples of ‘alkylsulfonyl’ groups are, but not limited to, CH₃SO₂-, CH₃CH₂SO₂-, CH₃CH₂CH₂SO₂-, or (CH₃)₂CHSO₂-. As used herein, the term "alkoxy" alone or in combination with other term(s) refers to the group alkyl-O- or –O-alkyl, where alkyl groups are as defined above. Exemplary C1-C10 alkyl group containing alkoxy- groups include but are not limited to methoxy, ethoxy, n- propoxy, n-butoxy, t-butoxy and the like. An alkoxy group can be unsubstituted or substituted with one or more suitable groups. The term "amino" or "amine" alone or in combination with other term(s) refers to a primary amine (–NH₂), secondary amine

, wherein ‘N’ is substituted with two substituents other than hydrogen) or tertiary amine ( , wherein ‘N’ is substituted with three substituents other than hydrogen) group. As used herein, the term "alkylamino" alone or in combination with other term(s) means an amino group as defined above, substituted with one or more "alkyl" group, wherein the alkyl group and amino group is as defined above. Examples of "alkylamino" groups include but are not limited to -NHCH₃, -NHCH₂CH₃, -N(CH₃)₂, -N(CH₃)(CH₂CH₃) and the like. As used herein, the term "cyano" refers to –CN; and the term "cyanoalkyl" refers to alkyl substituted with -CN; wherein the alkyl groups are as defined above. As used herein, the term "nitro" refers to –NO₂; As used herein the term "cycloalkyl" alone or in combination with other term(s) means C3-C10 saturated cyclic hydrocarbon ring. A cycloalkyl may be a single ring, which typically contains from 3 to 7 carbon ring atoms. Examples of single-ring cycloalkyls include but are not limited to cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl and the like. A cycloalkyl may alternatively be polycyclic or contain more than one ring. Examples of polycyclic cycloalkyls include bridged, fused and spirocyclic carbocyclyls and the like. As used herein, the term "aryl" is unsubstituted or substituted monocyclic, bicyclic or polycyclic aromatic hydrocarbon ring system of about 6 to 14 carbon atoms. Examples of a C6- C14 aryl group include, but are not limited to phenyl, naphthyl, anthryl, tetrahydronaphthyl, fluorenyl, indanyl, biphenylenyl and acenaphthyl. An aryl group may be unsubstituted or substituted with one or more suitable groups. As used herein, the term "carbocyclyl" alone or in combination with other term(s) includes both "cycloalkyl" and "aryl" groups which are as defined above. Examples of "carbocyclyl" include, but are not limited to cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl and naphthyl. The term "heterocycloalkyl" refers to a non-aromatic, saturated or partially saturated monocyclic or polycyclic ring system of 3 to 15 members having at least one heteroatom or heterogroup selected from O, N, S, S(O), S(O)₂, NH or C(O) with the remaining ring atoms being independently selected from the group consisting of carbon, oxygen, nitrogen and sulfur. A monocyclic heterocycloalkyl may typically contain 4 to 7 ring atoms. Examples of “heterocycloalkyl” include, but are not limited to azetidinyl, oxetanyl, imidazolidinyl, pyrrolidinyl, oxazolidinyl, thiazolidinyl, pyrazolidinyl, tetrahydrofuranyl, piperidinyl, piperazinyl, tetrahydropyranyl, morpholinyl, oxapiperazinyl, oxapiperidinyl, tetrahydrofuryl, tetrahydropyranyl, tetrahydrothiophenyl, dihydropyranyl, indolinyl, azepanyl and N-oxides thereof. Attachment of a heterocycloalkyl substituent can occur via either a carbon atom or a heteroatom. A heterocycloalkyl group can be unsubstituted or substituted with one or more suitable groups by one or more aforesaid groups. As used herein, the term "heteroaryl" alone or in combination with other term(s) means a completely unsaturated ring system containing a total of 5 to 14 ring atoms. At least one of the ring atoms is a heteroatom (i.e., oxygen, nitrogen, or sulfur), with the remaining ring atoms/groups being independently selected from the group consisting of carbon, oxygen, nitrogen or sulfur. A heteroaryl may be a single-ring (monocyclic) or polycyclic ring system. Examples of "heteroaryl" include but are not limited to pyridyl, indolyl, benzimidazolyl, benzothiazolyl and the like. As used herein, the term "heterocyclyl" alone or in combination with other term(s) includes both "heterocycloalkyl" and "heteroaryl" groups which are as defined above. Examples of “Heterocyclyl” include, but are not limited to azetidinyl, pyrrolidinyl, piperidinyl, pyridyl, indolyl, benzimidazolyl, benzothiazolyl and the like. The term "heteroatom" as used herein designates a sulfur, nitrogen or oxygen atom. As used in the above definitions, the term "optionally substituted" or “substituted” or “optionally substituted with suitable groups” refers to replacement of one or more hydrogen radicals in a given structure with a radical of a specified substituent including, but not limited to: halo, alkyl, alkenyl, alkynyl, aryl, heterocyclyl, thiol, alkylthio, arylthio, alkylthioalkyl, arylthioalkyl, alkylsulfonyl, alkylsulfonylalkyl, arylsulfonylalkyl, alkoxy, aryloxy, aralkoxy, aminocarbonyl, alkylaminocarbonyl, arylaminocarbonyl, alkoxycarbonyl, aryloxycarbonyl, haloalkyl, amino, trifluoromethyl, cyano, nitro, alkylamino, arylamino, alkylaminoalkyl, arylaminoalkyl, aminoalkylamino, hydroxy, alkoxyalkyl, carboxyalkyl, alkoxycarbonylalkyl, aminocarbonylalkyl, acyl, aralkoxycarbonyl, carboxylic acid, sulfonic acid, sulfonyl, phosphonic acid, aryl, heteroaryl, heterocyclic and aliphatic. It is understood that any substituent may be further substituted. As used herein, the term 'compound(s)' comprises the compounds disclosed in the present disclosure. As used herein, the term "comprise" or "comprising" is generally used in the sense of include, that is to say permitting the presence of one or more features or components. As used herein, the term "or" means "and/or" unless stated otherwise. As used herein, the term "including" as well as other forms, such as "include", "includes" and "included" is not limiting. As used herein, the term "composition" is intended to encompass a product comprising the specified ingredients in the specified amounts, as well as any product which results, directly or indirectly, from combination of the specified ingredients in the specified amounts. By "pharmaceutically acceptable" it is meant the carrier, diluent or excipient must be compatible with the other ingredients of the formulation and not deleterious to the recipient thereof. As used herein, the term "treat", "treating" and "treatment" refer to a method of alleviating or abrogating a disease and/or its attendant symptoms. As used herein, the term "prevent", "preventing" and "prevention" refer to a method of preventing the onset of a disease and/or its attendant symptoms or barring a subject from acquiring a disease. As used herein, "prevent", "preventing" and "prevention" also include delaying the onset of a disease and/or its attendant symptoms and reducing a subject's risk of acquiring a disease. As used herein, the term "therapeutically effective amount" refers to that amount of the compound being administered sufficient to prevent development of or alleviate to some extent one or more of the symptoms of the condition or disorder being treated. "Pharmaceutically acceptable" means that, which is useful in preparing a pharmaceutical composition that is generally safe, non-toxic and neither biologically nor otherwise undesirable and includes that which is acceptable for veterinary as well as human pharmaceutical use. As used herein, the phrase "pharmaceutically acceptable excipient" refers to a pharmaceutically acceptable material, composition, or vehicle, such as a liquid or solid filler, diluent, solvent, or encapsulating material. Excipients or carriers are generally safe, non-toxic and neither biologically nor otherwise undesirable and include excipients or carriers that are acceptable for veterinary use as well as human pharmaceutical use. In one embodiment, each component is "pharmaceutically acceptable" as defined herein. See, e.g., Remington: The Science and Practice of Pharmacy, 21st ed.; Lippincott Williams & Wilkins: Philadelphia, Pa., 2005; Handbook of Pharmaceutical Excipients, 6th ed.; Rowe et al, Eds.; The Pharmaceutical Press and the American Pharmaceutical Association: 2009; Handbook of Pharmaceutical Additives, 3rd ed.; Ash and Ash Eds. ; Gower Publishing Company: 2007; Pharmaceutical Preformulation and Formulation, 2nd ed. ; Gibson Ed.; CRC Press LLC: Boca Raton, Fla., 2009. As used herein, “pharmaceutically acceptable salt(s)” refers to derivatives of the disclosed compounds wherein the parent compound is modified by converting an existing acid or base moiety to its salt form. Examples of pharmaceutically acceptable salts include, but are not limited to, mineral or organic acid salts of basic residues such as amines; alkali or organic salts of acidic residues such as carboxylic acids; and the like. The pharmaceutically acceptable salts of the present disclosure include the conventional non-toxic salts of the parent compound formed, for example, from non-toxic inorganic or organic acids. The pharmaceutically acceptable salts of the present disclosure can be synthesized from the parent compound which contains a basic or acidic moiety by conventional chemical methods. Generally, such salts can be prepared by reacting the free acid or base forms of these compounds with a stoichiometric amount of the appropriate base or acid in water or in an organic solvent, or in a mixture of the two; generally, non-aqueous media like ether, ethyl acetate, alcohols or acetonitrile (ACN) are preferred. The term "stereoisomers" refers to any enantiomers, diastereoisomers, or geometrical isomers of the compounds of Formula (I-1), (I), (IA-1), (IB-1), (IC-1), (ID-1), (IE-1), (IF-1) & (IG-1), (IA), (IB), (IC), (ID), (IE),(IF) and (IG) wherever they are chiral or when they bear one or more double bonds. When the compounds of the formula (I-1), (I), (IA-1), (IB-1), (IC-1), (ID-1), (IE-1), (IF-1) & (IG-1), (IA), (IB), (IC), (ID), (IE), (IF) and (IG) are chiral, they can exist in racemic or in optically active form. It should be understood that the disclosure encompasses all stereochemical isomeric forms, including diastereomeric, enantiomeric and epimeric forms, as well as d-isomers and l-isomers and mixtures thereof. Individual stereoisomers of compounds can be prepared synthetically from commercially available starting materials which contain chiral centers or by preparation of mixtures of enantiomeric products followed by separation such as conversion to a mixture of diastereomers followed by separation or recrystallization, chromatographic techniques, direct separation of enantiomers on chiral chromatographic columns, or any other appropriate method known in the art. Starting compounds of particular stereochemistry are either commercially available or can be made and resolved by techniques known in the art. Additionally, the compounds of the present disclosure may exist as geometric isomers. The present disclosure includes all cis, trans, syn, anti, R and S, entgegen (E) and zusammen (Z) isomers as well as the appropriate mixtures thereof. The present disclosure provides compounds of formula (I), which are useful for the modulation of CCR4. The present disclosure further provides pharmaceutical compositions comprising the said compounds of formula (I), and their derivatives as therapeutic agents. It will be apparent to those skilled in the art that various modifications and variations can be made to the compounds, compositions, and methods described herein without departing from the scope or spirit of various embodiments disclosed herein. For instance, features illustrated or described as part of one embodiment can be applied to another embodiment to yield a still further embodiment. Thus, it is intended that the present application includes such modifications and variations and their equivalents. Other objects, features, and aspects of the present application are disclosed in, or are obvious from, the following detailed description. It is to be understood by one of ordinary skill in the art that the present discussion is a description of exemplary embodiments and is not to be construed as limiting the broader aspects of the present disclosure. The embodiments below are illustrative of the present disclosure and are not intended to limit the claims to the specific embodiments exemplified. In a first embodiment, the present application provides compounds of formula (I-1), or a pharmaceutically acceptable salt or a stereoisomer thereof; wherein, W1 is C, N or O; X₁ and X₂ are each independently CH, N, NR_x, O or S; X3, X4 and X5 are each independently CH or N; Rx is hydrogen or alkyl; R₁ at each occurrence is independently alkyl, alkenyl, alkynyl, halo, cyano, amino, nitro, -OR1a, -C(O)R1b or cycloalkyl; wherein each of alkyl, alkenyl, alkynyl and cycloalkyl is optionally substituted with one or more substituents independently selected from halo, hydroxy and alkoxy; R₂ and R₂' are each independently hydrogen or alkyl; R3 is hydrogen or alkyl; R₄ at each occurrence is independently alkyl, alkenyl, alkynyl, halo, cyano, amino, nitro, -OR_4a, -C(O)R_4b or cycloalkyl; wherein each of alkyl, alkenyl, alkynyl and cycloalkyl is optionally substituted with one or more substituents independently selected from hydroxy, halo and alkoxy; each R_1a and R_4a is independently hydrogen, alkyl, haloalkyl, cycloalkyl or heterocycloalkyl; R5 at each occurrence is independently halo, alkyl, haloalkyl, alkoxy or -C(O)R5a; each R_1b, R_4b and R_5a is independently hydrogen, alkyl, amino, alkylamino, hydroxy, haloalkyl, cycloalkyl or heterocycloalkyl; R6 is alkyl, heterocycloalkyl or -C(O)R6c; wherein each alkyl and heterocycloalkyl is optionally substituted with one or more substituents independently selected from hydroxy, - NR6aR6b, halo and cycloalkyl, wherein the cycloalkyl is optionally substituted with one or more substituents independently selected from hydroxy, halo, alkyl, acyl and alkoxy; each R_6a and R_6b is independently hydrogen, alkyl, acyl or alkylsulfonyl; R6c is independently alkyl, heterocycloalkyl or cycloalkyl, wherein each alkyl, heterocycloalkyl and cycloalkyl is optionally substituted with one or more substituents independently selected from hydroxy, halo, alkyl, acyl and alkoxy; ‘m’ is an integer from 0 to 5; ‘n’ is an integer from 0 to 3; ‘j’ is an integer from 0 to 4; and ‘k’ is an integer from 0 to 2. In another embodiment, the present application provides compounds of formula (I-1), wherein, W₁ is CH₂, NH or O; X1 and X2 are each independently CH, N, NRx, O or S; X3, X4 and X5 are each independently CH or N; R_x is hydrogen or alkyl; R₁ at each occurrence is independently alkyl, alkenyl, alkynyl, halo, cyano, amino, nitro, -OR1a, -C(O)R1b or cycloalkyl; wherein each of alkyl, alkenyl, alkynyl and cycloalkyl is optionally substituted with one or more substituents independently selected from halo, hydroxy and alkoxy; R2 and R2' are each independently hydrogen or alkyl; R3 is hydrogen or alkyl; R₄ at each occurrence is independently alkyl, alkenyl, alkynyl, halo, cyano, amino, nitro, -OR4a, -C(O)R4b, or cycloalkyl; wherein each of alkyl, alkenyl, alkynyl and cycloalkyl is optionally substituted with one or more substituents independently selected from hydroxy, halo and alkoxy; each R_1a and R_4a is independently hydrogen, alkyl, haloalkyl, cycloalkyl or heterocycloalkyl; R5 at each occurrence is independently halo, alkyl, haloalkyl, alkoxy or -C(O)R5a; each R1b, R4b and R5a is independently hydrogen, alkyl, amino, alkylamino, hydroxy, haloalkyl, cycloalkyl or heterocycloalkyl; R6 is alkyl,heterocycloalkyl or -C(O)R6c; wherein each alkyl and heterocycloalkyl is optionally substituted with one or more substituents independently selected from hydroxy, - NR_6aR_6b,halo and cycloalkyl, wherein the cycloalkyl is optionally substituted with one or more substituents independently selected from hydroxy, halo, alkyl, acyl and alkoxy; each R6a and R6b is independently hydrogen, alkyl, acyl or alkylsulfonyl; R_6c is independently alkyl, heterocycloalkyl or cycloalkyl, wherein each alkyl, heterocycloalkyl and cycloalkyl is optionally substituted with one or more substituents independently selected from hydroxy, halo, alkyl, acyl and alkoxy; ‘m’ is an integer from 0 to 5; ‘n’ is an integer from 0 to 3; ‘j’ is an integer from 0 to 4; and ‘k’ is an integer from 0 to 2. In another embodiment, the present application provides compounds of formula (I-1), or a pharmaceutically acceptable salt or a stereoisomer thereof; wherein, W₁ is C, N or O; X₁ and X₂ are each independently CH, N, NR_x, O or S; X3, X4 and X5 are each independently CH or N; Rx is hydrogen or (C1-C6)alkyl; R₁ at each occurrence is independently (C₁-C₆)alkyl, (C₂-C₆)alkenyl, (C₂-C₆)alkynyl, halo, cyano, amino, nitro, -OR1a, -C(O)R1b or (C3-C6)cycloalkyl; wherein each of alkyl, alkenyl, alkynyl and cycloalkyl is optionally substituted with one or more substituents independently selected from halo, hydroxy and (C₁-C₆)alkoxy; R₂ and R₂' are each independently hydrogen or (C₁-C₆)alkyl; R3 is hydrogen or (C1-C6)alkyl; R4 at each occurrence is independently (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, halo, cyano, amino, nitro, -OR4a, -C(O)R4b, or (C3-C6)cycloalkyl; wherein each of alkyl, alkenyl, alkynyl and cycloalkyl is optionally substituted with one or more substituents independently selected from hydroxy, halo and (C1-C6)alkoxy; each R1a and R4a is independently hydrogen, (C1-C6)alkyl, (C1-C6)haloalkyl, (C3-C6) cycloalkyl or (C₃-C₆)heterocycloalkyl; R₅ at each occurrence is independently halo, (C₁-C₆)alkyl, (C₁-C₆)haloalkyl, (C₁-C₆)alkoxy or -C(O)R5a; each R_1b, R_4b and R_5a is independently hydrogen, (C₁-C₆)alkyl, amino, (C₁- C₆)alkylamino, hydroxy, (C₁-C₆)haloalkyl, (C₃-C₆)cycloalkyl or (C₃-C₆)heterocycloalkyl; R6 is (C1-C10)alkyl, (C3-C6)heterocycloalkyl or -C(O)R6c; wherein each alkyl and heterocycloalkyl is optionally substituted with one or more substituents independently selected from hydroxy, -NR_6aR_6b, halo and (C₃-C₆)cycloalkyl, wherein the (C₃-C₆)cycloalkyl is optionally substituted with one or more substituents independently selected from hydroxy, halo, (C1-C6)alkyl, acyl and (C1-C6)alkoxy; each R_6a and R_6b is independently hydrogen, (C₁-C₆)alkyl, acyl or (C₁-C₆)alkylsulfonyl; R_6c is independently (C₁-C₆)alkyl, (C₃-C₆)heterocycloalkyl or (C₃-C₆)cycloalkyl, wherein each (C1-C6)alkyl, (C3-C6)heterocycloalkyl and (C3-C6)cycloalkyl is optionally substituted with one or more substituents independently selected from hydroxy, halo, (C₁-C₆) alkyl, acyl and (C₁-C₆)alkoxy; ‘m’ is an integer from 0 to 5; ‘n’ is an integer from 0 to 3; ‘j’ is an integer from 0 to 4; and ‘k’ is an integer from 0 to 2. In another embodiment, the present application provides compounds of formula (I),

or a pharmaceutically acceptable salt or a stereoisomer thereof . In another embodiment, the present application provides compounds of formula (I), or a pharmaceutically acceptable salt or a stereoisomer thereof; wherein, X1 and X2 are each independently CH, N, NRx, O or S; X3, X4 and X5 are each independently CH or N; provided that, when X₁ is CH or N, X₂ is NR_x, O or S; and when X₂ is CH or N, X₁ is NR_x, O or S; Rx is hydrogen or alkyl; R₁ at each occurrence is independently alkyl, alkenyl, alkynyl, halo, cyano, amino, nitro, -OR_1a, -C(O)R_1b or cycloalkyl; wherein each of alkyl, alkenyl, alkynyl, and cycloalkyl is optionally substituted with one or more substituents independently selected from halo, hydroxy and alkoxy; R₂ and R₂' are each independently hydrogen or alkyl; R3 is hydrogen or alkyl; R4 at each occurrence is independently alkyl, alkenyl, alkynyl, halo, cyano, amino, nitro, -OR_4a, -C(O)R_4b, or cycloalkyl; wherein each of alkyl, alkenyl, alkynyl, and cycloalkyl is optionally substituted with one or more substituents independently selected from hydroxy, halo and alkoxy; each R_1a and R_4a is independently hydrogen, alkyl, haloalkyl, cycloalkyl or heterocycloalkyl; R5 at each occurrence is independently halo, alkyl, haloalkyl, alkoxy or -C(O)R5a; each R1b, R4b and R5a is independently hydrogen, alkyl, amino, alkylamino, hydroxy, haloalkyl, cycloalkyl, or heterocycloalkyl; R₆ is alkyl or heterocycloalkyl; wherein each alkyl and heterocycloalkyl is optionally substituted with one or more substituents independently selected from hydroxy, -NR6aR6b and halo; each R_6a and R_6b is independently hydrogen, alkyl, acyl or alkylsulfonyl; ‘m’ is an integer from 0 to 5; ‘n’ is an integer from 0 to 3; ‘j’ is an integer from 0 to 4; and ‘k’ is an integer from 0 to 2. In another embodiment of the present application, it provides compounds of formula (IA-1), (IB-1), (IC-1), (ID-1), (IE-1), (IF-1) & (IG-1):

, or a pharmaceutically acceptable salt or a stereoisomer thereof; wherein ‘p’ is an integer from 1 to 8. In another embodiment of the present application, it provides compounds of formula (IA),

or a pharmaceutically acceptable salt or a stereoisomer thereof. In another embodiment of the present application, it provides compounds of formula (IB), or a pharmaceutically acceptable salt or a stereoisomer thereof. In another embodiment of the present application, it provides compounds of formula

or a pharmaceutically acceptable salt or a stereoisomer thereof. In another embodiment of the present application, it provides compounds of formula (ID),

or a pharmaceutically acceptable salt or a stereoisomer thereof. In another embodiment of the present application, it provides compounds of formula

wherein, X₁ is NR_x, O or S; or a pharmaceutically acceptable salt or a stereoisomer thereof. In another embodiment of the present application, it provides compounds of formula (IF),

or a pharmaceutically acceptable salt or a stereoisomer thereof; wherein p is an integer from 1 to 8. In another embodiment of the present application, it provides compounds of formula (IG),

or a pharmaceutically acceptable salt or a stereoisomer thereof. In one embodiment of the present application, it provides compounds of formula (I-1),

represents the point of attachment with azetidine ring. In one embodiment, the ring represented

represents the point of attachment with azetidine ring.

represents the point of attachment with azetidine ring.

wherein the asterisk mark represents the point of attachment with azetidine ring.

In one embodiment, X1 is NRx, O or S. In one embodiment, X₁ is O or S. In one embodiment, X₁ is O. In one embodiment, X1 is S. In one embodiment, X2 is CH, N or NRx. In one embodiment, X₂ is CH or N. In one embodiment, X2 is N. In one embodiment, X1 is NRx, O or S, and X2 is CH or N. In one embodiment, X1 is O or S, and X2 is N. In one embodiment, X₁ is N and X₂ is O. In one embodiment, X1 is O and X2 is N. In one embodiment, X1 is S and X2 is N. In one embodiment, R₁ at each occurrence is halo. In one embodiment, R₁ at each occurrence is chloro. In one embodiment, R2 is alkyl and R2' is hydrogen. In one embodiment, R3 is hydrogen. In one embodiment, R₄ at each occurrence is selected from halo, alkyl and -OR_4a. In one embodiment, R4 at each occurrence is selected from halo and alkyl. In one embodiment, R4 at each occurrence is halo. In one embodiment, R₆ is alkyl; wherein alkyl is optionally substituted with one or more substituents independently selected from hydroxy, -NR6aR6b and halo. In one embodiment, R6 is alkyl; wherein the alkyl is substituted with hydroxy. In one embodiment, R₆ is hydroxyalkyl. In one embodiment, X₁ and X₂ are each independently N, O or S; X3, X4 and X5 are each CH or N; R1 at each occurrence independently is alkyl or halo; R₂ is alkyl and R₂’ is hydrogen; R3 is hydrogen; R4 at each occurrence independently is alkyl, halo, cyano or -OR4a; wherein the alkyl is substituted with one or more halo; R_4a is alkyl or haloalkyl; R5 at each occurrence is independently halo, alkyl, haloalkyl; R6 is alkyl; wherein, the alkyl is independently substituted with one or more hydroxy or halo; ‘m’ is an integer from 0 to 2; ‘n’ is an integer from 0 to 2; ‘j’ is 0 to 2; and ‘k’ is 1. In one embodiment, X₁ and X₂ are each independently N, O or S; X3, X4 and X5 are each CH; R₁ at each occurrence independently is alkyl or halo; R₂ is alkyl and R₂' is hydrogen; R3 is hydrogen; R4 at each occurrence independently is unsubstituted or substituted alkyl, halo, cyano or -OR_4a; wherein the substituent is selected from one or more halo; R4a is alkyl or haloalkyl; R5 at each occurrence is independently halo, alkyl or haloalkyl; R₆ is unsubstituted or substituted alkyl; wherein, the substituent is independently selected from one or more hydroxy and halo; ‘m’ is an integer from 0 to 2; ‘n’ is an integer from 0 to 2; ‘j’ is 0; and ‘k’ is 1. In one embodiment, j is 1 or 2. In one embodiment, j is 0. In one embodiment, k is 0. In one embodiment, k is 1. In one embodiment, m is 2. In one embodiment, n is 0. In one embodiment, n is 1. In certain embodiments, the present application provides a compound selected from: Comp. No. IUPAC name 1 2-((R)-3-(1-(6-chloro-7-(((R)-1-(2,4-dichlorophenyl)ethyl)amino)benzo[d]oxazol- 2-yl)azetidin-3-yl)piperidin-1-yl)ethan-1-ol; 2 2-((R)-3-(1-(7-(((R)-1-(2,4-dichlorophenyl)ethyl)amino)benzo[d]thiazol-2- yl)azetidin-3-yl)piperidin-1-yl)ethan-1-ol; 3 2-((R)-3-(1-(6-Fluoro-7-(((R)-1-(2,4-dichlorophenyl)ethyl)amino)benzo[d]thiazol- 2-yl)azetidin-3-yl)piperidin-1-yl)ethan-1-ol; 4 2-((R)-3-(1-(7-(((R)-1-(2,4-dichlorophenyl)ethyl)amino)benzo[d]oxazol-2- yl)azetidin-3-yl)piperidin-1-yl)ethan-1-ol; 5 2-((R)-3-(1-(7-(((R)-1-(2,4-dichlorophenyl)ethyl)amino)-6-fluorobenzo[d]oxazol- 2-yl)azetidin-3-yl)piperidin-1-yl)ethan-1-ol; 6 2-((R)-3-(1-(5-chloro-7-(((R)-1-(2,4-dichlorophenyl)ethyl)amino)benzo[d]oxazol- 2-yl)azetidin-3-yl)piperidin-1-yl)ethan-1-ol; 7 2-((R)-3-(1-(7-(((R)-1-(2,4-dichlorophenyl)ethyl)amino)-5-methylbenzo[d]oxazol- 2-yl)azetidin-3-yl)piperidin-1-yl)ethan-1-ol; 8 2-((R)-3-(1-(6-chloro-7-(((R)-1-(2,4-dichlorophenyl)ethyl)amino)-5- methylbenzo[d]oxazol-2-yl)azetidin-3-yl)piperidin-1-yl)ethan-1-ol; 9 2-((R)-3-(1-(7-(((R)-1-(2,4-dichlorophenyl)ethyl)amino)-6-methylbenzo[d]oxazol- 2-yl)azetidin-3-yl)piperidin-1-yl)ethan-1-ol; 10 2-((R)-3-(1-(6-chloro-7-(((R)-1-(2,4-dichlorophenyl)ethyl)amino)benzo[d]thiazol- 2-yl)azetidin-3-yl)piperidin-1-yl)ethan-1-ol; N-(2-((R)-3-(1-(6-chloro-7-(((R)-1-(2,4- 11 dichlorophenyl)ethyl)amino)benzo[d]oxazol-2-yl)azetidin-3-yl)piperidin-1- yl)ethyl)acetamide; 12 6-chloro-N-((R)-1-(2,4-dichlorophenyl)ethyl)-2-(3-((R)-1-(tetrahydro-2H-pyran-4- yl)piperidin-3-yl)azetidin-1-yl)benzo[d]oxazol-7-amine; 13 4-((R)-3-(1-(6-chloro-7-(((R)-1-(2,4-dichlorophenyl)ethyl)amino)benzo[d]oxazol- 2-yl)azetidin-3-yl)piperidin-1-yl)tetrahydro-2H-thiopyran 1,1-dioxide; N-(2-((R)-3-(1-(6-chloro-7-(((R)-1-(2,4- 14 dichlorophenyl)ethyl)amino)benzo[d]oxazol-2-yl)azetidin-3-yl)piperidin-1- yl)ethyl)methanesulfonamide; 1-((R)-3-(1-(6-chloro-7-(((R)-1-(2,4-dichlorophenyl)ethyl)amino)benzo[d]oxazol- 2-yl)azetidin-3-yl)piperidin-1-yl)-2-methylpropan-2-ol; 1-(((R)-3-(1-(6-chloro-7-(((R)-1-(2,4-dichlorophenyl)ethyl)amino)benzo[d]oxazol- 2-yl)azetidin-3-yl)piperidin-1-yl)methyl)cyclopropan-1-ol; 2-((R)-3-(1-(7-(((R)-1-(2,4-dichlorophenyl)ethyl)amino)thiazolo[4,5-d]pyrimidin- 2-yl)azetidin-3-yl)piperidin-1-yl)ethan-1-ol; 2-(2-(1-(7-(((R)-1-(2,4-dichlorophenyl)ethyl)amino)-6-fluorobenzo[d]thiazol-2- yl)azetidin-3-yl)morpholino)ethan-1-ol; 2-((R)-2-(1-(7-(((R)-1-(2,4-dichlorophenyl)ethyl)amino)-6-fluorobenzo[d]thiazol- 2-yl)azetidin-3-yl)morpholino)ethan-1-ol (Isomer-1 of compound 18); 2-((S)-2-(1-(7-(((R)-1-(2,4-dichlorophenyl)ethyl)amino)-6-fluorobenzo[d]thiazol- 2-yl)azetidin-3-yl)morpholino)ethan-1-ol (Isomer-2 of compound 18); 2-((R)-3-(1-(7-(((R)-1-(2,4-dichlorophenyl)ethyl)amino)-6-fluorobenzo[d]thiazol- 2-yl)azetidin-3-yl)piperidin-1-yl)propan-1-ol; (R)-2-((R)-3-(1-(7-(((R)-1-(2,4-dichlorophenyl)ethyl)amino)-6- fluorobenzo[d]thiazol-2-yl)azetidin-3-yl)piperidin-1-yl)propan-1-ol (Isomer-1 of compound 21); (S)-2-((R)-3-(1-(7-(((R)-1-(2,4-dichlorophenyl)ethyl)amino)-6- fluorobenzo[d]thiazol-2-yl)azetidin-3-yl)piperidin-1-yl)propan-1-ol (Isomer-2 of compound 21); 1-((R)-3-(1-(7-(((R)-1-(2,4-dichlorophenyl)ethyl)amino)-6-fluorobenzo[d]thiazol- 2-yl)azetidin-3-yl)piperidin-1-yl)-2-methylpropan-2-ol; 1-(((R)-3-(1-(7-(((R)-1-(2,4-dichlorophenyl)ethyl)amino)-6-fluorobenzo[d]thiazol- 2-yl)azetidin-3-yl)piperidin-1-yl)methyl)cyclopropan-1-ol; ((R)-3-(1-(7-(((R)-1-(2,4-dichlorophenyl)ethyl)amino)-6-fluorobenzo[d]thiazol-2- yl)azetidin-3-yl)piperidin-1-yl)(1-hydroxycyclopropyl)methanone; 2-(5-(1-(7-(((R)-1-(2,4-dichlorophenyl)ethyl)amino)-6-fluorobenzo[d]thiazol-2- yl)azetidin-3-yl)-2-methylpiperidin-1-yl)ethan-1-ol; 2-((2R,5R)-5-(1-(7-(((R)-1-(2,4-dichlorophenyl)ethyl)amino)-6- fluorobenzo[d]thiazol-2-yl)azetidin-3-yl)-2-methylpiperidin-1-yl)ethan-1-ol (Isomer-1 of compound 27); 2-((2S,5R)-5-(1-(7-(((R)-1-(2,4-dichlorophenyl)ethyl)amino)-6- fluorobenzo[d]thiazol-2-yl)azetidin-3-yl)-2-methylpiperidin-1-yl)ethan-1-ol (Isomer-2 of compound 27); (R)-2-(4-(1-(7-((1-(2,4-dichlorophenyl)ethyl)amino)-6-fluorobenzo[d]thiazol-2- yl)azetidin-3-yl)piperidin-1-yl)ethan-1-ol; 2-((R)-3-(1-(7-(((R)-1-(2,4-dichlorophenyl)ethyl)amino)-6-fluorothiazolo[4,5- b]pyridin-2-yl)azetidin-3-yl)piperidin-1-yl)ethan-1-ol; 2-((3R)-3-(1-(7-(((R)-1-(2,4-dichlorophenyl)ethyl)amino)-6-fluorobenzo[d]thiazol- 2-yl)azetidin-3-yl)-2,6-dimethylpiperidin-1-yl)ethan-1-ol; 2-((R)-3-(1-(7-(((R)-1-(2,4-dichlorophenyl)ethyl)amino)-6- methoxybenzo[d]oxazol-2-yl)azetidin-3-yl)piperidin-1-yl)ethan-1-ol; 2-((R)-3-(1-(7-(((R)-1-(2,4-dichlorophenyl)ethyl)amino)-6- (difluoromethoxy)benzo[d]oxazol-2-yl)azetidin-3-yl)piperidin-1-yl)ethan-1-ol; 2-((R)-3-(1-(7-(((R)-1-(2,4-dichlorophenyl)ethyl)amino)-6- (trifluoromethoxy)benzo[d]oxazol-2-yl)azetidin-3-yl)piperidin-1-yl)ethan-1-ol; 2-((R)-3-(1-(7-(((R)-1-(2,4-dichlorophenyl)ethyl)amino)-6- (trifluoromethyl)benzo[d]oxazol-2-yl)azetidin-3-yl)piperidin-1-yl)ethan-1-ol; 2-((R)-3-(1-(4-(((R)-1-(2,4-dichlorophenyl)ethyl)amino)oxazolo[5,4-c]pyridin-2- yl)azetidin-3-yl)piperidin-1-yl)ethan-1-ol; 2-((R)-3-(1-(7-(((R)-1-(2,4-dichlorophenyl)ethyl)amino)oxazolo[4,5-c]pyridin-2- yl)azetidin-3-yl)piperidin-1-yl)ethan-1-ol; 2-((R)-3-(1-(7-(((R)-1-(2,4-dichlorophenyl)ethyl)amino)oxazolo[4,5-b]pyridin-2- yl)azetidin-3-yl)piperidin-1-yl)ethan-1-ol; 2-((R)-3-(1-(6-chloro-7-(((R)-1-(2,4-dichlorophenyl)ethyl)amino)oxazolo[4,5- b]pyridin-2-yl)azetidin-3-yl)piperidin-1-yl)ethan-1-ol; 2-((R)-3-(1-(6-chloro-7-(((R)-1-(2,4-dichlorophenyl)ethyl)amino)-5- methyloxazolo[4,5-b]pyridin-2-yl)azetidin-3-yl)piperidin-1-yl)ethan-1-ol; 2-((R)-3-(1-(6-chloro-7-(((R)-1-(2,4-dichlorophenyl)ethyl)amino)benzofuran-2- yl)azetidin-3-yl)piperidin-1-yl)ethan-1-ol; 2-((R)-3-(1-(6-chloro-7-(((R)-1-(2,4-dichlorophenyl)ethyl)amino)-1-methyl-1H- indol-2-yl)azetidin-3-yl)piperidin-1-yl)ethan-1-ol; (R)-1-(2,4-dichlorophenyl)ethyl)amino)-2-(3-((R)-1-(2-hydroxyethyl)piperidin-3- yl)azetidin-1-yl)-N,N-dimethylbenzo[d]oxazole-6-carboxamide; 7-(((R)-1-(2,4-dichlorophenyl)ethyl)amino)-2-(3-((R)-1-(2- hydroxyethyl)piperidin-3-yl)azetidin-1-yl)benzo[d]oxazole-6-carboxamide; 7-(((R)-1-(2,4-dichlorophenyl)ethyl)amino)-2-(3-((R)-1-(2- hydroxyethyl)piperidin-3-yl)azetidin-1-yl)benzo[d]oxazole-6-carbonitrile; 3-((R)-3-(1-(6-chloro-7-(((R)-1-(2,4-dichlorophenyl)ethyl)amino)benzo[d]oxazol- 2-yl)azetidin-3-yl)pyrrolidin-1-yl)propan-1-ol; 48 2-((R)-3-(1-(7-(((R)-1-(2,4-dichlorophenyl)ethyl)amino)-6- (difluoromethyl)benzo[d]oxazol-2-yl)azetidin-3-yl)piperidin-1-yl)ethan-1-ol; 49 2-((R)-3-(1-(6-chloro-7-(((R)-1-(2,4-dichlorophenyl)ethyl)amino)benzo[d]oxazol- 2-yl)azetidin-3-yl)pyrrolidin-1-yl)ethan-1-ol; 1-(7-(((R)-1-(2,4-dichlorophenyl)ethyl)amino)-2-(3-((R)-1-(2- 50 hydroxyethyl)piperidin-3-yl)azetidin-1-yl)benzo[d]oxazol-6-yl)-2,2,2- trifluoroethan-1-ol; 51 1-(7-(((R)-1-(2,4-dichlorophenyl)ethyl)amino)-2-(3-((R)-1-(2- hydroxyethyl)piperidin-3-yl)azetidin-1-yl)benzo[d]oxazol-6-yl)ethan-1-ol; and 52 2-((R)-3-(1-(7-(((R)-1-(2,4-dichlorophenyl)ethyl)amino)-6- (hydroxymethyl)benzo[d]oxazol-2-yl)azetidin-3-yl)piperidin-1-yl)ethan-1-ol; or a pharmaceutically acceptable salt thereof or a stereoisomer thereof. In certain embodiments, the present disclosure provides a pharmaceutical composition comprising a compound of formula (I-1), or a pharmaceutically acceptable salt thereof or a stereoisomer thereof as described herein and at least one pharmaceutically acceptable excipient (such as a pharmaceutically acceptable carrier or diluent). Preferably, the pharmaceutical composition comprises a therapeutically effective amount of at least one compound described herein. The compounds described in the present disclosure may be associated with a pharmaceutically acceptable excipient (such as a carrier or a diluent) or be diluted by a carrier or enclosed within a carrier which can be in the form of a capsule, sachet, paper or other container. In yet another embodiment, the compounds of the present disclosure are CCR4 modulators. In yet another embodiment, the compound of formula (I-1) is a CCR4 modulator. In another embodiment, the present disclosure provides pharmaceutical composition for use in treating and/or preventing a disease and/or disorder responsive to the modulation of CCR4 activity. In another embodiment, the present disclosure provides pharmaceutical composition comprising a compound of formula (I-1), or a pharmaceutically acceptable salt or a stereoisomer thereof, for use in the manufacture of a medicament for treating and/or preventing a disease and/or disorder responsive to the modulation of CCR4 activity. In another embodiment, the present disclosure provides a pharmaceutical composition comprising a compound of formula (I-1), or a pharmaceutically acceptable salt or a stereoisomer thereof and at least one pharmaceutically acceptable carrier or excipient. In an embodiment, the present disclosure provides pharmaceutical composition comprising the compound of formula (I-1), for use in treating a subject suffering from a disease or condition associated with CCR4. In an embodiment, the present disclosure provides pharmaceutical composition comprising the compound of formula (I-1), for use in the manufacture of a medicament for treating a subject suffering from a disease or condition associated with CCR4. The compounds of the disclosure are typically administered in the form of a pharmaceutical composition. Such compositions can be prepared using procedures well known in the pharmaceutical art and comprise at least one compound of the present disclosure. The pharmaceutical composition of the present disclosure comprises one or more compounds described herein and one or more pharmaceutically acceptable excipients. Typically, the pharmaceutically acceptable excipients are approved by regulatory authorities or are generally regarded as safe for human or animal use. The pharmaceutically acceptable excipients include, but are not limited to, carriers, diluents, glidants and lubricants, preservatives, buffering agents, chelating agents, polymers, gelling agents, viscosifying agents, solvents and the like. The pharmaceutical composition can be administered by oral, parenteral or inhalation routes. Examples of the parenteral administration include administration by injection, percutaneous, transmucosal, transnasal and transpulmonary administrations. Examples of suitable carriers include, but are not limited to, water, salt solutions, alcohols, polyethylene glycols, peanut oil, olive oil, gelatin, lactose, terra alba, sucrose, dextrin, magnesium carbonate, sugar, amylose, magnesium stearate, talc, agar, pectin, acacia, stearic acid, lower alkyl ethers of cellulose, silicic acid, fatty acids, fatty acid amines, fatty acid monoglycerides and diglycerides, fatty acid esters and polyoxyethylene. The pharmaceutical composition may also include one or more pharmaceutically acceptable auxiliary agents, wetting agents, suspending agents, preserving agents, buffers, sweetening agents, flavouring agents, colorants or any combination of the foregoing. The pharmaceutical compositions may be in conventional forms, for example, tablets, capsules, solutions, suspensions, injectables or products for topical application. Further, the pharmaceutical composition of the present disclosure may be formulated to provide desired release profile. Administration of the compounds of the disclosure, in pure form or in an appropriate pharmaceutical composition, can be carried out using any of the accepted routes of administration of pharmaceutical compositions. The route of administration may be any route which effectively transports the active compound of the present disclosure to the appropriate or desired site of action. Suitable routes of administration include, but are not limited to, oral, nasal, buccal, dermal, intradermal, transdermal, parenteral, rectal, subcutaneous, intravenous, intraurethral, intramuscular or topical. Solid oral formulations include, but are not limited to, tablets, capsules (soft or hard gelatin), dragees (containing the active ingredient in powder or pellet form), troches and lozenges. Liquid formulations include, but are not limited to, syrups, emulsions and sterile injectable liquids, such as suspensions or solutions. Topical dosage forms of the compounds include ointments, pastes, creams, lotions, powders, solutions, eye or ear drops, impregnated dressings and may contain appropriate conventional additives such as preservatives, solvents to assist drug penetration. The pharmaceutical compositions of the present disclosure may be prepared by conventional techniques known in literature. Suitable doses of the compounds for use in treating the diseases or disorders described herein can be determined by those skilled in the relevant art. Therapeutic doses are generally identified through a dose ranging study in humans based on preliminary evidence derived from the animal studies. Doses must be sufficient to result in a desired therapeutic benefit without causing unwanted side effects. Mode of administration, dosage forms and suitable pharmaceutical excipients can also be well used and adjusted by those skilled in the art. All changes and modifications are envisioned within the scope of the present disclosure. In one embodiment, the compounds as disclosed in the present disclosure are formulated for pharmaceutical administration. Yet another embodiment of the present disclosure provides use of the compounds as disclosed in the present application in the treatment and prevention of diseases and/or disorder responsive to the modulation of CCR4 activity. Yet another embodiment of the present disclosure provides use of the compound or a pharmaceutically acceptable salt thereof, in treating and/or preventing a disease for which the symptoms thereof are treated, improved, diminished and/or prevented by modulation of CCR4. According to yet another embodiment, the CCR4 mediated disorder and/or disease or condition is cancer or an inflammatory disease or disorder. According to yet another embodiment, the CCR4 mediated disorder and/or disease or condition is cancer. In yet another aspect of an embodiment, the cancer is colon cancer, pancreatic cancer, intestinal cancer, breast cancer, lung cancer, gastric cancer, liver cancer or colorectal cancer. In yet another aspect of an embodiment, the cancer is colon cancer, pancreatic cancer or intestinal cancer. According to yet another embodiment, the CCR4 mediated disorder and/or disease or condition is an inflammatory disease or disorder. In yet another aspect of an embodiment, the inflammatory disease or disorder is dermatitis. In yet another aspect of an embodiment, the inflammatory disease or disorder is atopic dermatitis or contact dermatitis. In yet another aspect of an embodiment, the inflammatory disease or disorder is atopic dermatitis. In yet another aspect of an embodiment, the inflammatory disease or disorder is contact dermatitis. In yet another aspect of an embodiment, the inflammatory disease or disorder is prurigo nodularis. In yet another aspect of an embodiment, the inflammatory disease or disorder is related to but not limited to Th2-associated inflammation in various mucosal barriers including lung and upper respiratory tissues. Accordingly, the present disclosure provides compounds for the use in respiratory allergies or for asthma or for chronic rhinosinusitis with or without nasal polyposis (CRSwNP). In yet another aspect of an embodiment, the inflammatory disease or disorder is related to but not limited to Th2-associated inflammation in various mucosal barriers including upper and lower alimentary tract tissues. Accordingly, the present disclosure provides compounds for the use in eosinophilic esophagitis (EoE) as well as but not limited to inflammatory bowel disease (IBD). In yet another embodiment, the present disclosure provides compounds for treatment of ulcerative colitis (UC) including but not limited to Th2-associated UC. According to yet another embodiment, the present disclosure provides compound of formula (I-1) for use in the treatment of cancer. According to yet another embodiment, the subject is a mammal including human. According to yet another embodiment, the present disclosure provides compounds or pharmaceutically acceptable salts or stereoisomers thereof, for use as a medicament. According to yet another embodiment, the disclosure provides the use of the compounds of the present disclosure in the manufacture of a medicament. According to yet another embodiment, the present disclosure provides compounds or pharmaceutically acceptable salts or stereoisomers thereof, for use in the treatment of cancer or an inflammatory disease or disorder. In yet another aspect of an embodiment, the cancer is colon cancer, pancreatic cancer, intestinal cancer, breast cancer, lung cancer, gastric cancer, liver cancer or colorectal cancer. In yet another aspect of an embodiment, the cancer is skin cancer including but not limited to melanoma or invasive adenocarcinoma. In yet another embodiment, the present disclosure provides compounds for use in the treatment of haematological cancers including but not limited to T cell lymphomas and leukaemia. The present disclosure further provides compounds for use in established HTLV-1 viral induced T cell leukaemia and lymphoma or for the prevention of leukaemogenesis in HTLV-1 positive patients. In yet another embodiment, the present disclosure provides compounds for use in the treatment and/or prevention of CCR4 activity that promotes metastasis due to migration of tumour cells expressing CCR4 to remote target organs that express CCL17 or CCL22 through lymphatics or blood circulation. Accordingly, the present disclosure provides compounds for use to inhibit metastasis to secondary lymphoid structures including but not limited to draining lymph nodes, downstream lymph nodes, thymus, lung, liver, bone marrow, skin, intestines, kidney and brain. In yet another embodiment, the present disclosure provides compounds for use in the treatment and/or prevention of CCR4 activity that promotes migration of leukaemia cells to sites resulting in development of cutaneous or thymic lymphomas through recruitment of immunosuppressive regulatory T-cells (Treg) cells that can inhibit tumor immunity and clearance. According to yet another embodiment, the disclosure provides the use of the compounds of the present disclosure in the manufacture of a medicament for the treatment of diseases and/or disorder responsive to the modulation of CCR4 activity. According to yet another embodiment, the disclosure provides a compound or a pharmaceutical acceptable salt or a stereoisomer thereof, for use in the treatment of CCR4 mediated disease or disorder. In yet another embodiment, the disclosure provides the use of the compounds of the present disclosure in the manufacture of a medicament for the treatment of cancer or an inflammatory disease or disorder. In yet another embodiment, the disclosure provides the use of the compounds of the present disclosure in the manufacture of a medicament for the treatment of cancer. In yet another embodiment, the disclosure provides the use of the compounds of the present disclosure in the manufacture of a medicament for the treatment of cancer wherein the cancer is colon cancer, pancreatic cancer, intestinal cancer, breast cancer, lung cancer, gastric cancer, liver cancer or colorectal cancer. In yet another embodiment, the disclosure provides the use of the compounds of the present disclosure in the manufacture of a medicament for the treatment of CCR4-mediated disease or disorder. In yet another embodiment, the disclosure provides the use of the compounds of the present disclosure in the manufacture of a medicament for the treatment of inflammatory disease or disorder. In yet another embodiment, the disclosure provides the use of the compounds of the present disclosure in the manufacture of a medicament for the treatment of inflammatory disease or disorder wherein the inflammatory disease or disorder is dermatitis. In yet another embodiment, the disclosure provides the use of the compounds of the present disclosure in the manufacture of a medicament for the treatment of inflammatory disease or disorder wherein the inflammatory disease or disorder is atopic dermatitis or contact dermatitis. In yet another embodiment, the present application provides compounds for use as a medicament for treating a subject suffering from diseases and/or disorder responsive to the modulation of CCR4 activity. In yet another embodiment, the present application provides compounds for use in the manufacture of a medicament for treating a subject suffering from diseases and/or disorder responsive to the modulation of CCR4 activity. In yet another embodiment, the disclosure provides compounds of the present disclosure for use in the manufacture of a medicament for the treatment of cancer. In yet another embodiment, the disclosure provides compounds of the present disclosure for use in the manufacture of a medicament for the treatment of inflammation. In yet another embodiment, the disclosure provides compounds of the present disclosure for use in the manufacture of a medicament for the treatment of cancer wherein the cancer is colon cancer, pancreatic cancer, intestinal cancer, breast cancer, lung cancer, gastric cancer, liver cancer or colorectal cancer. In yet another embodiment, the disclosure provides compounds of the present disclosure for use in the manufacture of a medicament for the treatment of inflammatory disease or disorder. In yet another embodiment, the disclosure provides compounds of the present disclosure for use in the manufacture of a medicament for the treatment of inflammatory disease or disorder wherein the inflammatory disease or disorder is dermatitis. In yet another embodiment, the disclosure provides compounds of the present disclosure for use in the manufacture of a medicament for the treatment of inflammatory disease or disorder wherein the inflammatory disease or disorder is atopic dermatitis or contact dermatitis. In yet another embodiment, the present disclosure comprises administering to the subject in need thereof a therapeutically effective amount of a compound of the present disclosure along with one or more additional chemotherapeutic agents independently selected from anti-proliferative agents, anti-cancer agents, immunosuppressant agents and pain- relieving agents. In yet another embodiment, the present disclosure comprises administering to the subject in need thereof a therapeutically effective amount of a compound of the present disclosure along with one or more additional anti-inflammatory agents. The method(s) of treatment of the present disclosure comprises administering a safe and effective amount of a compound of formula (I-1) or a pharmaceutically acceptable salt thereof to a patient (particularly a human) in need thereof. In certain embodiments, the present disclosure provides a method of treating diseases and/or disorder mediated by CCR4 in a subject comprising administering to the subject in need thereof a therapeutically effective amount of a compound of formula (I-1). In certain embodiments, the present disclosure provides a method of modulating CCR4 in a subject, comprising contacting CCR4 with a compound of formula (I-1), or a pharmaceutically acceptable salt thereof. A method of modulating CCR4 in a subject, comprising administering to the subject a therapeutically effective amount of a compound of formula (I-1), or a pharmaceutically acceptable salt thereof. In certain embodiments, the present disclosure provides a method of treating or preventing a disease or disorder mediated by CCR4, comprising administering to the subject in need thereof a therapeutically effective amount of a compound of formula (I-1), or a pharmaceutically acceptable salt thereof. In certain embodiments, the present disclosure provides a method of treating or preventing a disease or disorder mediated by CCR4, the disease or disorder is cancer or an inflammatory disease or disorder. According to certain foregoing embodiments, the present disclosure provides a method wherein the disease or disorder is inflammation. According to certain foregoing embodiments, the present disclosure provides a method wherein the inflammatory disease or disorder is dermatitis. According to certain foregoing embodiments, the present disclosure provides a method wherein the disease or disorder is atopic dermatitis or contact dermatitis. According to certain foregoing embodiments, the present disclosure provides a method wherein the disease or disorder is cancer. According to certain foregoing embodiments, the present disclosure provides a method wherein the cancer is colon cancer, pancreatic cancer, intestinal cancer, breast cancer, lung cancer, gastric cancer, liver cancer or colorectal cancer. According to certain foregoing embodiments, the present disclosure provides a method comprising administering to the subject in need thereof one or more chemotherapeutic agents or anti-inflammatory agents. Compounds of the disclosure are indicated both in the therapeutic and/or prophylactic treatment of the above-mentioned conditions. For the above-mentioned therapeutic uses the dosage administered will, of course, vary with the compound employed, the mode of administration, the treatment desired and the disorder or disease indicated. The compounds of the present disclosure may be used as single drug or as a pharmaceutical composition in which the compound is mixed with various pharmacologically acceptable materials. According to one embodiment, the compounds of the present disclosure can also contain unnatural proportions of atomic isotopes at one or more of the atoms that constitute such compounds. For example, the present disclosure also embraces isotopically-labeled variants of the present disclosure which are identical to those recited herein, but for the fact that one or more atoms of the compound are replaced by an atom having the atomic mass or mass number different from the predominant atomic mass or mass number usually found in nature for the atom. All isotopes of any particular atom or element as specified are contemplated within the scope of the compounds of the disclosure and their uses. Exemplary isotopes that can be incorporated in to compounds of the disclosure include isotopes of hydrogen, carbon, nitrogen, oxygen, phosphorous, sulfur, fluorine, chlorine and iodine, such as ²H (“D”), ³H, ¹¹C, ¹³C, ¹⁴C, ¹³N, ¹⁵N, ¹⁵O, ¹⁷O, ¹⁸O, ³²P, ³³P, ³⁵S, ¹⁸F, ³⁶Cl, ¹²³I and ¹²⁵I. Isotopically labeled compounds of the present disclosure can generally be prepared by following procedures analogous to those disclosed in the schemes and/or in the examples herein below, by substituting an isotopically labeled reagent for a non-isotopically labeled reagent. EXPERIMENTAL The present application provides methods for the preparation of compound of formula (I-1) according to the description provided herein using appropriate methods and/or materials. It is to be understood by those skilled in the art that known variations of the conditions and processes of the following procedures can be used to prepare these intermediates and compounds. Moreover, by utilizing the procedures described in detail, one of ordinary skill in the art can prepare additional compounds of the present disclosure. Following general guidelines apply to all experimental procedures described here. Until otherwise stated, experiments are performed under positive pressure of nitrogen, temperature described are the external temperature (i.e. oil bath temperature). Reagents and solvents received from vendors are used as such without any further drying or purification. Molarities mentioned here for reagents in solutions are approximate as it was not verified by a prior titration with a standard. All reactions are stirred under magnetic stir bar. Cooling to minus temperature was done by acetone / dry ice or wet ice / salts. Magnesium sulfate and sodium sulfate were used as solvent drying agent after reaction work up and are interchangeable. Removing of solvents under reduced pressure or under vacuum means distilling of solvents in rotary evaporator. Compounds of this disclosure may be made by synthetic chemical processes, examples of which are shown herein. It is meant to be understood that the order of the steps in the processes may be varied, that reagents, solvents and reaction conditions may be substituted for those specifically mentioned and that vulnerable moieties may be protected and deprotected, as necessary. The specifics of the process for preparing compounds of the present disclosure are detailed in the experimental section. The present disclosure shall be illustrated by means of some examples, which are not construed to be viewed as limiting the scope of the disclosure. Unless otherwise stated, work-up includes distribution of the reaction mixture between the organic and aqueous phases, separation of layers and drying the organic layer over anhydrous sodium sulphate, filtration and evaporation of the solvent. Purification, unless otherwise mentioned, includes purification by silica gel chromatographic techniques, generally using ethyl acetate/petroleum ether mixture of a suitable polarity as the mobile phase. Analysis for the compounds of the present disclosure unless mentioned, was conducted in general methods well known to a person skilled in the art. Having described the disclosure with reference to certain preferred embodiments, other embodiments will become apparent to one skilled in the art from consideration of the specification. The disclosure is further defined by reference to the following examples, describing in detail the analysis of the compounds of the disclosure. It will be apparent to those skilled in the art that many modifications, both to materials and methods, may be practiced without departing from the scope of the disclosure. Some of the intermediates were taken to next step based on TLC results, without further characterization, unless otherwise specified. Abbreviations: BoC2O- Boc anhydride; DIPA- diisopropylamine; NBS- N-Bromosuccinimide; DMF-N,N- Dimethylformamide; STAB- Sodium triacetoxyhydroborate; DCE- Dichloroethane; Ac2O- acetic anhydride; MsCl- Methanesulfonyl chloride; DHP-3,4-dihydro-2H-pyran; PTSA-p- Toluenesulfonic acid; PPTS-Pyridinium p-toluenesulfonate; DMP- Dess-martin’s periodinane; 1,2-DCE-1, 2-Dichloroethene; LDA-Lithium diisopropylamide; KOtBu- Potassium tert- butoxide; tBuOH- tert-Butyl alcohol; BH₃.THF- Borane in tetrahydrofuran; AcOH- Acetic acid; EDCl- 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide; HOBt- Hydroxybenzotriazole; NMM- N-methylmorpholine; TMSCl- Trimethylsilyl chloride; PtO2- Platinum dioxide; NaH- sodium hydride; nBuLi- n-Butyllithium; mCPBA- meta-Chloroperoxybenzoic acid; CsF- Cesium fluoride; Pd2dba3- Tris(dibenzylideneacetone)dipalladium; tBu-XPhos- 2-Di-t- butylphosphino-2',4',6'-triisopropyl-1,1'-biphenyl; ACN-Acetonitrile; EtOAc-Ethyl acetate; THF-Tetrahydrofuran; DCM-Dichloromethane; MeOH-Methanol; EtOH-Ethanol; DMSO- dimethyl sulfoxide; MeI-Methyl iodide; EtI-Ethyl iodide; TEA (or) Et₃N-Triethylamine; DIPEA- N,N-Diisopropylethylamine; K2CO3-Potassium carbonate; NaOAc-Sodium acetate; KOAc-Potassium acetate; NH4OH-Ammonium hydroxide; NH4Cl-Ammonium chloride; HATU-1-[Bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium 3-oxide hexafluorophosphate; DIPA - Diisopropylamine; EDCI; 1-Ethyl-3-(3- dimethylaminopropyl)carbodiimide; TFA-Trifluoroacetic acid; Pd(dppf)Cl2·DCM-[1,1′- Bis(diphenylphosphino)ferrocene]dichloropalladium(II), complex with dichloromethane; Pd(OAc)₂-Palladium(II) acetate; P(O-Tol)₃-Tri(o-tolyl)phosphine; Int-Intermediate; RT/rt- Room temperature; TLC-Thin layer chromatography; LC-MS-Liquid chromatography–mass spectrometry; HPLC-High performance liquid chromatography; DMSO-d₆-Deuterated dimethyl sulfoxide; Chloroform-d-Deuterated chloroform; NMR-Nuclear magnetic resonance, s-Singlet, d-Doublet, t-Triplet, q-Quartet, app. quint-Apparent quintet, dd-doublet of doublets, td-Triplet of doublets, SM-starting material, Int-Intermediate, Comp.-Compound, RT-Room temperature. Intermediates: Synthesis of 7-bromo-6-chlorobenzo[d]oxazole-2-thiol (I-1):

Step-1: Synthesis of tert-butyl (4-chloro-2-hydroxyphenyl)carbamate To the stirred solution of 2-amino-5-chlorophenol (5 g, 34.8 mmol) in THF (50 mL) was added Boc anhydride (11.4 g, 52.2 mmol) at 0 °C. The resulting reaction mixture was warmed to RT and stirred at the same temperature for 4h. After the completion of reaction, the reaction mixture was diluted with ice cold water, extracted with ethyl acetate and the two layers were separated. The organic layer was dried over Na2SO4, filtered and concentrated to get crude compound. The crude compound was purified by combi-flash chromatography using 10% ethyl acetate in hexane as an eluent to afford the pure intermediate- 1b (5 g, 58.9%). LC-MS: 242.0 [M-H]-. Step-2: Synthesis of tert-butyl (3-bromo-4-chloro-2-hydroxyphenyl)carbamate To the stirred solution of tert-butyl (4-chloro-2-hydroxyphenyl)carbamate (0.5 g, 2.052 mmol) in DCM (10 mL) was added diisopropylamine (0.441 g, 4.1 mmol) and NBS (0.29 g, 1.64 mmol) at 0 °C. The reaction mixture was warmed to RT and stirred for 4h. After the completion of reaction, the reaction mixture was quenched with saturated Aq. sodium thiosulphate, extracted with DCM and the layers were separated. The organic portion was dried over Na₂SO₄, filtered and concentrated to get the crude. The crude compound was purified by combi flash chromatograph using 5% ethyl acetate in hexane as an eluent afford the pure intermediate- 1c (0.2 g, 30.2%). LC-MS: 321.9 [M-H]-. Step-3: Synthesis of 6-amino-2-bromo-3-chlorophenol To the stirred solution of tert-butyl (3-bromo-4-chloro-2-hydroxyphenyl)carbamate (0.12 g, 0.37 mmol) in DCM (1 mL) was added 4M HCl in dioxane (1 mL) at 0 °C. Then the resulting reaction mixture was stirred at RT for 4h. After the completion of reaction, the reaction mixture was quenched with saturated aq. NaHCO3, extracted with ethyl acetate and the layers were separated. The organic layer was dried over Na2SO4, filtered and concentrated to afford the title intermediate-1d (0.1 g). LC-MS: 223.9 [M+H]⁺. Step-4: Synthesis of 7-bromo-6-chlorobenzo[d]oxazole-2-thiol To the stirred solution of 6-amino-2-bromo-3-chlorophenol (0.5 g, 2.24 mmol) in acetonitrile (10 mL) was added di(1H-imidazol-1-yl)methanethione (0.8 g, 4.49 mmol) at 0 °C. The resulting reaction mixture was warmed to RT and stirred at 85 °C for 4h. After the completion of reaction, the reaction mixture was cooled to RT, quenched with 1N HCl, extracted with ethyl acetate and the layers were separated. The organic layer was dried over Na2SO4, filtered and concentrated to afford the intermediate- I-1 (0.55 g). LC-MS: 263.8 [M-H]-. Synthesis of 7-bromobenzo[d]oxazole-2-thiol (I-2): To the stirred solution of 2-amino-6-bromophenol (3 g, 15.9 mmol) in methanol (50 mL) was added potassium ethyl xanthate (2.83 g, 17.8 mmol) at RT. Then the resulting reaction mixture was stirred at 65 °C for 7h. After the completion of reaction, the reaction mixture was cooled to RT, solvent was removed under vacuum pressure, the residue was dissolved in water and acidified with 1N HCl. The precipitated solid was filtered, washed with water. The residue thus obtained was dissolved using ethyl acetate, washed with water and the two layers were separated. The organic layer was dried over Na₂SO₄, filtered and concentrated under vacuo to get intermediate -I-2 as dark brown solid (2.36 g). This was used as such without further purification. LC-MS: 229.8 [M-H]-. The intermediates listed below in Table-A were prepared using similar procedure described in the synthesis of I-1 & I-2 with appropriate variations in cyclization methods, reactants, quantities of reagents and solvents, and reaction conditions. The characterization data of the compounds are summarized herein the below table. Table-A: Int. Starting Intermediate Spectral data No. material structure A-1 LC-MS: 241.9 [M-H]- A-2 LC-MS: 245.9 [M-H]- A-3 LC-MS: 262.0 [M-H]- A-4 LC-MS: 277.9 [M-H]- A-5 LC-MS: 241.9 [M-H]- Synthesis of 7-bromobenzo[d]thiazole-2-thiol (I-3): To the stirred solution of 3-bromo-2-fluoroaniline (2 g, 10.52 mmol) in DMF (20 mL) was added potassium ethyl xanthate (3.73 g, 23.1 mmol) at RT. The resulting reaction mixture was stirred at 120⁰C for 3h. After the completion of reaction, the reaction mixture was cooled to RT and acidified with 1N HCl. The precipitated solid was filtered, washed with water, and dried to get the intermediate- I-3 (1.9 g). This was used as such in the next step without any further purification. LC-MS: 248.0 [M+H+2]⁺. The intermediates listed below in Table-B were prepared using a similar procedure described in the synthesis of intermediate-I-3 with appropriate variations in cyclization methods, reactants, quantities of reagents and solvents, and reaction conditions. The characterization data of the compounds are summarized herein the below table. Table-B: Int. Intermediate Starting material Spectral data No. structure B-1 LC-MS: 263.9 [M-H]- B-2 LC-MS: 277.7 [M-H]- B-3 LC-MS: 184.9 [M-H]- Synthesis of (R)-2-(3-(azetidin-3-yl)piperidin-1-yl)ethan-1-ol (I-4) Step-1: Synthesis of tert-butyl (R)-3-(1-(2-hydroxyethyl)piperidin-3-yl)azetidine-1- carboxylate To a stirred solution of tert-butyl (R)-3-(piperidin-3-yl)azetidine-1-carboxylate (2 g, 8.32 mmol) in acetonitrile (50 mL) was added K₂CO₃ (3.45g, 24.96 mmol) and 2-iodoethan-1-ol (2.86 g, 16.64 mmol) at 0 °C. The reaction mixture was stirred at 80 °C for 16h. Then the reaction mixture was cooled to RT, quenched with ice water and extracted with ethyl acetate. The organic portion was dried and concentrated to get the intermediate- 4a (2.6 g). LC-MS: 285.3 [M+H]⁺ . Step-2: Synthesis of (R)-2-(3-(azetidin-3-yl)piperidin-1-yl)ethan-1-ol To a stirred solution of tert-butyl (R)-3-(1-(2-hydroxyethyl)piperidin-3-yl)azetidine-1- carboxylate (2.5g, 8.78 mmol) in DCM (10mL) was added 4M HCl in dioxane at 0 °C. The reaction mixture was stirred for 16h at RT. After completion of the reaction, reaction mixture concentrated to get the intermediate- I-4. LC-MS: 185.05 [M+H]⁺ . Synthesis of (R)-3-(azetidin-3-yl)-1-(tetrahydro-2H-pyran-4-yl)piperidine (I-5)

Step-1: Synthesis of tert-butyl (R)-3-(1-(tetrahydro-2H-pyran-4-yl)piperidin-3- yl)azetidine-1-carboxylate To a stirred solution of tert-butyl (R)-3-(piperidin-3-yl)azetidine-1-carboxylate (0.1 g, 0.416 mmol), tetrahydro-4H-pyran-4-one (0.062 g, 0.624 mmol) in 1,2-DCE (3 mL) was added sodium triacetoxyborohydride (0.176, 0.83 mmol) in portions. The resultant mixture was stirred at RT for 16h. Then the reaction mixture was quenched with water, extracted with 10% MeOH in DCM, organic portion was dried over Na2SO4 and concentrated to get the intermediate- 5a (0.1 g). LC-MS: 325.2 [M+H]⁺ Step-2: Synthesis of (R)-3-(azetidin-3-yl)-1-(tetrahydro-2H-pyran-4-yl)piperidine To a stirred solution of (R)-3-(1-(tetrahydro-2H-pyran-4-yl)piperidin-3-yl)azetidine-1- carboxylate (0.2g, 0.616 mmol) in DCM (2 mL) was added 4M HCl in dioxane (2mL) at 0 °C. The mixture was stirred at RT for 16h and concentrated to get title intermediate- I-5. LC-MS: 225.0 [M+H]⁺ Synthesis of (R)-4-(3-(azetidin-3-yl)piperidin-1-yl)tetrahydro-2H-thiopyran 1,1-dioxide (I-6)

The intermediate I-6 was prepared using similar procedure described in the synthesis of intermediate I-5 with appropriate variations in coupling method, reactants, quantities of reagents and solvents, and reaction conditions. LC-MS: 273.0 [M+H]⁺ Synthesis of (R)-N-(2-(3-(azetidin-3-yl)piperidin-1-yl)ethyl)acetamide (I-7)

Step-1: Synthesis of tert-butyl (R)-3-(1-(2-(1,3-dioxoisoindolin-2-yl)ethyl)piperidin-3- yl)azetidine-1-carboxylate This intermediate was prepared using a similar procedure described in Step-1 of I-5 with appropriate variations in coupling method, reactants, quantities of reagents and solvents, and reaction conditions. LC-MS: 414.3 [M+H]⁺ Step-2: Synthesis of tert-butyl (R)-3-(1-(2-aminoethyl)piperidin-3-yl)azetidine-1- carboxylate To a stirred solution of tert-butyl (R)-3-(1-(2-(1,3-dioxoisoindolin-2-yl)ethyl)piperidin-3- yl)azetidine-1-carboxylate (0.1 g, 0.242 mmol) in ethanol (2.5 mL) was added hydrazine hydrate (0.061 g, 1.21 mmol) and the mixture was heated to 80 °C for 8h. Then the reaction mixture was cooled to RT, added diethyl ether, precipitate formed was filtered, washed with ether and the filtrate was concentrated to get the intermediate-7b (0.08 g). LC-MS: 284.3 [M+H]⁺ Step-3: Synthesis of tert-butyl (R)-3-(1-(2-acetamidoethyl)piperidin-3-yl)azetidine-1- carboxylate To a stirred solution of tert-butyl (R)-3-(1-(2-aminoethyl)piperidin-3-yl)azetidine-1- carboxylate (0.08 g, 0.282 mmol), triethylamine (0.086 g, 0.85 mmol) in DCM (1 mL) was added acetic anhydride (0.029 g, 0.28 mmol) dropwise at 0 °C. Reaction mixture was gradually warmed to RT and stirred for 2h and after completion, reaction mixture was quenched with water. Organic layer extracted with DCM, washed with Na₂SO₄ and concentrated to get intermediate-7c (0.05 g). LC-MS: 326.2 [M+H]⁺ Step-4: Synthesis of (R)-N-(2-(3-(azetidin-3-yl)piperidin-1-yl)ethyl)acetamide This intermediate I-7 was prepared using a similar procedure described in Step-2 of intermediate- I-5 with appropriate variations in coupling method, reactants, quantities of reagents and solvents, and reaction conditions. LC-MS: 226.2 [M+H]⁺. Synthesis of (R)-N-(2-(3-(azetidin-3-yl)piperidin-1-yl)ethyl)methanesulfonamide (I-8)

The intermediate I-8 was prepared using similar procedure described in the synthesis of intermediate-I-7 with appropriate variations in coupling method, reactants, quantities of reagents and solvents, and reaction conditions. LC-MS: 262.1 [M+H]⁺ Synthesis of 7-bromo-6-fluoro-2-(methylthio)benzo[d]thiazole (I-9): Step-1: Synthesis of 7-bromo-6-fluoro-2-(methylthio)benzo[d]thiazole To a stirred solution of intermediate-B-1 (1 g, 3.78 mmol) in DMF (15 mL) was added K2CO3 (1.045 g, 7.45 mmol) and stirred at RT for ten minutes. The mixture was added MeI (1.075 g, 7.57 mmol) dropwise and stirred at RT for 5h. Then the reaction mixture was diluted with water and extracted with ethyl acetate. Then organic portion was washed with water, dried over Na2SO4 and concentrated. The crude compound was purified by Combiflash chromatography using 14% ethyl acetate in hexane to afford pure intermediate-I-9 (0.8 g, 75.9%). LC-MS: 275.9 [M-H]- The intermediates listed below in Table-C were prepared using a similar procedure described in the synthesis of intermediate-I-9 with appropriate variations in cyclization methods, reactants, quantities of reagents and solvents, and reaction conditions. The characterization data of the compounds are summarized herein the below table. Table-C: Intermediate Int. No. Starting material Spectral data structure C^-1 _B-3 LC-MS: 199.0 [M-H]- C-2 B-2 LC-MS: 292.8 [M-H]- Synthesis of (R)-1-(3-(azetidin-3-yl)piperidin-1-yl)-2-methylpropan-2-ol (I-10):

Step-1: Synthesis of tert-butyl (R)-3-(1-(2-hydroxy-2-methylpropyl)piperidin-3- yl)azetidine-1-carboxylate To a stirred solution of tert-butyl (R)-3-(piperidin-3-yl)azetidine-1-carboxylate (0.1 g, 0.42 mmol) in DMF (2 mL) was added Cs2CO3 (0.27 g, 0.83 mmol) and 2,2-dimethyloxirane (0.15 g, 2.08 mmol) at 0 °C. The reaction mixture was stirred at 100 °C for 24h. Then the reaction mixture was cooled to RT, quenched with ice water and extracted with ethyl acetate. The organic portion was dried and concentrated to get the crude compound. The crude compound was purified by flash chromatography using 5-10% methanol in dichloromethane as eluent to afford the pure intermediate-10a (0.1 g, 77%). LC-MS: 313.05 [M+H]⁺. Step-2: Synthesis of (R)-1-(3-(azetidin-3-yl)piperidin-1-yl)-2-methylpropan-2-ol To a stirred solution of R)-3-(1-(2-hydroxy-2-methylpropyl)piperidin-3-yl)azetidine-1- carboxylate (0.1g, 0.32 mmol) in DCM (5 mL) was added 4M HCl in dioxane (1 mL) at 0 °C. The reaction mixture was stirred for 16h at RT. After completion of the reaction, reaction mixture was concentrated. Obtained residue was diluted further with DCM and washed with saturated aqueous NaHCO₃ solution. The organic portion was dried and concentrated to get the crude intermediate-I-10 (0.1 g). LC-MS: 213.1 [M+H]⁺ . Synthesis of (R)-1-((3-(azetidin-3-yl)piperidin-1-yl)methyl)cyclopropan-1-ol hydrochloride (I-11):

Step-1: Synthesis of methyl 1-((tetrahydro-2H-pyran-2-yl)oxy)cyclopropane-1- carboxylate To a stirred solution of methyl 1-hydroxycyclopropane-1-carboxylate (2.0 g, 17.22 mmol) in DCM (20 mL) was added PPTS (0.43 g, 1.72 mmol) and 3,4-dihydro-2H-pyran (1.74 g, 20.7 mmol) at 0 °C. The reaction mixture was stirred at RT for 12h. Then the reaction mixture was cooled to RT and evaporated to dryness to get the crude compound. The crude compound was purified by flash chromatography using 100% hexane as eluent to afford the pure intermediate- 11b (3 g, 87%). LC-MS: 201.1 [M+H]⁺. Step-2: Synthesis of (1-((tetrahydro-2H-pyran-2-yl)oxy)cyclopropyl)methanol To a stirred solution of methyl 1-((tetrahydro-2H-pyran-2-yl)oxy)cyclopropane-1-carboxylate (3g, 14.98 mmol) in THF (30 mL) was added 2M Lithium aluminum hydride in THF (1.14 g, 29.96 mmol) at 0 °C. The reaction mixture was stirred for 2h at RT. After completion of the reaction, reaction mixture was quenched with saturated aqueous NH4Cl solution and extracted with EtOAc. The organic phase was dried and concentrated to get the crude compound. The crude compound was purified by flash chromatography using 5% ethyl acetate in hexane as eluent to afford the pure intermediate-11c (2.5 g, 97%). Step-3: Synthesis of 1-((tetrahydro-2H-pyran-2-yl)oxy)cyclopropane-1-carbaldehyde To a stirred solution of (1-((tetrahydro-2H-pyran-2-yl)oxy)cyclopropyl)methanol (1g, 5.81 mmol) in DCM (25 mL) was added Dess-martin’s periodinane (3.7 g, 8.71 mmol) at 0 °C. The reaction mixture was stirred for 3h at RT. After completion of the reaction, the reaction mixture was quenched with saturated aqueous NaHCO₃ solution and extracted with DCM. The organic phase was dried and concentrated to get the crude compound. The crude compound was purified by flash chromatography using 10% ethyl acetate in hexane as eluent to afford the pure intermediate-11d (0.75 g, 75%). Step-4: Synthesis of tert-butyl 3-((3R)-1-((1-((tetrahydro-2H-pyran-2- yl)oxy)cyclopropyl)methyl)piperidin-3-yl)azetidine-1-carboxylate To a stirred solution of 1-((tetrahydro-2H-pyran-2-yl)oxy)cyclopropane-1-carbaldehyde (0.48g, 2.82 mmol), tert-butyl (R)-3-(piperidin-3-yl)azetidine-1-carboxylate (0.61 g, 2.54 mmol) in 1,2-DCE (4 mL) was stirred for 12h at RT. After 12h, was added STAB (1.2 g, 5.63 mmol) at 0 °C. The reaction mixture was stirred for 3h at RT. After completion of the reaction, the reaction mixture was quenched with ice water and extracted with DCM. The organic phase was dried and concentrated to get the crude compound. The crude compound was purified by flash chromatography using 10% MeOH in DCM as eluent to afford the pure intermediate-11e (0.6 g, 54%). Step-5: Synthesis of (R)-1-((3-(azetidin-3-yl)piperidin-1-yl)methyl)cyclopropan-1-ol hydrochloride To a stirred solution of tert-butyl 3-((3R)-1-((1-((tetrahydro-2H-pyran-2- yl)oxy)cyclopropyl)methyl)piperidin-3-yl)azetidine-1-carboxylate (0.5 g, 1.27 mmol) in DCM (5 mL) was added 4M HCl in dioxane (5 mL) at 0 °C. The reaction mixture was stirred for 12h at RT. After completion of the reaction, reaction mixture concentrated to get the crude intermediate-I-11 (0.6 g). LC-MS: 211.05 [M+H]⁺ . Synthesis of 7-chloro-2-(methylthio)thiazolo[4,5-d]pyrimidine (I-12)

Step-1: Synthesis of 4-amino-2-(methylthio)thiazole-5-carbonitrile To a stirred suspension of Na₂S (5.4 g, 68.4 mmol, 1 eq.) in DMF (80 mL), dimethyl cyanodithioiminocarbonate (10 g, 68.4 mmol, 1 eq.) was added and heated the reaction mixture at 70 °C for 2 hours. Chloroacetonitrile (10.3 g, 136.8 mmol, 2 eq.) was then added slowly at 70 °C to the reaction mixture and stir for 2 hrs at the same temperature followed by potassium carbonate was added to the reaction mixture and stirred for 1 h at the same temperature. After the completion of reaction pour the mixture onto water under good stirring to get solid precipitate, which was filtered and washed with water, dried under vacuum to get intermediate- 12c (7.8 g crude yield). LC-MS: 172.2 [M+H]⁺ . Step-2 Synthesis of 2-(methylthio)thiazolo[4,5-d]pyrimidin-7(6H)-one (12d) To a stirred solution of intermediate-12c (1.1 g, 6.42 mmol) in formic acid (4 mL), water (1drop) was added and heated to reflux for 4 hrs. The progress of the reaction was monitored by TLC. The mixture was allowed to stand at RT and after completion of the reaction was added to ice water to get precipitate, which was collected by filtration, washed with water, dried under vacuum to get intermediate-12d (0.85 g crude yield). LC-MS: 200.2 [M+H]⁺ . Step-3: Synthesis of 7-chloro-2-(methylthio)thiazolo[4,5-d]pyrimidine (I-12) To a stirred solution of 12d (0.1 g, 0.5 mmol) in POCl3 (1 mL) was heated at 110 ^oC for 1 hr. The progress of the reaction was monitored by TLC analysis. After completion of the reaction added to the ice water to get precipitate, which was collected by filtration, washed with water, dried under vacuum to get intermediate-I-12 (0.05 g crude yield). LC-MS: 218.7 [M+H]⁺ . Synthesis of 6-fluoro-7-iodo-2-(methylthio)thiazolo[4,5-b]pyridine (I-13): Step-1: Synthesis of 6-fluoro-7-iodo-2-(methylthio)thiazolo[4,5-b]pyridine To the stirred solution of 6-fluoro-2-(methylthio)thiazolo[4,5-b]pyridine (0.75 g, 3.74 mmol) in dry THF (10 mL), was cooled to -78 ^oC and added 2M LDA solution in THF (1.20 g, 11.23 mmol) at -78 ^oC and stirred for 1h at the same temperature. After 1h, was added molecular iodine (1.9 g, 7.49 mmol) in dry THF (5 mL) at -78 °C in 10 min and the reaction mixture was gradually warmed to RT and stirred for 14h. After the completion of reaction, the reaction mixture was cooled to 0 °C and quenched with aqueous sodium thiosulphate solution. Extracted with excess of ethyl acetate, washed with water, brine, dried over anhydrous Na₂SO₄ and concentrated under vacuum to afford the intermediate-I-13 (1 g). LC-MS: 326.9 [M+H]⁺. Synthesis of 2-(2-(azetidin-3-yl)morpholino)ethan-1-ol (I-14):

Step-1: Synthesis of tert-butyl 3-formylazetidine-1-carboxylate To the stirred solution of tert-butyl 3-(hydroxymethyl) azetidine-1-carboxylate (5 g, 26.70 mmol) in DCM (50 mL) was added Dess martin periodinane (13.59 g, 32.04 mmol) at 0 °C. The resulting reaction mixture was stirred at RT for 2h. The reaction was monitored by TLC and showed that absence of starting material. The reaction mixture was cooled to 0 °C and reaction mixture was poured in saturated NaHCO₃ solution and extracted with DCM, organic layer was washed with brine and dried over on anhydrous Na2SO4 and concentrated under reduced pressure to afford the crude material. The crude material was purified by flash chromatography and eluted with 0-60% EtOAc in hexane to afford the intermediate-14b (4.5 g, 91%).¹H NMR (400 MHz, CDCl3) δ 9.86 (s, 1H), 4.164-4.081 (m, 4H), 1.460 (S, 9H) Step-2: Synthesis of tert-butyl 3-(1-hydroxy-2-nitroethyl) azetidine-1-carboxylate To the stirred solution of tert-butyl 3-formylazetidine-1-carboxylate (4.5 g, 24.25 mmol) in MeOH (50 mL) was added Triethylamine (7.3 g, 72.80 mmol) and Nitromethane (4.45 g, 72.88 mmol) at 0 °C. The resulting reaction mixture was stirred RT for 16h. The reaction was monitored by TLC and showed that absence of starting material. The reaction mixture was concentrated under reduced pressure to afford the crude material. Crude material was purified by flash chromatography and eluted with 0-60% EtOAc in hexane to afford the intermediate- 14c (4.40 g, 91%). LC-MS: 247.1 [M+H]⁺ Step-3: Synthesis of tert-butyl 3-(2-amino-1-hydroxyethyl) azetidine-1-carboxylate To the stirred solution of tert-butyl 3-(1-hydroxy-2-nitroethyl) azetidine-1-carboxylate (4 g, 16.24 mmol) in MeOH (50 mL) was added Pd/C (10%) (1.3 g) at RT. The resulting reaction mixture was stirred at RT under H2 balloon pressure (30 psi) for 16 h. The reaction was monitored by TLC and showed that absence of starting material and reaction mixture was filtered through celite pad and washed further with excess of MeOH. Filtrate was concentrated under reduced pressure to afford the crude intermediate-14d (4.0 g). LC-MS: 217.2 [M+H] ⁺ Step-4: Synthesis of tert-butyl 3-(2-(2-chloroacetamido)-1-hydroxyethyl) azetidine-1- carboxylate To the stirred solution of tert-butyl 3-(2-amino-1-hydroxyethyl) azetidine-1-carboxylate (3.7 g, 17.11 mmol) in DCM (40 mL) was added Triethylamine (5.19 g, 51.32 mmol) and Chloro acetyl chloride (2.13 g, 18.81 mmol) at 0 °C. The resulting reaction mixture was stirred at RT for 16h. The reaction was monitored by TLC and showed that absence of starting material. The reaction mixture was cooled to 0 °C and reaction mixture was poured in saturated NaHCO₃ solution and extracted with DCM, organic layer was washed with brine and dried over on anhydrous Na₂SO₄ and concentrated under reduced pressure to afford the crude compound. The crude compound was purified by flash chromatography and eluted with 0-80% EtOAc in hexane to afford the intermediate-14e (2.8 g 56%). LC-MS: 193.1[M-Boc] ⁺ Step-5: Synthesis of tert-butyl 3-(5-oxomorpholin-2-yl) azetidine-1-carboxylate To the stirred solution of tert-butyl 3-(2-(2-chloroacetamido)-1-hydroxyethyl) azetidine-1- carboxylate (2.7 g, 9.22 mmol) in tBuOH (25 mL) was added KOtBu (2.07 g, 18.44 mmol) at 0 °C. The resulting reaction mixture was stirred at RT for 3h. The reaction was monitored by TLC and showed that absence of starting material. The reaction mixture was cooled to 0 °C and reaction mixture was poured in ice water and extracted with EtOAc, organic layer was washed with brine and dried over on anhydrous Na₂SO₄ and concentrated under reduced pressure to afford the crude intermediate-14f (2.2 g). LC-MS: 157.1[M-Boc] ⁺ Step-6: Synthesis of tert-butyl 3-(morpholin-2-yl) azetidine-1-carboxylate To the stirred solution of tert-butyl 3-(5-oxomorpholin-2-yl) azetidine-1-carboxylate (0.9 g, 3.51 mmol) in THF (15 mL) was added BH₃ in THF (1M) (0.91g, 10.53 mmol) dropwise at 0 ^oC. The resulting reaction mixture was stirred at RT for 6h. The reaction was monitored by TLC and showed that absence of starting material. The reaction mixture was cooled to 0 °C and reaction mixture was quenched with MeOH slowly and concentrated under reduced pressure to afford the crude material. Crude material was purified by flash chromatography and eluted with 0-20% MeOH in DCM to afford the intermediate-14g (0.35 g, 41%). LC-MS: 243.2 [M+1] ⁺ Step-7: Synthesis of tert-butyl (R)-3-(1-(2-hydroxyethyl)piperidin-3-yl)azetidine-1- carboxylate To a stirred solution of tert-butyl 3-(morpholin-2-yl)azetidine-1-carboxylate (2 g, 8.26 mmol) in acetonitrile (50 mL) was added K₂CO₃ (3.45 g, 24.8 mmol) and 2-iodoethan-1-ol (2.86 g, 16.64 mmol) at 0 °C. The reaction mixture was stirred at 80 °C for 16h. Then the reaction mixture was cooled to RT, quenched with ice water, and extracted with ethyl acetate. The organic portion was dried and concentrated to get the intermediate-14h (2.6 g). LC-MS: 287.4 [M+H]⁺ . Step-8: Synthesis of 2-(2-(azetidin-3-yl)morpholino)ethan-1-ol To a stirred solution of tert-butyl tert-butyl 3-(4-(2-hydroxyethyl)morpholin-2-yl)azetidine-1- carboxylate (2.5 g, 8.78 mmol) in DCM (10 mL) was added 4M HCl in dioxane at 0 °C. The reaction mixture was stirred for 16 h at RT. After completion of the reaction, reaction mixture concentrated to get the intermediate- I-14. LC-MS: 187.05 [M+H]⁺ . Synthesis of 2-((R)-3-(azetidin-3-yl)piperidin-1-yl)propan-1-ol (I-15) Step-1: Synthesis of tert-butyl 3-((3R)-1-(1-hydroxypropan-2-yl)piperidin-3-yl)azetidine- 1-carboxylate To a stirred solution of tert-butyl (R)-3-(piperidin-3-yl)azetidine-1-carboxylate (1 g, 4.16 mmol, 1 eq.), 1-hydroxypropan-2-one (6.16 g, 83.2 mmol, 20 eq.), in MeOH (10 mL) and CH2Cl2 (10 mL) was added acetic acid (cat.) and stirred for 10 min at RT. The reaction mixture was cooled to 0 ^oC and NaCNBH₃ was added portion wise and stirred at 35 ^oC for 16h. After the completion of reaction quenched with NaHCO₃ solution and extracted with CH₂Cl₂ (2 times), concentrated to get the intermediate-15a. LC-MS: 299.4 [M+H]⁺ . Step-2: Synthesis of 2-((R)-3-(azetidin-3-yl)piperidin-1-yl)propan-1-ol To a stirred solution of tert-butyl 3-((3R)-1-(1-hydroxypropan-2-yl)piperidin-3-yl)azetidine-1- carboxylate (2.5 g, 8.4 mmol) in DCM (10 mL) was added 4M HCl in dioxane at 0 °C. The reaction mixture was stirred for 2 h at RT. After completion of the reaction, reaction mixture concentrated to get the intermediate-I-15. LC-MS: 199.3 [M+H]⁺ . Synthesis of (R)-(3-(azetidin-3-yl)piperidin-1-yl)(1-hydroxycyclopropyl)methanone (I-16)

Step-1: Synthesis of tert-butyl (R)-3-(1-(1-hydroxycyclopropane-1-carbonyl)piperidin-3- yl)azetidine-1-carboxylate To a stirred solution of 1-hydroxycyclopropane-1-carboxylic acid (0.64 g, 6.24 mmol, 1.5 eq.) in CH₂Cl₂ (13 mL), EDCI (1.2 g, 6.24 mmol, 1.5 eq.), HOBt (0.7 g, 4.57 mmol, 1.1 eq), 4- methyl morpholine (0.9 g, 9.15 mmol, 2.2 eq.) were added and continued for 15 min. tert-Butyl (R)-3-(piperidin-3-yl)azetidine-1-carboxylate (1 g, 4.16 mmol, 1 eq.) in CH2Cl2 (5 mL) was added to the reaction mixture slowly dropwise and kept for overnight at RT. After the completion of reaction quenched with NaHCO3 solution and extracted with CH2Cl2 (2 times), washed with brine, dried over Na2SO4, concentrated to get the intermediate-16b. LC-MS: 325.4 [M+H]⁺ . Step-2: Synthesis of (R)-(3-(azetidin-3-yl)piperidin-1-yl)(1- hydroxycyclopropyl)methanone To a stirred solution of tert-butyl (R)-3-(1-(1-hydroxycyclopropane-1-carbonyl)piperidin-3- yl)azetidine-1-carboxylate (1 g, 3.1 mmol) in DCM (10 mL) was added 4M HCl in dioxane at 0 °C. The reaction mixture was stirred for 12 h at RT. After completion of the reaction, reaction mixture concentrated to get the intermediate- I-16. LC-MS: 225.3 [M+H]⁺ . Synthesis of 2-(5-(azetidin-3-yl)-2-methylpiperidin-1-yl)ethan-1-ol (I-17):

Step-1: Synthesis of tert-butyl 3-(6-methylpyridin-3-yl)azetidine-1-carboxylate To a stirred solution of zinc (7.6 g, 116.3 mmol, 10 eq.) in anhydrous DMF (40 mL) was added 12-dibromoethane (0.22 g, 1.16 mmol, 0.1 eq.) and the mixture was heated to 75 ^oC for 15 min and cooled to RT. Trimethylsilyl chloride (0.13 g, 1.16 mmol, 0.1 eq.) was then added and stirred at RT for 30 min. A solution of tert-butyl 3-iodoazetidine-1-carboxylate (13.2 g, 46.5 mmol, 4 eq.) in DMF (10 mL) was added and the mixture stirred at RT for 30 min followed by addition of 5-bromo-2-methylpyridine (2 g, 11.6 mmol, 1 eq.) and RuPhos Pd G4 in DMF (10 mL). The reaction mixture was stirred at 80 °C for 2h and progress of the reaction was monitored by TLC. After the completion of reaction, cooled to RT and quenched with saturated NH4Cl solution, filtered through celite pad, and washed with ethyl acetate (2 times). The filtrate was washed with cold water and the organic layer was dried over Na₂SO₄, concentrated to afford crude compound which was purified by flash column chromatography eluting with 90% ethyl acetate in hexane to afford pure intermediate-17b. LC-MS: 249.3 [M+H]⁺ . Step-2: Synthesis of tert-butyl 3-(6-methylpiperidin-3-yl)azetidine-1-carboxylate To a stirred solution of tert-butyl 3-(6-methylpyridin-3-yl)azetidine-1-carboxylate (1.8 g, 7.25 mmol, 1 eq.) in EtOH (50 mL) was added concentrated sulfuric acid (0.36 g, 0.5 eq.) followed by Platinum dioxide (0.41 g, 1.81 mmol, 0.25 mmol) at RT. Reaction mixture stirred under hydrogen pressure for 2h. Reaction progress was monitored by TLC. After the completion of reaction mixture was filtered through celite and washed by 20% Methanol/DCM. The organic layer was dried under reduced pressure to afford crude intermediate-17c which was used for next reaction. LC-MS: 255.4 [M+H]⁺ Step-3: Synthesis of tert-butyl 3-(1-(2-hydroxyethyl)-6-methylpiperidin-3-yl)azetidine-1- carboxylate To a stirred solution of tert-butyl 3-(6-methylpiperidin-3-yl)azetidine-1-carboxylate (1.7 g, 6.68 mmol, 1 eq.) in ACN (20 mL) was added potassium carbonate (2.77 g, 20 mmol, 3 eq.) and 2- iodoethan-1-ol (1.72 g, 10 mmol, 3 eq.) at RT. Reaction mixture was stirred at 80 °C for 16h and progress was monitored by TLC. After the completion of reaction quenched by water and extracted with 20% MeOH/DCM (2 times). The organic layer was dried over Na₂SO₄, concentrated under reduced pressure to afford crude compound which was purified by flash chromatography eluting with 12 ~15% MeOH/DCM to afford pure intermediate-17d. LC-MS: 299.4 [M+H]⁺ . Step-4: Synthesis of 2-(5-(azetidin-3-yl)-2-methylpiperidin-1-yl)ethan-1-ol To a stirred solution of tert-butyl 3-(1-(2-hydroxyethyl)-6-methylpiperidin-3-yl)azetidine-1- carboxylate (1 g, 3.35 mmol, 1 eq.) in DCM (15 mL) was added 4M HCl in 14-dioxane (8 mL) at 0 °C. Reaction mixture was stirred at RT for 2h. Reaction progress was monitored by TLC. After the completion of reaction, concentrated under reduced pressure to afford intermediate- I-17. LC-MS: 199.4 [M+H]⁺ . Synthesis of ethyl 2-(3-(azetidin-3-yl)-2,6-dimethylpiperidin-1-yl)-2-oxoacetate (I-18)

Step-1: Synthesis of tert-butyl 3-(2,6-dimethylpyridin-3-yl)azetidine-1-carboxylate To a stirred solution of zinc (7.0 g, 65.4 mmol, 10 eq.) in anhydrous DMF (40 mL) was added 12-dibromoethane (0.2 g, 1.1 mmol, 0.1 eq.) and the mixture was heated to 75 °C. After 15 min the reaction mixture was cooled to RT and trimethylsilyl chloride (0.12 g, 1.1 mmol, 0.1 eq.) was added, stirred at RT for 30 min. To the reaction mixture tert-butyl 3-iodoazetidine-1- carboxylatein (12.2 g, 43 mmol, 4 eq.) in DMF (10 mL) was added and the mixture was stirred at RT for 30 min followed by addition of 3-bromo-2,6-dimethylpyridine (2.0 g, 10.7 mmol, 1 eq.) and RuPhos Pd G4 (0.91 g, 1.1 mmol, 0.1 eq.) in DMF (10 mL). The reaction mixture was stirred at 80 °C for 2h and progress was monitored by TLC. After the completion of reaction, cooled to RT and quenched with saturated NH4Cl solution. The crude mixture was filtered through celite pad and washed with ethyl acetate (2 times). The filtrate was washed with cold water. The organic layer was dried over Na2SO4, concentrated to get the intermediate- 18b. LC- MS: 263.3 [M+H]⁺ . Step-2: Synthesis of tert-butyl 3-(2,6-dimethylpiperidin-3-yl)azetidine-1-carboxylate To a stirred solution of tert-butyl 3-(2,6-dimethylpyridin-3-yl)azetidine-1-carboxylate (1 g, 3.81 mmol, 1 eq.) in EtOH (20 mL) was added concentrated sulfuric acid (0.18 g, 1.9 mmol, 0.5 eq.) followed by platinum oxide (0.2 g, 0.95 mmol, 0.2 eq.) at RT. Reaction mixture was stirred under hydrogen pressure for 16h and reaction progress was monitored by TLC. After the completion of reaction, filtered through celite and washed by 20% Methanol/DCM. The organic layer dried under reduced pressure to afford pure intermediate-18c. LC-MS: 269.4 [M+H]⁺ . Step-3: Synthesis of tert-butyl 3-(1-(2-ethoxy-2-oxoacetyl)-2,6-dimethylpiperidin-3- yl)azetidine-1-carboxylate To a stirred solution of tert-butyl 3-(2,6-dimethylpiperidin-3-yl)azetidine-1-carboxylate (0.8 g, 2.98 mmol, 1 eq.) in DMF (15 mL) was added 60% sodium hydride (0.13 g, 5.8 mmol, 1.3 eq.) at 40 °C and stirred for 1h at that temperature. The reaction mixture cooled to RT and ethyl 2- chloro-2-oxoacetate (0.73 g, 5.36 mmol, 1.2 eq.) was added and stirred at RT for 16h. Reaction progress was monitored by TLC and after the completion of reaction quenched with water, extracted with DCM (2 times), concentrated under reduced pressure to afford crude compound which was purified by normal phase chromatography using (10-12%) MeOH/DCM eluent to afford pure intermediate-18e. LC-MS: 369.4 [M+H]⁺ . Step-4: Synthesis of ethyl 2-(3-(azetidin-3-yl)-2,6-dimethylpiperidin-1-yl)-2-oxoacetate To a stirred solution of tert-butyl 3-(1-(2-ethoxy-2-oxoacetyl)-2,6-dimethylpiperidin-3- yl)azetidine-1-carboxylate (600 mg, 1.63 mmol) in DCM (10 mL) was added 4M HCl in Dioxane (2 mL) at 0 °C and stirred at RT for 2h. Reaction progress was monitored by TLC and after the completion of reaction, concentrated under reduced pressure to afford intermediate I- 18. LC-MS: 269.3 [M+H]⁺ . Synthesis of 2-(4-(azetidin-3-yl)piperidin-1-yl)ethan-1-ol (I-19):

Step-1: Synthesis of tert-butyl 3-hydroxy-3-(pyridin-4-yl)azetidine-1-carboxylate To a stirred solution of 4-iodopyridine (1 g, 4.88 mmol, 1 eq.) in THF (20 mL) was added 1.6 M n-BuLi (4.6 mL, 7.32 mmol) at −78 °C and the reaction mixture was stirred for 30 min. tert- Butyl 3-oxoazetidine-1- carboxylate (1.67 g, 9.75 mmol, 2 eq.) in THF (10 mL) was added to the reaction mixture at -78 °C and allow to stir for 3h at the same temperature. Reaction mixture was monitored by TLC. After the completion of reaction, quenched with saturated NH4Cl solution and extracted with ethyl acetate (2 times). The organic layer was dried over sodium sulfate, concentrated under reduced pressure to afford crude compound which was purified by flash chromatography using 5% DCM/MeOH as eluent to afford pure intermediate-19c. LC- MS: 251.3 [M+H]⁺ . Step-2: Synthesis of tert-butyl 3-((methylsulfonyl)oxy)-3-(pyridin-4-yl)azetidine-1- carboxylate To a stirred solution of tert-butyl 3-hydroxy-3-(pyridin-4-yl)azetidine-1-carboxylate (0.43 g, 1.72 mmol, 1 eq.) in DCM (10 mL) was added Et₃N (2.1 mL, 5.16 mmol, 3 eq.) and MsCl (0.19 mL, 2.57 mmol, 1.5 eq.) at 0 °C and stirred at RT for 1 h. Progress of the reaction was moniterd by TLC. After the completion of reaction, quenched with saturated NaHCO3 solution and extracted with DCM (2 times). The combined organic layer was dried over Na₂SO₄ and concentrated under reduced pressure to get crude product which was purified by flash chromatography using 5% DCM/MeOH as eluent to afford pure intermediate- 19d. LC-MS: 329.4 [M+H]⁺ . Step-3: Synthesis of tert-butyl 3-(piperidin-4-yl)azetidine-1-carboxylate To a stirred solution of tert-butyl 3-((methylsulfonyl)oxy)-3-(pyridin-4-yl)azetidine-1- carboxylate (0.5 g, 1.52 mmol, 1 eq.) in EtOH (15 mL) was added conc. sulfuric acid (0.1 g, 1.02 mmol, 0.6 eq.), followed by PtO2 (0.1 g, 0.45 mmol, 0.3 eq.) was added and stirred the reaction mixture under hydrogen pressure for 4h. After the completion of reaction, filtered through celite and filtrate was concentrated under reduced pressure to afford crude compound which was purified by flash chromatography using 15% DCM/MeOH as eluent to afford intermediate-19e. LC-MS: 241.3 [M+H]⁺ . Step-4: Synthesis of tert-butyl 3-(1-(2-hydroxyethyl)piperidin-4-yl)azetidine-1- carboxylate To a stirred solution of tert-butyl 3-(piperidin-4-yl)azetidine-1-carboxylate (0.27 g, 1.12 mmol, 1 eq.) in DMF (7 mL) was added K2CO3 (0.47 mmol, 3.36 mmol, 3 eq.) followed by 2- iodoethan-1-ol (0.29 g, 1.68 mmol, 1.5 eq.) at 0 °C and stirred at 80 °C for 4h. Progress of the reaction was moniterd by TLC. After the completion of reaction, quenched with ice water and extracted with EtOAc (2 times). The combined organic layer was dried over Na2SO4 and concentrated under reduced pressure to get crude material which was purified by flash chromatography using 10% DCM/MeOH as eluent to afford pure intermediate-19f. LC-MS: 285.4 [M+H]⁺ . Step-5: Synthesis of 2-(4-(azetidin-3-yl)piperidin-1-yl)ethan-1-ol To a stirred solution of tert-butyl 3-(1-(2-hydroxyethyl)piperidin-4-yl)azetidine-1-carboxylate (0.15 g, 0.527 mmol, 1 eq.) in DCM (5 mL), 4M HCl in 1,4-dioxane (2 mL) was added at 0°C and stirred the reaction mixture at RT for 16h. After the completion of reaction, concentrated under reduced pressure to afford intermediate-I-19. LC-MS: 185.3 [M+H]⁺ . GENERAL SCHEMES General Scheme-1:

Some of the exemplary compounds of the present application were synthesized as depicted in General Scheme-1. GS-1.1 when reacted with alkyl halide in presence of a base afforded GS- 1.2, which under Buchwald coupling conditions reacted with GS-1.3 to afford GS-1.4. This GS- 1.4 upon oxidation in presence of an oxidizing agent and an appropriate solvent gave GS-1.5, (Note: when X1 = S, GS-1.7 was formed). GS-1.5 upon reaction with GS-1.6 in appropriate solvent and base afforded a compound of formula (I-1). General Scheme – 2:

Some of the exemplary compounds of the present application were synthesized as depicted in General Scheme-2. GS-1.1 when reacted with a chlorinating agent (ex.: sulfuryl chloride) afforded GS-2.2, which under Buchwald coupling conditions reacted with GS-1.6 to afford GS- 2.3. This GS-2.3 upon coupling with GS-1.3 under Buchwald coupling conditions afforded a compound of formula (I-1). EXAMPLES: Example-1: Synthesis of 2-((R)-3-(1-(6-chloro-7-(((R)-1-(2,4- dichlorophenyl)ethyl)amino)benzo[d]oxazol-2-yl)azetidin-3-yl)piperidin-1-yl)ethan-1-ol (Compound-1)

Step-1: Synthesis of 7-bromo-6-chloro-2-(methylthio)benzo[d]oxazole To the stirred solution of intermediate-I-1(2 g, 7.56 mmol) in DMF (20 mL) was added anhydrous K₂CO₃ (2.09 g, 15.12 mmol) at 0 °C and stirred for 10 minutes. Then, iodomethane (1.61 g, 11.34 mmol) was added at same temperature and gradually warmed to RT. The resulting reaction mixture was stirred at RT for 2h. After the completion of reaction, the reaction mixture was poured into cold water, extracted with ethyl acetate and the layers were separated. The organic portion was again washed with water, separated, dried over Na2SO4, filtered and concentrated to get the crude compound. The crude compound was purified by flash chromatography using 0-10% ethyl acetate in hexane as eluent to afford the pure title intermediate-1A (1.5 g, 71.2%). LC-MS: 279.9 [M+H]⁺ Step-2: Synthesis of (R)-6-chloro-N-(1-(2,4-dichlorophenyl)ethyl)-2- (methylthio)benzo[d]oxazol-7-amine In a seal tube, 7-bromo-6-chloro-2-(methylthio)benzo[d]oxazole (0.1 g, 0.35 mmol) and (R)-1- (2,4-dichlorophenyl)ethan-1-amine (0.102 g, 0.538 mmol) in toluene (6 mL) was purged with argon for 5 minutes at RT, then were added Xantphos (0.042 g, 0.07 mmol), Pd2(dba)3 (0.33 g, 0.03 mmol), sodium tertiary butoxide one followed by another and again purged with argon gas for another 5 minutes. The reaction mixture was heated to 100 °C and stirred for 1.5h. After the completion of reaction, the reaction mixture was cooled to RT and concentrated to get crude compound. The crude compound was purified by flash chromatography on silica gel column using 0-10% ethyl acetate in hexane as eluent. This afforded the pure intermediate-1B (0.08 g, 71.8%). LC-MS: 387.0 [M+H]⁺ Step-3: Synthesis of 6-chloro-N-((R)-1-(2,4-dichlorophenyl)ethyl)-2- (methylsulfinyl)benzo[d]oxazol-7-amine To the stirred solution of (R)-6-chloro-N-(1-(2,4-dichlorophenyl)ethyl)-2- (methylthio)benzo[d]oxazol-7-amine (0.07 g, 0.181 mmol) in chloroform (3 mL) was added mCPBA (0.047 g, 0.27 mmol) at 0 °C. The resulting reaction mixture was stirred at RT for 2h. After the completion of reaction, the reaction mixture was quenched with saturated aq. NaHCO₃, extracted with DCM and the layers were separated. The organic portion was washed again with water, dried over Na2SO4, filtered and concentrated to get the intermediate-1C (0.15 g). LC-MS: 404.9 [M+H]⁺ Step-4: Synthesis of 2-((R)-3-(1-(6-chloro-7-(((R)-1-(2,4- dichlorophenyl)ethyl)amino)benzo[d]oxazol-2-yl)azetidin-3-yl)piperidin-1-yl)ethan-1-ol To the stirred solution of 6-chloro-N-((R)-1-(2,4-dichlorophenyl)ethyl)-2- (methylsulfinyl)benzo[d]oxazol-7-amine (0.08 g, 0.198 mmol), (R)-2-(3-(azetidin-3- yl)piperidin-1-yl)ethan-1-ol (0.073 g, 0.396 mmol) in 1:1 ratio of DMF (1 mL) and dioxane (1 mL) at 0 °C and was added DIPEA (0.128 g, 0.99 mmol). The resulted reaction mixture was allowed to reach to RT and stirred at 100 ℃ for 3h. After the completion of reaction, the reaction mixture was cooled to RT, quenched with aq. NH₄Cl, then extracted with ethyl acetate and the layers were separated. The organic portion was dried over Na2SO4, filtered and concentrated to get crude compound. The crude compound was purified by silica gel preparative TLC using 10% methanol in DCM as an eluent. This afforded the pure title compound-1 (0.04 g, 38.5%). LC-MS: 525.1 [M+H]⁺; ¹H-NMR (400 MHz, CD₃OD-d₄): δ 7.46 (d, 1H), 7.38 (d, 1H), 7.28- 7.25 (dd, 1H), 7.10 (d, 1H), 6.59 (d, 1H), 5.51-5.46 (m, 1H), 4.25 (t, 1H), 4.17 (t, 1H), 3.98- 3.94 (m, 1H), 3.81-3.77 (m, 1H), 3.73-3.68 (m, 3H), 3.59-3.57 (m, 1H), 2.98-2.88 (m, 2H), 2.64-2.54 (m, 3H), 2.07-2.05 (m, 1H), 1.87-1.72 (m, 4H), 1.59 (d, 3H). Example-2: Synthesis of 2-((R)-3-(1-(7-(((R)-1-(2,4- dichlorophenyl)ethyl)amino)benzo[d]thiazol-2-yl)azetidin-3-yl)piperidin-1-yl)ethan-1-ol (Compound-2)

Step-1: Synthesis of 7-bromo-2-chlorobenzo[d]thiazole To a stirred solution of intermediate-I-3 (0.9 g, 3.65 mmol) in DCM (10 mL) was added sulfuryl chloride (0.49 g, 134.9 mmol) at 0 °C and then mixture was gradually warmed to RT. After stirring at RT for 12h, the reaction mixture was poured into ice cold Aq. NaHCO₃ solution and extracted with DCM. Then organic portion was washed with brine solution, dried over Na2SO4 and concentrated. The crude compound was purified by Combiflash chromatograph using 15- 20% ethyl acetate in hexane. This afforded pure intermediate-2A (1 g.60.5%). LC-MS: 247.8 [M+H]⁺ Step-2: Synthesis of (R)-2-(3-(1-(7-bromobenzo[d]thiazol-2-yl)azetidin-3-yl)piperidin-1- yl)ethan-1-ol To a stirred solution of 7-bromo-2-chlorobenzo[d]thiazole (0.3 g, 1.2 mmol), (R)-2-(3- (azetidin-3-yl)piperidin-1-yl)ethan-1-ol (0.278 g, 1.5 mmol) in 1:1 DMF-dioxane (5 mL) was added CsF (0.55 g, 3.62 mmol) at RT. The resultant mixture was stirred at 110 °C for 20h. Then the reaction mixture was cooled to RT, diluted with cold water and concentrated. The crude compound was purified by Combiflash chromatography using 5-7% of MeOH in DCM. The yellow solid obtained was triturated with ether and pentane to afford pure intermediate-2B (0.35 g, 37.63%). LC-MS: 397.95 [M+H]⁺ Step-3: Synthesis of 2-((R)-3-(1-(7-(((R)-1-(2,4- dichlorophenyl)ethyl)amino)benzo[d]thiazol-2-yl)azetidin-3-yl)piperidin-1-yl)ethan-1-ol To a stirred solution of (R)-2-(3-(1-(7-bromobenzo[d]thiazol-2-yl)azetidin-3-yl)piperidin-1- yl)ethan-1-ol (0.15 g, 0.378 mmol) in toluene (0.5 mL) was purged with argon and added (R)- 1-(2,4-dichlorophenyl)ethan-1-amine (0.108 g, 0.567 mmol), sodium tert-butoxide (0.109 g, 1.13 mmol), tBu-XPhos (0.064 gm 0.15 mmol), Pd₂dba₃ (0.69 g, 0.07 mmol). The reaction mixture was heated to 100 °C for 20h in a crimped sealed tube. The reaction mixture was then cooled to RT, filtered through celite pad and the filtrate was concentrated. The crude solid was triturated to get yellow solid (0.1 g). This was further purified by preparative HPLC. Method used: Mobile phase-A was 0.05% TFA in water and B was acetonitrile. Gradient program: 20% B at 0 min, 30% B at 2 min, 10% B at 60 min. Column used: Kinetex EVO, C18 (250 ×21.2mm) 5µ with a flow rate of 15 mL/min. This afforded the pure title compound-2 (0.012 g). LC-MS : 505.1 [M+H]⁺ ; ¹H-NMR (400 MHz, CD₃OD-d₄): δ 7.46-7.43 (m, 2H), 7.23-7.21 (dd, 1H), 6.99 (t, 1H), 6.87 (d, 1H), 6.01 (d, 1H), 5.05-5 (m, 1H), 4.28-4,24 (m, 2H), 3.99-3.95 (m, 2H), 3.74(t, 2H), 3.04-3.12 (m, 2H), 2.8-2.6 (m, 2H), 2.25-2.15 (m, 1H), 1.94-1.78 (m, 4H), 1.69-1.6 (m, 1H), 1.55 (d, 3H), 1.02-0.9 (2H). Example-3: Synthesis of 2-((R)-3-(1-(7-(((R)-1-(2,4-dichlorophenyl)ethyl)amino)-6- fluorobenzo[d]thiazol-2-yl)azetidin-3-yl)piperidin-1-yl)ethan-1-ol (Compound-3)

Step- 1: Synthesis of (R)-N-(1-(2,4-dichlorophenyl)ethyl)-6-fluoro-2- (methylthio)benzo[d]thiazol-7-amine A stirred solution of intermediate-I-9 (0.15 g, 0.539 mmol), (R)-1-(2,4-dichlorophenyl)ethan- 1-amine (0.154 g, 0.808 mmol), sodium tert-butoxide (0.155 g, 1.61 mmol) in toluene (5 mL) was purged with argon and added Pd₂dba₃ (0.025 g, 0.02 mmol), rac-BINAP (0.034 g, 0.05 mmol) and stirred at 100 ^oC for 4h. The reaction mixture was then cooled to RT, filtered through celite and concentrated. The crude compound was purified by combiflash chromatography using 8% ethyl acetate in hexane to afford the intermediate- 3B (0.2 g, 95.8%). LC-MS: 387.0 [M+H]⁺ Step- 2: Synthesis of (R)-N-(1-(2,4-dichlorophenyl)ethyl)-6-fluoro-2- (methylsulfonyl)benzo[d]thiazol-7-amine To a stirred solution of (R)-N-(1-(2,4-dichlorophenyl)ethyl)-6-fluoro-2- (methylthio)benzo[d]thiazol-7-amine (0.16 g, 0.413 mmol) in chloroform (3 mL) was added mCPBA (0.143 g, 0.82 mmol) at 0 °C. The mixture was gradually warmed to RT and stirred for 3h. Then the reaction mixture was quenched with Aq. NaHCO₃ solution, extracted with ethyl acetate, organic portion was washed with water, dried over Na2SO4 and concentrated. The crude compound was purified by preparative TLC using 30% ethyl acetate in hexane to afford the pure intermediate- 3C (0.035 g, 20.2%). LC-MS: 418.9 [M+H]⁺. Step- 3: Synthesis of 2-((R)-3-(1-(7-(((R)-1-(2,4-dichlorophenyl)ethyl)amino)-6- fluorobenzo[d]thiazol-2-yl)azetidin-3-yl)piperidin-1-yl)ethan-1-ol A stirred solution of intermediate 3C (0.020 g, 0.108 mml) in DMF (1 mL), intermediate-I-4 and dioxane (1 mL), was added CsF (0.033 g, 0.21 mmol) and stirred at 100 °C for 2h. The reaction mixture was cooled to RT, added water, extracted with ethyl acetate, and the organic portion was dried over Na2SO4 and concentrated. The crude compound was purified by preparative TLC using 10% methanol in DCM to afford pure title compound-3 (0.015 g, 39.8%). LC-MS: 523.2 [M+H]⁺; ¹H-NMR (400 MHz, CD3OD-d4) δ 7.48 (d, 1H), 7.39 (d, 1H), 7.26-7.23 (dd, 1H), 7.01-6.96 (m, 1H), 6.88-6.84 (m, 1H), 5.29 (q, 1H), 4.22-4.15 (m, 2H), 3.93 (q, 2H), 3.71 (t, 2H), 2.93 (t, 2H), 2.7-2.6 (m, 1H), 2.55 (t, 2H), 2.1-2 (m, 1H), 1.9-1.4 (m, 4H), 1.56 (d, 3H), 0.95-0.89 (m, 2H). The below compounds were prepared using a similar procedure described in the synthesis of Example-1 or Example-3 with appropriate variations in coupling methods, reactants, quantities of reagents, and solvents. The characterization data of the compounds are summarized herein the below table-D. Table-D: Interme- Comp. Route of Structure diates Spectral data No. synthesis used LC-MS: 489.3 [M+H]⁺; 1H-NMR (400 MHz, CD3OD-D4) δ 7.49-7.45 (dd, 2H), 7.25-7.22 (dd, 1H), 6.86 (t, 1H), 6.60- 6.58 (dd, 1H), 6.19-6.17 (dd, 1H), 5.13-5.09 (m, I-2 & 1H), 4.33-4.26 (m, 2H), Ex-1 I-4 4.04-3.95 (m, 2H), 3.72 (t, 2H), 2.96-2.94 (m, 2H), 2.68-2.62 (m, 1H), 2.58 (t, 2H), 2.12-2.05 (m, 1H), 1.91-1.74 (m, 3H), 1.70-1.64 (m, 1H), 1.53 (d, 3H), 1.00-0.92 (m, 2H). LC-MS: 507.3 [M+H]⁺; 1H-NMR (400 MHz, DMSO- d6) δ 6.71 (d, 1H), 6.65 (d, 1H), 6.50- 6.47 (dd, 1H), 6.30-6.24 (dd, 1H), 5.79-5.75 (dd, 1H), 4.61-4.56 (m, 1H), 3.71 (t, 1H), 3.62 (t, 1H), A-2 3.48 (t, 1H), 3.33 (t, 1H), Ex-1 & I-4 3.13 (t, 1H), 2.90-2.86 (m, 1H), 2.80-2.77 (m, 1H), 2.48-2.46 (m, 3H), 2.20-2.14 (m, 1H), 2.05- 1.90 (m, 2H), 1.51-1.40 (m, 1H), 1.29-1.25 (m,1H), 1.15-1.08 (m, 2H), 0.77 (d, 3H), 0.45- 0.40 (m, 1H). LC-MS: 523.4 [M+H]⁺; 1H-NMR (400 MHz, CD3OD-D4) δ 7.48-7.45 (dd, 2H), 7.29-7.26 (dd, 1H), 6.53 (d, 1H), 6.18 (d, 1H), 5.11-5.08 (m, 1H), 4.33-4.24 (m, 2H), A-3 4.04-4.02 (m, 1H), 3.98- Ex-1 & I-4 3.94 (m, 1H), 3.73-3.70 (m, 2H), 2.98-2.91 (m, 2H), 2.70-2.60 (m, 1H), 2.59-2.53 (m, 2H), 2.13- 2.02 (m, 2H), 1.93-1.82 (m, 1H), 1.79-1.72 (m, 2H), 1.71-1.61 (m, 2H), 1.53 (d, 3H). LC-MS: 503.3 [M+H]⁺; 1H-NMR (400 MHz, CD3OD- D4) δ 7.51-7.46 (dd, 2H), 7.29-7.26 (dd, 1H), 6.46 (s, 1H), 6.31 (s, 1H), 5.18-5.13 (m, 1H), 4.64-4.53 (m, 2H), 4.43- A-1 4.32 (m, 2H), 3.97-3.93 Ex-1 & I-4 (m, 2H), 3.72-3.61 (m, 2H), 3.31-3.29 (m, 2H), 3.05-2.87 (m, 2H), 2.81- 2.74 (m, 1H), 2.41-2.31 (m, 1H), 2.26 (s, 3H), 2.13-2.05 (m, 1H), 1.99- 1.89 (m, 2H), 1.55 (d, 3H), 1.32-1.22 (m, 1H). LC-MS: 539.1 [M+H]⁺; 1H-NMR (400 MHz, CD3OD-D4) δ 7.46 (d, 1H), 7.35 (d, 1H), 7.27- 7.24 (dd, 1H), 6.58 (s, 1H), 5.49-5.44 (m, 1H), A-4 4.24 (t, 1H), 4.16 (t, 1H), Ex-1 & I-4 3.95 (t, 1H), 3.78 (t, 1H), 3.71 (t, 2H), 2.99-2.86 (m, 2H), 2.65-2.53 (m, 3H), 2.36 (s, 3H), 2.11- 2.03 (m, 1H), 1.88-1.71 (m, 4H), 1.69-1.63 (m, 1H), 1.60 (d, 3H). LC-MS : 503.1 [M+H]⁺ ; 1H-NMR (400 MHz, CD₃OD-d₄) δ 7.44 (d, 1H), 7.40-7.38 (m, 1H), 7,24-7.21 (dd, 1H), 6.89 (d, 1H), 6.55 (d, 1H), 5.42-5.4 (m, 1H), 4.21 (t, A-5 Ex-1 1H), 4.13 (t, 1H), 3.93- & I-4 3.89 (m, 1H), 3.76-7,71 (m, 3H) 2.96-2.9 (m, 2H), 2.5 (t, 3H), 2.34 (s, 3H), 2.15-2.05 (m, 1H), 1.8-1.75 (m, 4H), 1.63- 1.62 (m, 2H), 1.58 (d, 3H). LC-MS : 539.2 [M+H]⁺ ; 1H-NMR (400 MHz, B-2 & Ex-3 CD₃OD-d₄) δ 7.43-7.41 I-4 (m, 2H), 7.28-7.24 (m, 2H), 6.92 (d, 1H), 5.33- 5.32 (m, 1H), 4.23-4.15 (m, 2H), 3.93-3.88 (m, 2H), 3.72 (t, 2H), 2.93 (t, 2H), 2.75-2.6, (m, 1H), 2.55 (t, 2H), 2.06-2.03 (m, 1H), 1.9-1.72 (m, 4H), 1.61 (d, 3H), 0.95- 0.9 (m, 2H). LC-MS : 564.2 [M+H]⁺ ; 1H-NMR (400 MHz, CD3OD-d4) δ 7.47 (d, 1H), 7.38 (d, 1H), 7.27- 7.25 (dd, 1H), 7.11 (d, 1H), 6.60 (d, 1H), 5.50- 5.46 (m, 1H), 4.25 (t, I-1 & 1H), 4.20 (t, 1H), 3.98- Ex-1 I-7 3.94 (m, 1H), 3.81-3.77 (m, 1H), 3.37-3.34 (m, 3H), 2.94-2.85 (m, 2H), 2.67-2.58 (m, 1H), 2.50 (t, 2H), 2.25-2.15 (m, 1H), 2.08-2.02 (m, 1H), 1.96 (s, 3H), 1.83-1.70 (m, 4H), 1.31 (d, 3H). LC-MS : 563.15 [M+H]⁺ ; ¹H-NMR (400 MHz, CD3OD-d4) δ 7.46 (d, 1H), 7.39 (d, 1H), 7.28- I-1 & 7.25 (dd, 1H), 7.11 (d, Ex-1 I-5 1H), 6.60 (d, 1H), 5.49- 5.44 (m, 1H), 4.25 (t, 1H), 4.17 (t, 1H), 4.03- 3.93 (m, 3H), 3.45-3.39 (m, 2H), 3.05-2.91 (m, 2H), 2.68-2.51 (m, 2H), 2.26-2.15 (m, 1H), 1.92- 1.78 (m, 6H), 1.68-1.57 (m, 6H), 0.95-0.92 (m, 2H). LC-MS : 611.1 [M+H]⁺ ; 1H-NMR (400 MHz, CD3OD-d4) δ 7.47 (d, 1H), 7.38 (d, 1H), 7.27- 7.25 (dd, 1H), 7.13 (d, 1H), 6.60 (d, 1H), 5.48- 5.46 (m, 1H), 4.25 (t, I-1 & 1H), 4.17 (t, 1H), 3.96- Ex-1 I-6 3.93 (m, 1H), 3.80-3.77 (m, 1H), 3.19-3.07 (m, 4H), 2.84-2.62 (m, 4H), 2.35-2.27 (m, 1H), 2.18- 2.15 (m, 4H), 2.03-1.96 (m, 1H), 1.83-1.72 (m, 3H), 1.63-1.58 (m, 4H), 0.99-0.90 (m, 1H). LC-MS: 600.05 [M+H]⁺; 1H-NMR (400 MHz, CD3OD-D4) δ 7.54 (d, 1H), 7.42 (d, 1H), 7.34- 7.28 (m, 2H), 6.67 (d, 1H), 5.49 (q, 1H), 4.52 (t, I-1 & Ex-1 1H), 4.43 (t, 1H), 4.33- I-8 4.3 (m, 1H), 3.76-3.73 (m, 1H), 3.67-3.49 (m, 3H), 3.36-3.32 (m, 3H), 3.07 (s, 3H), 3.05-3 (m, 1H), 2.9-7.75 (m, 1H), 3.7 (t, 1H), 2.3-22 (m, 1H), 2.15-2 (m, 1H), 2- 1.9 (m, 2H), 1.63-1.62 (d, 3H), 1.3-1,22 (m, 1H). LC-MS: 551.10 [M+H]-; 1H-NMR (40n0 MHz, CD3OD-D4) δ 7.46 (d, 1H), 7.40 (d, 1H), 7.28- 7.25 (dd, 1H), 7.12 (d, 1H), 6.61 (d, 1H), 5.52- 5.44 (m, 1H), 4.24 (t, 1H), 4.15 (t, 1H), 3.95- I-1 & Ex-1 3.92 (m, 1H), 3.80-3.76 I 10 (m,1H), 2.95-2.82 (m, 2H), 2.75-2.66 (m, 1H), 2.35 (s, 2H), 2.33-2.28 (m, 1H), 2.07-1.95 (m, 1H), 1.93-1.83 (m, 1H), 1.76-1.65 (m, 2H), 1.60 (d, 3H), 1.22-1.20 (m, 6H), 1.02-0.88 (m, 2H). LC-MS: 549.10 [M+H]⁺; 1H-NMR (400 MHz, CD3OD) δ 7.47-7.45 (dd, 1H), 7.40-7.37 (dd, 1H), 7.29-7.24 (m, 1H), 7.12 (d, 1H), 6.61-6.59 (dd, I-1 1H), 5.52-5.44 (m, 1H), Ex-1 and I- 4.29-4.23 (m, 1H), 4.22- 11 4.12 (m, 1H), 4.01-3.91 (m, 2H), 3.84-3.76 (m, 1H), 3.17-3.03 (m, 1H), 2.88-2.75 (m, 1H), 2.65- 2.52 (m, 2H), 2.24-2.09 (m, 2H), 1.92-1.88 (m, 2H), 1.85-1.74 (m, 3H), 1.62 (d, 3H), 1.58-1.52 (m, 2H), 1.39-1.32 (m, 2H). Example-4: Synthesis of 2-((R)-3-(1-(7-(((R)-1-(2,4- dichlorophenyl)ethyl)amino)thiazolo[4,5-d]pyrimidin-2-yl)azetidin-3-yl)piperidin-1- yl)ethan-1-ol (compound-17)

Step-1: (R)-N-(1-(2,4-dichlorophenyl)ethyl)-2-(methylthio)thiazolo[4,5-d]pyrimidin-7- amine To the suspension of intermediate-I-12 (0.6 g, 2.75 mmol) and (0.78 g, 4.1 mmol) in DMSO (12 mL) was added CsF (1.25 g, 8.26 mmol) and stirred the reaction mixture at RT for 2 hrs. The progress of the reaction was monitored by TLC. After the completion of reaction, the mixture was dissolved in ice-water and extracted with EtOAc (3 times) and the combined organic layer was dried over anhydrous Na₂SO₄, concentrated under high vacuum to get crude which was purified by flash chromatography on silica gel column using 30-40% EtOAc in hexane as an eluent to afford pure intermediate-17A (0.65 g, 63% yield). LC-MS: 370.85 [M+H]⁺. Step-2: N-((R)-1-(2,4-dichlorophenyl)ethyl)-2-(methylsulfinyl)thiazolo[4,5-d]pyrimidin- 7-amine To the stirred solution of (R)-N-(1-(2,4-dichlorophenyl)ethyl)-2-(methylthio)thiazolo[4,5- d]pyrimidin-7-amine (0.1 g, 0.27 mmol) in DCM (3 mL) was added m-CPBA (0.093 g, 0.53 mmol) at 0 °C and the resulting reaction mixture was stirred at RT for 1h. After the completion of reaction, the reaction mixture was quenched with saturated aq. NaHCO3 and extracted with chloroform. The organic portion was again washed with water, dried over Na₂SO₄, filtered, and concentrated to get the crude intermediate-17B (0.17 g). LC-MS: 387.0 [M+H]⁺ . Step-3: 2-((R)-3-(1-(7-(((R)-1-(2,4-dichlorophenyl)ethyl)amino)thiazolo[4,5-d]pyrimidin- 2-yl)azetidin-3-yl)piperidin-1-yl)ethan-1-ol A mixture of N-((R)-1-(2,4-dichlorophenyl)ethyl)-2-(methylsulfinyl)thiazolo[4,5-d]pyrimidin- 7-amine (0.16 g, 0.5 mmol), intermediate-I-4 in DMF (3 mL) and was added DIPEA (0.145 g, 1.18 mmol) at 0 °C and the resulting reaction mixture was allowed to reach to RT and then was stirred at 100 °C for 2h. After the completion of reaction, the reaction mixture was concentrated to get crude compound. The crude compound was purified by preparative TLC using 10% methanol in DCM to afford the pure compound-17 (0.025 g, 25%). LC-MS: 507.0 [M+H]⁺; ¹H-NMR (400 MHz, CD₃OD) δ 8.43 (s, 1H), 7.50 (d, 1H), 7.46 (d, 1H), 7.35-7.32 (m, 1H), 5.87-5.78 (bs, 1H), 4.49-4.38 (bs, 2H), 4.27-4.18 (bs, 2H), 3.97-3.91 (m, 2H), 3.74-3.59 (m, 2H), 3.31-3.28 (m, 2H), 3.05-2.94 (m, 1H), 2.91-2.82 (m, 1H), 2.80-2.71 (m, 1H), 2.37-2.25 (m, 1H), 2.12-1.88 (m, 3H), 1.64 (d, 3H), 1.34-1.22 (m, 1H). Example-5: Synthesis of 2-(2-(1-(7-(((R)-1-(2,4-dichlorophenyl)ethyl)amino)-6- fluorobenzo[d]thiazol-2-yl)azetidin-3-yl)morpholino)ethan-1-ol (Compound-18)

Step-1: Synthesis of (R)-N-(1-(2,4-dichlorophenyl)ethyl)-6-fluoro-2- (methylthio)benzo[d]thiazol-7-amine In a sealed tube, intermediate-I-9 (0.5 g, 1.80 mmol) and (R)-1-(2,4-dichlorophenyl)ethan-1- amine (0.51 g, 2.70 mmol) were taken, dissolved using toluene (15 mL) and stirred at RT. Later, argon gas was purged for 5 minutes, then BINAP (0.22 g, 0.36 mmol), Pd2(dba)3 (0.29 g, 0.36 mmol) and sodium tertiary butoxide (0.35 g, 3.60 mmol) were added one followed by argon purging continued another 5 minutes. The resulting reaction mixture was stirred at 100 °C for 16h. After the completion of reaction, the reaction mixture was cooled to RT and concentrated to get the crude compound. The crude compound was purified by flash chromatography on silica gel column using 0-20% ethyl acetate in hexane as an eluent to afford the pure intermediate-3B (0.22 g, 31%). LC-MS: 388.0 [M+H]⁺. Step-2: Synthesis of N-((R)-1-(2,4-dichlorophenyl)ethyl)-6-fluoro-2- (methylsulfinyl)benzo[d]thiazol-7-amine To the stirred solution of (R)-N-(1-(2,4-dichlorophenyl)ethyl)-6-fluoro-2- (methylthio)benzo[d]thiazol-7-amine (0.2 g, 0.51 mmol) in dichloromethane (5 mL) was added m-CPBA (0.15 g, 0.76 mmol) at 0 °C and the resulting reaction mixture was stirred at RT for 2 h. After the completion of reaction, the reaction mixture was quenched with saturated aq. NaHCO₃ solution and extracted with CH₂Cl₂ (2 times). The organic layer was again washed with water, dried over anhydrous Na2SO4, filtered, and concentrated to get the crude intermediate-18A (0.24 g). LC-MS: 403.85 [M+H]⁺. Step-3: Synthesis of 2-(2-(1-(7-(((R)-1-(2,4-dichlorophenyl)ethyl)amino)-6- fluorobenzo[d]thiazol-2-yl)azetidin-3-yl)morpholino)ethan-1-ol To a solution of N-((R)-1-(2,4-dichlorophenyl)ethyl)-6-fluoro-2- (methylsulfinyl)benzo[d]thiazol-7-amine (0.2 g, 0.49 mmol) and I-14 (0.25 g, 0.99 mmol) in DMSO (3 mL) and was added CsF (0.24 g, 1.56 mmol) at 0 °C and the resulting reaction mixture was allowed to reach to RT and stirred at 100 °C for 16 h. After the completion of reaction, the reaction mixture was cooled to RT, quenched with saturated NH4Cl solution, extracted with 10% MeOH in CH₂Cl₂. The organic layer was dried over anhydrous Na₂SO₄, filtered, and concentrated under reduced pressure to get crude compound which was purified by preparative TLC using 15% methanol in CH2Cl2 to afford the title compound-18 (0.1 g, 34%). LC-MS: 525.0 [M+H]⁺; NMR (400 MHz, CD₃OD) δ 7.49-7.46 (m, 1H), 7.40-7.39 (dd, 1H), 7.27-7.24 (dd, 1H), 7.01-6.96 (m, 1H), 6.88-6.85 (m, 1H), 5.30-5.25 (m, 1H), 4.18-4.10 (m, 3H), 4.03-4.01 (m, 1H), 3.93-3.90 (m, 1H), 3.76-3.70 (m, 4H), 2.98-2.92 (m, 1H), 2.89- 2.79 (m, 2H), 2.56 (t, 2H), 2.27-2.19 (m, 1H), 1.92-1.85 (m, 1H), 1.56 (d, 3H). This racemic mixture was separated by using chiral HPLC and obtained both the isomers. The details of the method are as follows. Column: i CELLULOSE-C (250mmx4.6mm, 5µ) Mobile phase: A: n-Hexane B: 0.1% DEA [ETOH:MEOH (80:20)] Flow rate: 1 mL/min. 2-((R)-2-(1-(7-(((R)-1-(2,4-dichlorophenyl)ethyl)amino)-6-fluorobenzo[d]thiazol-2- yl)azetidin-3-yl)morpholino)ethan-1-ol (Isomer-1 of compound 18) (Compound-19): LC- MS: 525.0 [M+H]⁺; ¹H-NMR (400 MHz, CD3OD) δ 7.48 (d, 1H), 7.40 (d, 1H), 7.27-7.24 (dd, 1H), 7.01-6.96 (m, 1H), 6.88-6.85 (m, 1H), 5.30-5.25 (m, 1H), 4.19-4.08 (m, 3H), 4.05-4.01 (m, 1H), 3.94-3.88 (m, 1H), 3.76-3.68 (m, 4H), 2.95-2.92 (m, 1H), 2.89-2.79 (m, 2H), 2.56 (t, 2H), 2.28-2.20 (m, 1H), 1.92-1.85 (m, 1H), 1.57 (d, 3H). HPLC: 97.7% and chiral HPLC: 98.5%. 2-((S)-2-(1-(7-(((R)-1-(2,4-dichlorophenyl)ethyl)amino)-6-fluorobenzo[d]thiazol-2- yl)azetidin-3-yl)morpholino)ethan-1-ol (Isomer-2 of compound 18) (Compound-20): LC- MS: 525.0 [M+H]⁺; ¹H-NMR (400 MHz, CD3OD) δ 7.49 (d, 1H), 7.40 (d, 1H), 7.27-7.24 (dd, 1H), 7.01-6.96 (m, 1H), 6.88-6.85 (m, 1H), 5.31-5.24 (m, 1H), 4.21-4.10 (m, 3H), 4.05-4.00 (m, 1H), 3.95-3.88 (m, 1H), 3.78-3.70 (m, 4H), 2.98-2.90 (m, 1H), 2.89-2.79 (m, 2H), 2.56 (t, 2H), 2.28-2.20 (m, 1H), 1.92-1.85 (m, 1H), 1.56 (d, 3H). HPLC: 99.06% and chiral HPLC: 98.95%. The below compounds were prepared using a similar procedure described in the synthesis of Example-5 with appropriate variations in coupling methods, reactants, quantities of reagents, and solvents. The characterization data of the compounds are summarized herein the below table-E. Table-E: Comp. Route of Interme- Structure Spectral data No. synthesis diates used LC-MS: 537.1 [M+H]⁺; 1H-NMR (400 MHz, CD₃OD) δ 7.48 (d, 1H), 7.40 (d, 1H), 7.27-7.24 B-1 and 21 Ex-5 (dd, 1H), 7.02-6.97 (m, I-15 1H), 6.89-6.85 (m, 1H), 5.32-5.24 (m, 1H), 4.24- 4.17 (m, 2H), 3.93-3.89 (m, 2H), 3.68-3.59 (m, 1H), 3.55-3.48 (m, 1H), 2.95-2.78 (m, 3H), 2.76- 2.64 (m, 1H), 2.52-2.33 (m, 1H), 2.24-2.02 (m, 1H),1.98-1.89 (m, 1H), 1.87-1.75 (m, 2H), 1.72- 1.60 (m, 1H), 1.56 (d, 3H), 1.09 (d, 3H), 1.04- 0.92 (m, 1H). LC-MS: 537.05 [M+H]+; 1H-NMR (400 MHz, CD3OD) δ 7.48 (d, 1H), 7.40 (d, 1H), 7.27- 7.24 (dd, 1H), 7.03-6.96 (m, 1H), 6.88-6.85 (m, 1H), 5.32-5.24 (m, 1H), 4.26-4.17 (m, 2H), 3.95- Isomer-1 of compound 21 3.88 (m, 2H), 3.64-3.59 Ex-5 - (m, 1H), 3.53-3.47 (m, Column: CELLULOSE-4 1H), 2.95-2.77 (m, 3H), (250mmx4.6mm, 5µ); 2.73-2.65 (m, 1H), 2.39- Mobile phase: A: n-Hexane 2.28 (m, 1H), 2.24-2.03 B: 0% DEA [ETOH:MeOH (m, 1H),1.98-1.88 (m, (80:20)] 1H), 1.86-1.75 (m, 2H), Flow rate: 1.0 ml\min. 1.68-1.60 (m, 1H), 1.56 (d, 3H), 1.09 (d, 3H), 1.03-0.92 (m, 1H). LC-MS: 537.05 [M+H]⁺; 1H-NMR (400 MHz, CD₃OD) δ 7.48 (d, 1H), Ex-3 - 7.40 (d, 1H), 7.27-7.24 (dd, 1H), 7.03-6.97 (m, Isomer-2 of compound 21 1H), 6.88-6.85 (m, 1H), 5.32-5.25 (m, 1H), 4.24- Column: CELLULOSE-4 4.17 (m, 2H), 3.93-3.88 (250mmx4.6mm, 5µ); (m, 2H), 3.68-3.63 (m, Mobile phase: A: n-Hexane 1H), 3.55-3.49 (m, 1H), B: 0% DEA [ETOH:MeOH 2.96-2.79 (m, 3H), 2.72- (80:20)] 2.64 (m, 1H), 2.55-2.46 Flow rate: 1.0 ml\min. (m, 1H), 2.12-2.01 (m, 1H),1.93-1.78 (m, 3H), 1.74-1.60 (m, 1H), 1.57(d, 3H), 1.11 (d, 3H), 1.05-0.91 (m, 1H). LC-MS: 551.10 [M+H]⁺; 1H-NMR (400 MHz, CD₃OD) δ 7.48 (d, 1H), 7.40 (d, 1H), 7.27-7.24 (dd, 1H), 7.02-6.96 (m, 1H), 6.88-6.84 (m, 1H), 5.32-5.25 (m, 1H), 4.23- B-1 and 4.15 (m, 2H), 3.91-3.89 Ex-5 I-10 (m, 2H), 2.92-2.84 (m, 2H), 2.82-2.64 (m, 1H), 2.31 (s, 2H), 2.28-2.19 (m, 1H), 2.02-1.88 (m, 2H), 1.70-1.61 (m, 2H), 1.56 (d, 3H), 1.21-1.19 (m, 6H), 1.03-0.89 (m, 2H). LC-MS: 549.10 [M+H]⁺; 1H-NMR (400 MHz, CD₃OD) δ 7.49 (d, 1H), B-1 and 7.40 (d, 1H), 7.27-7.24 Ex-5 I-11 (dd, 1H), 7.02-6.97 (m, 1H), 6.89-6.85 (m, 1H), 5.32-5.24 (m, 1H), 4.28- 4.18 (m, 2H), 3.99-3.92 (m, 2H), 2.75-2.63 (m, 2H), 2.08-1.98 (m, 2H), 1.89-1.79 (m, 2H), 1.77- 1.70 (m, 1H), 1.58 (d, 3H), 1.38-1.29 (m, 4H), 0.95-0.88 (m, 1H), 0.82- 0.76 (m, 2H), 0.58-0.55 (m, 2H). LC-MS: 563.1 [M+H]⁺; 1H-NMR (400 MHz, DMSO-D6) δ 7.58-7.51 (m, 2H), 7.40-7.37 (dd, 1H), 7.03-6.97 (m, 1H), 6.84-6.80 (m, 1H), 6.30 (s, 1H), 5.83-5.80 (m, B-1 and 1H), 5.25-5.06 (m, 1H), Ex-5 I-16 4.14 (t, 2H), 3.86-3.79 (m, 2H), 2.06-1.96 (m, 1H), 1.86-1.74 (m, 2H), 1.70-1.63 (m, 1H), 1.50 (d, 3H), 1.28-1.22 (m, 4H), 1.20-1.14 (m, 1H), 0.98-0.84 (m, 3H), 0.80- 0.72 (m, 2H). LC-MS: 537.1 [M+H]⁺; 1H-NMR (400 MHz, CD3OD) δ 7.48 (d, 1H), 7.42-7.39 (m, 1H), 7.27- B-1 and 7.24 (dd, 1H), 7.02-6.97 Ex-5 I-17 (m, 1H), 6.89-6.85 (m, 1H), 5.32-5.24 (m, 1H), 4.26-4.18 (m, 2H), 3.96- 3.88 (m, 2H), 3.81-3.72 (m, 2H), 3.16-3.03 (m, 1H), 2.90-2.72 (m, 2H), 2.70-2.62 (m, 1H), 2.58- 2.40 (m, 1H), 2.09-1.98 (m,1H), 1.96-1.74 (m, 3H), 1.70-1.62 (m, 1H), 1.57 (d, 3H), 1.22 (d, 3H), 1.19-1.12 (m, 1H). LC-MS: 537.05 [M+H]⁺; 1H-NMR (400 MHz, CD₃OD) δ 7.48 (d, 1H), 7.40 (d, 1H), 7.27-7.24 (dd, 1H), 7.03-6.97 (m, 1H), 6.88-6.85 (m, 1H), 5.32-5.25 (m, 1H), 4.24- Isomer-1 of compound-27 4.17 (m, 2H), 3.93-3.88 Ex-5 - (m, 2H), 3.68-3.63 (m, Column: CELLULOSE-4 1H), 3.55-3.49 (m, 1H), (250mmx4.6mm, 5µ); 2.96-2.79 (m, 3H), 2.72- Mobile phase: A: n-Hexane 2.64 (m, 1H), 2.55-2.46 B: 0% DEA [ETOH:MeOH (m, 1H), 2.12-2.01 (m, (80:20)] 1H),1.93-1.78 (m, 3H), Flow rate: 1.0 ml\min. 1.74-1.60 (m, 1H), 1.57(d, 3H), 1.11 (d, 3H), 1.05-0.91 (m, 1H). LC-MS: 537.1 [M+H]⁺; 1H-NMR (400 MHz, CD3OD) δ 7.49 (d, 1H), 7.40 (d, 1H), 7.27-7.24 (dd, 1H), 7.02-6.97 (m, Ex-5 - Isomer-2 of compound-27 1H), 6.88-6.85 (m, 1H), 5.32-5.24 (m, 1H), 4.23- Column: CELLULOSE-4 4.18 (m, 2H), 3.94-3.88 (250mmx4.6mm,5µ,); (m, 2H), 3.71 (t, 2H), Mobile phase: A: n-Hexane 2.90-2.67 (m, 3H), 2.56- B: 0% DEA [ETOH:MeOH 2.45 (m, 1H), 2.03-1.95 (80:20)] (m, 1H), 1.89-1.80 (m, Flow rate: 1.0 ml\min. 1H), 1.68-1.59 (m, 2H), 1.57(d, 3H), 1.40-1.38 (m, 3H), 1.14 (d, 3H). LC-MS: 523.1 [M+H]⁺; 1H-NMR (400 MHz, CD3OD) δ 7.48 (d, 1H), 7.40 (d, 1H), 7.27-7.24 (dd, 1H), 7.02-6.96 (m, 1H), 6.88-6.84 (m, 1H), 5.32-5.24 (m, 1H), 4.23- 30 Ex-5 B-1and I-19 4.17 (m, 2H), 3.92-3.86 (m, 2H), 3.71 (t, 2H), 3.08-3.00 (m, 2H), 2.71- 2.62 (m, 1H), 2.56 (t, 2H), 2.18-2.07 (m, 2H), 1.79-1.72 (m, 2H), 1.67- 1.59 (m, 1H), 1.56 (d, 3H), 1.38-1.29 (m, 2H). Example-6: Synthesis of 2-((R)-3-(1-(7-(((R)-1-(2,4-dichlorophenyl)ethyl)amino)-6- fluorothiazolo[4,5-b]pyridin-2-yl)azetidin-3-yl)piperidin-1-yl)ethan-1-ol (compound-31)

Step-1: Synthesis of (R)-N-(1-(2,4-dichlorophenyl)ethyl)-6-fluoro-2- (methylthio)thiazolo[4,5-b]pyridin-7-amine In a sealed tube, intermediate I-13 (0.35 g, 1.07 mmol) and (R)-1-(2,4-dichlorophenyl)ethan-1- amine (0.31 g, 1.61 mmol) were taken, dissolved using toluene (10 mL) and stirred at RT. Later, argon gas was purged for 5 minutes, then xantphos (0.124 g, 0.21 mmol), Pd2(dba)3 (0.098 g, 0.1 mmol) and sodium tert-butoxide (0.2 g, 2.14 mmol) were added one followed by another and the argon purging was continued another for 5 minutes. The resulting reaction mixture was stirred at 100 °C for 12h. After the completion of reaction, the reaction mixture was cooled to RT, diluted with ethyl acetate, filtered the RM through celite, concentrated the filtrate to get the crude compound. The crude compound was purified by flash chromatography on silica gel column using 12-16% ethyl acetate in hexane as an eluent to afford the pure intermediate-31A (0.35 g, 84%). LC-MS: 387.9 [M+H]⁺. Step-2: Synthesis of (R)-N-(1-(2,4-dichlorophenyl)ethyl)-6-fluoro-2- (methylsulfonyl)thiazolo[4,5-b]pyridin-7-amine To the stirred solution of (R)-N-(1-(2,4-dichlorophenyl)ethyl)-6-fluoro-2- (methylthio)thiazolo[4,5-b]pyridin-7-amine (0.32 g, 0.51 mmol) in dichloromethane (20 mL) was added m-CPBA (0.43 g, 2.47 mmol) at 0 °C and the resulting reaction mixture was stirred at RT for 16h. After the completion of reaction, the reaction mixture was quenched with saturated aq. NaHCO₃ and extracted with DCM. The organic portion was again washed with water, dried over Na₂SO₄, filtered, and concentrated to get the crude intermediate-31B (0.3 g). LC-MS: 419.85 [M+H]⁺ . Step-3: 2-((R)-3-(1-(7-(((R)-1-(2,4-dichlorophenyl)ethyl)amino)-6-fluorothiazolo[4,5- b]pyridin-2-yl)azetidin-3-yl)piperidin-1-yl)ethan-1-ol A mixture of (R)-N-(1-(2,4-dichlorophenyl)ethyl)-6-fluoro-2- (methylsulfonyl)thiazolo[4,5-b]pyridin-7-amine (0.3 g, 0.71 mmol), intermediate-I-4 (0.32 g, 1.43 mmol) in DMSO (10 mL) and was added CsF (0.32 g, 2.14 mmol) at 0 °C and the resulting reaction mixture was allowed to reach to RT and then was stirred at 100 °C for 1h. After the completion of reaction, the reaction mixture was concentrated to get crude compound. The crude compound was purified by preparative TLC using 10% methanol in DCM to afford the pure compound-31 (0.03 g, 8%). LC-MS: 524.1 [M+H]⁺; ¹H-NMR (400 MHz, CD₃OD) δ 7.90 (d, 1H), 7.51 (d, 1H), 7.42 (d, 1H), 7.31-7.28 (dd, 1H), 5.44-5.38 (m, 1H), 4.24-4.14 (m, 2H), 3.94-3.88 (m, 2H), 3.71 (t, 2H), 2.94 (t, 2H), 2.71-2.62 (m, 1H), 2.60-2.55 (m, 2H), 2.14-2.03 (m, 1H), 1.96-1.86 (m, 1H), 1.84-1.72 (m, 3H), 1.70-1.64 (m, 1H), 1.62 (d, 3H), 0.99-0.92 (m, 1H). Example-7: Synthesis of 2-((3R)-3-(1-(7-(((R)-1-(2,4-dichlorophenyl)ethyl)amino)-6- fluorobenzo[d]thiazol-2-yl)azetidin-3-yl)-2,6-dimethylpiperidin-1-yl)ethan-1-ol (compound-32)

Step-1: Synthesis of (R)-N-(1-(2,4-dichlorophenyl)ethyl)-6-fluoro-2- (methylsulfonyl)benzo[d]thiazol-7-amine To the stirred solution of intermediate-3B (0.2 g, 0.51 mmol) in dichloromethane (5 mL) was added m-CPBA (0.19 g, 1.02 mmol) at 0 °C and the resulting reaction mixture was stirred at RT for 6 h. After the completion of reaction, the reaction mixture was quenched with saturated aq. NaHCO3 solution and extracted with CH2Cl2 (2 times). The organic layer was again washed with water, dried over anhydrous Na₂SO₄, filtered, and concentrated to get the crude intermediate-3C (0.2 g). LC-MS: 418.9 [M+H]⁺. Step-2: Synthesis of ethyl 2-(3-(1-(7-(((R)-1-(2,4-dichlorophenyl)ethyl)amino)-6- fluorobenzo[d]thiazol-2-yl)azetidin-3-yl)-2,6-dimethylpiperidin-1-yl)-2-oxoacetate To a solution of (R)-N-(1-(2,4-dichlorophenyl)ethyl)-6-fluoro-2- (methylsulfonyl)benzo[d]thiazol-7-amine (0.45 g, 1.07 mmol) and intermediate-I-18 (0.48 g, 1.79 mmol) in DMF (10 mL) and was added CsCO3 (1.05 g, 3.21 mmol) at 0 °C and the resulting reaction mixture was allowed to stir at RT for 12 h. After the completion of reaction, the reaction mixture was quenched with saturated NH₄Cl solution, extracted with 10% MeOH in CH2Cl2. The organic layer was dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure to get crude compound which was purified by flash column chromatography with 15% methanol in CH₂Cl₂ as eluent to afford the intermediate-32A (0.5 g, 76% yield). LC-MS: 607.2 [M+H]⁺. Step-3: Synthesis of 2-((3R)-3-(1-(7-(((R)-1-(2,4-dichlorophenyl)ethyl)amino)-6- fluorobenzo[d]thiazol-2-yl)azetidin-3-yl)-2,6-dimethylpiperidin-1-yl)ethan-1-ol To a solution of ethyl 2-(3-(1-(7-(((R)-1-(2,4-dichlorophenyl)ethyl)amino)-6- fluorobenzo[d]thiazol-2-yl)azetidin-3-yl)-2,6-dimethylpiperidin-1-yl)-2-oxoacetate (0.48 g, 0.79 mmol) in anhydrous THF (10 mL) 1 M LAH solution (0.87 mL, 0.87 mmol) was added slowly dropwise at 0 °C and the resulting reaction mixture was allowed to reach to RT for 1h. After the completion of reaction, the reaction mixture was quenched with saturated NH4Cl solution, extracted with 10% MeOH in CH₂Cl₂. The organic layer was dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure to get crude compound which was purified by flash column chromatography using (7-10%) MeOH/DCM to afford pure title compound-32 (0.3 g, 73%). LC-MS: 551.2 [M+H]⁺. Although the present application has been illustrated by certain of the preceding examples, it is not to be construed as being limited thereby; but rather, the present application encompasses the generic area as hereinbefore disclosed. For example, the compounds provided below in table-F which can be prepared by following similar procedure as described in above Schemes/Examples with suitable modifications known to the one ordinary skilled in the art are also included in the scope of the present application: Table-F: Comp. Comp. Structure Structure No. No. 33. 34. ; ; 35. 36. ; ; 47. 48. ; ; 49. 50. ; ; 51. 52. ; and . Biology: β-Arrestin Recruitment Assay Protocol CHO-K1 CCR4 β-Arrestin cells were seeded and incubated overnight at 37°C in a CO₂ incubator for adherence. Next day, cells were pretreated with various concentrations of CCR4 modulators for 30 mins at 37°C. The cells were stimulated with recombinant human CCL22 (10nM) and further incubated for 90 mins. Working detection solution was added and incubated at room temperature for 1 hour after which the chemiluminescent signal was read using a luminometer. Exemplary compounds of the present application were screened by the above- mentioned assay and the results were tabulated. The CCR4 % inhibition values for certain exemplary compounds at 5µM are compiled in the table-G below. Table-G: % inhibition values of exemplary compounds Comp. % inhibition Comp. % inhibition No. (% E-Max) at 5 µM No. (% E-Max) at 5 µM 1 102% 17 103% 2 103% 18 92% 3 106% 19 65% 4 97% 20 96% 5 97% 21 106% 6 96% 22 103% 7 102% 23 104% 8 105% 24 103% 9 103% 25 104% 10 103% 26 53% 11 103% 27 104% 12 104% 28 104% 13 102% 29 103% 14 103% 30 96% 15 103% 31 102% 16 100% 32 102% The CCR4 antagonistic activity IC50 values of the selected compounds are set forth below in table-H, wherein “A” refers to an IC50 value less than 0.01 μM, “B” refers to an IC50 value in range of 0.01 μM to 0.1 μM (both inclusive) and “C” refers to an IC₅₀ value greater than 0.1 μM. Table-H: IC50 values of exemplary compounds Comp. IC50 (µM) Comp. IC50 (µM) No. in range No. in range 1_{B 17 A} 2 B 18 C 3 A 19 -- 4 B 20 B 5 B 21 A 6 C 22 A 7 B 23 A 8 A 24 A 9 A 25 A 10 A 26 A 11 A 27 A 12 C 28 A 13 B 29 A 14 B 30 C 15 C 31 A 16 C 32 B Incorporation by Reference All publications and patents mentioned herein are hereby incorporated by reference in their entirety as if each individual publication or patent were specifically and individually indicated to be incorporated by reference. In case of conflict, the present application, including any definitions herein, will control. Equivalents While specific embodiments of the subject disclosure have been discussed, the above specification is illustrative and not restrictive. Many variations of the disclosure will become apparent to those skilled in the art upon review of this specification and the claims below. The full scope of the disclosure should be determined by reference to the claims, along with their full scope of equivalents, and the specification, along with such variations.

Claims

We claim: 1. A compound of formula (I-1):

or a pharmaceutically acceptable salt or a stereoisomer thereof; wherein, W1 is C, N or O; X1 and X2 are each independently CH, N, NRx, O or S; X₃, X₄ and X₅ are each independently CH or N; R_x is hydrogen or alkyl; R1 at each occurrence is independently alkyl, alkenyl, alkynyl, halo, cyano, amino, nitro, -OR1a, -C(O)R1b or cycloalkyl; wherein each of alkyl, alkenyl, alkynyl and cycloalkyl is optionally substituted with one or more substituents independently selected from halo, hydroxy and alkoxy; R2 and R2' are each independently hydrogen or alkyl; R₃ is hydrogen or alkyl; R₄ at each occurrence is independently alkyl, alkenyl, alkynyl, halo, cyano, amino, nitro, -OR4a, -C(O)R4b or cycloalkyl; wherein each of alkyl, alkenyl, alkynyl and cycloalkyl is optionally substituted with one or more substituents independently selected from hydroxy, halo and alkoxy; each R1a and R4a is independently hydrogen, alkyl, haloalkyl, cycloalkyl or heterocycloalkyl; R₅ at each occurrence is independently halo, alkyl, haloalkyl, alkoxy or -C(O)R_5a; each R1b, R4b and R5a is independently hydrogen, alkyl, amino, alkylamino, hydroxy, haloalkyl, cycloalkyl or heterocycloalkyl; R₆ is alkyl, heterocycloalkyl or -C(O)R_6c; wherein each alkyl and heterocycloalkyl is optionally substituted with one or more substituents independently selected from hydroxy, - NR6aR6b, halo and cycloalkyl, wherein the cycloalkyl is optionally substituted with one or more substituents independently selected from hydroxy, halo, alkyl, acyl and alkoxy; each R_6a and R_6b is independently hydrogen, alkyl, acyl or alkylsulfonyl; R6c is independently alkyl, heterocycloalkyl or cycloalkyl, wherein each alkyl, heterocycloalkyl and cycloalkyl is optionally substituted with one or more substituents independently selected from hydroxy, halo, alkyl, acyl and alkoxy; ‘m’ is an integer from 0 to 5; ‘n’ is an integer from 0 to 3; ‘j’ is an integer from 0 to 4; and ‘k’ is an integer from 0 to 2.

2. The compound according to claim 1, having a formula (I):

or a pharmaceutically acceptable salt or a stereoisomer thereof.

3. The compound according to claim 1, having formula (IA-1), (IB-1), (IC-1), (ID-1), (IE- 1), (IF-1) & (IG-1): or a pharmaceutically acceptable salt or a stereoisomer thereof; wherein ‘p’ is an integer from 1 to 8.

4. The compound according to any one of claims 1 to 3, wherein the ring represented by

, wherein the asterisk mark represents the point of attachment with azetidine ring.

5. The compound according to any one of claims 1 to 4, wherein the ring represented by

attachment with azetidine ring.

6. The compound according to any one of claims 1 to 5, wherein the ring represented by

ring.

7. The compound according to any one of claims 1 to 5, wherein the ring represented by or

.

8. The compound according to any one of claims 1 to 3, wherein X1 is NRx, O or S, and X2 is CH or N.

9. The compound according to any one of claims 1 to 3, wherein X₁ is O or S, and X₂ is N.

10. The compound according to any one of claims 1 to 3, wherein R1 at each occurrence is halo.

11. The compound according to any one of claims 1 to 3, wherein R₂ is alkyl and R₂' is hydrogen.

12. The compound according to any one of claims 1 to 3, wherein R3 is hydrogen.

13. The compound according to any one of claims 1 to 3, wherein R4 at each occurrence is selected from halo, alkyl and -OR_4a.

14. The compound according to any one of claims 1 to 3, wherein R6 is alkyl; wherein the alkyl is substituted with hydroxy.

15. The compound according to any one of claims 1 to 3, wherein, X1 and X2 are each independently N, O or S; X3, X4 and X5 are each CH or N; R₁ at each occurrence independently is alkyl or halo; R₂ is alkyl and R₂' is hydrogen; R3 is hydrogen; R4 at each occurrence independently is alkyl, halo, cyano or -OR4a; wherein the alkyl is substituted with one or more halo; R4a is alkyl or haloalkyl; R5 at each occurrence is independently halo, alkyl or haloalkyl; R₆ is alkyl; wherein, the alkyl is independently substituted with one or more hydroxy or halo; ‘m’ is an integer from 0 to 2; ‘n’ is an integer from 0 to 2; ‘j’ is 0 to 2; and ‘k’ is 1.

16. The compound according to any one of claims 1 to 15, wherein j is 0.

17. The compound according to any one of claims 1 to 15, wherein k is 1.

18. The compound according to any one of claims 1 to 15, wherein m is 2.

19. A compound selected from: Comp. No. IUPAC name 1 2-((R)-3-(1-(6-chloro-7-(((R)-1-(2,4-dichlorophenyl)ethyl)amino)benzo[d]oxazol- 2-yl)azetidin-3-yl)piperidin-1-yl)ethan-1-ol; 2 2-((R)-3-(1-(7-(((R)-1-(2,4-dichlorophenyl)ethyl)amino)benzo[d]thiazol-2- yl)azetidin-3-yl)piperidin-1-yl)ethan-1-ol; 3 2-((R)-3-(1-(6-Fluoro-7-(((R)-1-(2,4-dichlorophenyl)ethyl)amino)benzo[d]thiazol- 2-yl)azetidin-3-yl)piperidin-1-yl)ethan-1-ol; 4 2-((R)-3-(1-(7-(((R)-1-(2,4-dichlorophenyl)ethyl)amino)benzo[d]oxazol-2- yl)azetidin-3-yl)piperidin-1-yl)ethan-1-ol; 5 2-((R)-3-(1-(7-(((R)-1-(2,4-dichlorophenyl)ethyl)amino)-6-fluorobenzo[d]oxazol- 2-yl)azetidin-3-yl)piperidin-1-yl)ethan-1-ol; 6 2-((R)-3-(1-(5-chloro-7-(((R)-1-(2,4-dichlorophenyl)ethyl)amino)benzo[d]oxazol- 2-yl)azetidin-3-yl)piperidin-1-yl)ethan-1-ol; 7 2-((R)-3-(1-(7-(((R)-1-(2,4-dichlorophenyl)ethyl)amino)-5-methylbenzo[d]oxazol- 2-yl)azetidin-3-yl)piperidin-1-yl)ethan-1-ol; 8 2-((R)-3-(1-(6-chloro-7-(((R)-1-(2,4-dichlorophenyl)ethyl)amino)-5- methylbenzo[d]oxazol-2-yl)azetidin-3-yl)piperidin-1-yl)ethan-1-ol; 9 2-((R)-3-(1-(7-(((R)-1-(2,4-dichlorophenyl)ethyl)amino)-6-methylbenzo[d]oxazol- 2-yl)azetidin-3-yl)piperidin-1-yl)ethan-1-ol; 10 2-((R)-3-(1-(6-chloro-7-(((R)-1-(2,4-dichlorophenyl)ethyl)amino)benzo[d]thiazol- 2-yl)azetidin-3-yl)piperidin-1-yl)ethan-1-ol; N-(2-((R)-3-(1-(6-chloro-7-(((R)-1-(2,4- 11 dichlorophenyl)ethyl)amino)benzo[d]oxazol-2-yl)azetidin-3-yl)piperidin-1- yl)ethyl)acetamide; 12 6-chloro-N-((R)-1-(2,4-dichlorophenyl)ethyl)-2-(3-((R)-1-(tetrahydro-2H-pyran-4- yl)piperidin-3-yl)azetidin-1-yl)benzo[d]oxazol-7-amine; 13 4-((R)-3-(1-(6-chloro-7-(((R)-1-(2,4-dichlorophenyl)ethyl)amino)benzo[d]oxazol- 2-yl)azetidin-3-yl)piperidin-1-yl)tetrahydro-2H-thiopyran 1,1-dioxide; N-(2-((R)-3-(1-(6-chloro-7-(((R)-1-(2,4- dichlorophenyl)ethyl)amino)benzo[d]oxazol-2-yl)azetidin-3-yl)piperidin-1- yl)ethyl)methanesulfonamide; 1-((R)-3-(1-(6-chloro-7-(((R)-1-(2,4-dichlorophenyl)ethyl)amino)benzo[d]oxazol- 2-yl)azetidin-3-yl)piperidin-1-yl)-2-methylpropan-2-ol; 1-(((R)-3-(1-(6-chloro-7-(((R)-1-(2,4-dichlorophenyl)ethyl)amino)benzo[d]oxazol- 2-yl)azetidin-3-yl)piperidin-1-yl)methyl)cyclopropan-1-ol; 2-((R)-3-(1-(7-(((R)-1-(2,4-dichlorophenyl)ethyl)amino)thiazolo[4,5-d]pyrimidin- 2-yl)azetidin-3-yl)piperidin-1-yl)ethan-1-ol; 2-(2-(1-(7-(((R)-1-(2,4-dichlorophenyl)ethyl)amino)-6-fluorobenzo[d]thiazol-2- yl)azetidin-3-yl)morpholino)ethan-1-ol; 2-((R)-2-(1-(7-(((R)-1-(2,4-dichlorophenyl)ethyl)amino)-6-fluorobenzo[d]thiazol- 2-yl)azetidin-3-yl)morpholino)ethan-1-ol (Isomer-1 of compound 18); 2-((S)-2-(1-(7-(((R)-1-(2,4-dichlorophenyl)ethyl)amino)-6-fluorobenzo[d]thiazol- 2-yl)azetidin-3-yl)morpholino)ethan-1-ol (Isomer-2 of compound 18); 2-((R)-3-(1-(7-(((R)-1-(2,4-dichlorophenyl)ethyl)amino)-6-fluorobenzo[d]thiazol- 2-yl)azetidin-3-yl)piperidin-1-yl)propan-1-ol; (R)-2-((R)-3-(1-(7-(((R)-1-(2,4-dichlorophenyl)ethyl)amino)-6- fluorobenzo[d]thiazol-2-yl)azetidin-3-yl)piperidin-1-yl)propan-1-ol (Isomer-1 of compound 21); (S)-2-((R)-3-(1-(7-(((R)-1-(2,4-dichlorophenyl)ethyl)amino)-6- fluorobenzo[d]thiazol-2-yl)azetidin-3-yl)piperidin-1-yl)propan-1-ol (Isomer-2 of compound 21); 1-((R)-3-(1-(7-(((R)-1-(2,4-dichlorophenyl)ethyl)amino)-6-fluorobenzo[d]thiazol- 2-yl)azetidin-3-yl)piperidin-1-yl)-2-methylpropan-2-ol; 1-(((R)-3-(1-(7-(((R)-1-(2,4-dichlorophenyl)ethyl)amino)-6-fluorobenzo[d]thiazol- 2-yl)azetidin-3-yl)piperidin-1-yl)methyl)cyclopropan-1-ol; ((R)-3-(1-(7-(((R)-1-(2,4-dichlorophenyl)ethyl)amino)-6-fluorobenzo[d]thiazol-2- yl)azetidin-3-yl)piperidin-1-yl)(1-hydroxycyclopropyl)methanone; 2-(5-(1-(7-(((R)-1-(2,4-dichlorophenyl)ethyl)amino)-6-fluorobenzo[d]thiazol-2- yl)azetidin-3-yl)-2-methylpiperidin-1-yl)ethan-1-ol; 2-((2R,5R)-5-(1-(7-(((R)-1-(2,4-dichlorophenyl)ethyl)amino)-6- fluorobenzo[d]thiazol-2-yl)azetidin-3-yl)-2-methylpiperidin-1-yl)ethan-1-ol (Isomer-1 of compound 27); 2-((2S,5R)-5-(1-(7-(((R)-1-(2,4-dichlorophenyl)ethyl)amino)-6- fluorobenzo[d]thiazol-2-yl)azetidin-3-yl)-2-methylpiperidin-1-yl)ethan-1-ol (Isomer-2 of compound 27); (R)-2-(4-(1-(7-((1-(2,4-dichlorophenyl)ethyl)amino)-6-fluorobenzo[d]thiazol-2- yl)azetidin-3-yl)piperidin-1-yl)ethan-1-ol; 2-((R)-3-(1-(7-(((R)-1-(2,4-dichlorophenyl)ethyl)amino)-6-fluorothiazolo[4,5- b]pyridin-2-yl)azetidin-3-yl)piperidin-1-yl)ethan-1-ol; 2-((3R)-3-(1-(7-(((R)-1-(2,4-dichlorophenyl)ethyl)amino)-6-fluorobenzo[d]thiazol- 2-yl)azetidin-3-yl)-2,6-dimethylpiperidin-1-yl)ethan-1-ol; 2-((R)-3-(1-(7-(((R)-1-(2,4-dichlorophenyl)ethyl)amino)-6- methoxybenzo[d]oxazol-2-yl)azetidin-3-yl)piperidin-1-yl)ethan-1-ol; 2-((R)-3-(1-(7-(((R)-1-(2,4-dichlorophenyl)ethyl)amino)-6- (difluoromethoxy)benzo[d]oxazol-2-yl)azetidin-3-yl)piperidin-1-yl)ethan-1-ol; 2-((R)-3-(1-(7-(((R)-1-(2,4-dichlorophenyl)ethyl)amino)-6- (trifluoromethoxy)benzo[d]oxazol-2-yl)azetidin-3-yl)piperidin-1-yl)ethan-1-ol; 2-((R)-3-(1-(7-(((R)-1-(2,4-dichlorophenyl)ethyl)amino)-6- (trifluoromethyl)benzo[d]oxazol-2-yl)azetidin-3-yl)piperidin-1-yl)ethan-1-ol; 2-((R)-3-(1-(4-(((R)-1-(2,4-dichlorophenyl)ethyl)amino)oxazolo[5,4-c]pyridin-2- yl)azetidin-3-yl)piperidin-1-yl)ethan-1-ol; 2-((R)-3-(1-(7-(((R)-1-(2,4-dichlorophenyl)ethyl)amino)oxazolo[4,5-c]pyridin-2- yl)azetidin-3-yl)piperidin-1-yl)ethan-1-ol; 2-((R)-3-(1-(7-(((R)-1-(2,4-dichlorophenyl)ethyl)amino)oxazolo[4,5-b]pyridin-2- yl)azetidin-3-yl)piperidin-1-yl)ethan-1-ol; 2-((R)-3-(1-(6-chloro-7-(((R)-1-(2,4-dichlorophenyl)ethyl)amino)oxazolo[4,5- b]pyridin-2-yl)azetidin-3-yl)piperidin-1-yl)ethan-1-ol; 2-((R)-3-(1-(6-chloro-7-(((R)-1-(2,4-dichlorophenyl)ethyl)amino)-5- methyloxazolo[4,5-b]pyridin-2-yl)azetidin-3-yl)piperidin-1-yl)ethan-1-ol; 2-((R)-3-(1-(6-chloro-7-(((R)-1-(2,4-dichlorophenyl)ethyl)amino)benzofuran-2- yl)azetidin-3-yl)piperidin-1-yl)ethan-1-ol; 2-((R)-3-(1-(6-chloro-7-(((R)-1-(2,4-dichlorophenyl)ethyl)amino)-1-methyl-1H- indol-2-yl)azetidin-3-yl)piperidin-1-yl)ethan-1-ol; (R)-1-(2,4-dichlorophenyl)ethyl)amino)-2-(3-((R)-1-(2-hydroxyethyl)piperidin-3- yl)azetidin-1-yl)-N,N-dimethylbenzo[d]oxazole-6-carboxamide; 7-(((R)-1-(2,4-dichlorophenyl)ethyl)amino)-2-(3-((R)-1-(2- hydroxyethyl)piperidin-3-yl)azetidin-1-yl)benzo[d]oxazole-6-carboxamide; 7-(((R)-1-(2,4-dichlorophenyl)ethyl)amino)-2-(3-((R)-1-(2- hydroxyethyl)piperidin-3-yl)azetidin-1-yl)benzo[d]oxazole-6-carbonitrile; 47 3-((R)-3-(1-(6-chloro-7-(((R)-1-(2,4-dichlorophenyl)ethyl)amino)benzo[d]oxazol- 2-yl)azetidin-3-yl)pyrrolidin-1-yl)propan-1-ol; 48 2-((R)-3-(1-(7-(((R)-1-(2,4-dichlorophenyl)ethyl)amino)-6- (difluoromethyl)benzo[d]oxazol-2-yl)azetidin-3-yl)piperidin-1-yl)ethan-1-ol; 49 2-((R)-3-(1-(6-chloro-7-(((R)-1-(2,4-dichlorophenyl)ethyl)amino)benzo[d]oxazol- 2-yl)azetidin-3-yl)pyrrolidin-1-yl)ethan-1-ol; 1-(7-(((R)-1-(2,4-dichlorophenyl)ethyl)amino)-2-(3-((R)-1-(2- 50 hydroxyethyl)piperidin-3-yl)azetidin-1-yl)benzo[d]oxazol-6-yl)-2,2,2- trifluoroethan-1-ol; 51 1-(7-(((R)-1-(2,4-dichlorophenyl)ethyl)amino)-2-(3-((R)-1-(2- hydroxyethyl)piperidin-3-yl)azetidin-1-yl)benzo[d]oxazol-6-yl)ethan-1-ol; and 52 2-((R)-3-(1-(7-(((R)-1-(2,4-dichlorophenyl)ethyl)amino)-6- (hydroxymethyl)benzo[d]oxazol-2-yl)azetidin-3-yl)piperidin-1-yl)ethan-1-ol; or a pharmaceutically acceptable salt thereof or a stereoisomer thereof.

20. A pharmaceutical composition comprising a compound according to any one of claims 1 to 19, or a pharmaceutically acceptable salt or a stereoisomer thereof and at least one pharmaceutically acceptable carrier or excipient.

21. The compound according to any one of claims 1 to 19 or a pharmaceutical acceptable salt or a stereoisomer thereof, for use as a medicament.

22. The compound according to any one of claims 1 to 19, or a pharmaceutical acceptable salt or a stereoisomer thereof, for use in the treatment of CCR4 mediated disease or disorder.

23. A method of modulating CCR4 in a subject, comprising administering to the subject a therapeutically effective amount of a compound according to any one of claims 1 to 19, or a pharmaceutically acceptable salt thereof.

24. A method of treating or preventing a disease or disorder mediated by CCR4 in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of a compound according to any one of claims 1 to 19, or a pharmaceutically acceptable salt thereof.

25. The method according to claim 24, wherein the disease or disorder is cancer or an inflammatory disease or disorder.

26. The method according to claim 24, wherein the disease or disorder is inflammation.

27. The method according to claim 25, wherein the inflammatory disease or disorder is dermatitis.

28. The method according to claim 27, wherein the disease or disorder is atopic dermatitis or contact dermatitis.

29. The method according to claim 24, wherein the disease or disorder is cancer.

30. The method according to claim 29, wherein the cancer is colon cancer, pancreatic cancer, intestinal cancer, breast cancer, lung cancer, gastric cancer, liver cancer or colorectal cancer.

31. The method according to any one of the claims 24 to 30, further comprising administering to the subject in need thereof one or more chemotherapeutic agents or anti- inflammatory agents.

32. A method of treating or preventing an inflammatory disease or disorder in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of a compound according to any one of claims 1 to 19, or a pharmaceutically acceptable salt thereof.

33. The method according to claim 32, wherein the inflammatory disease or disorder is inflammation.

34. The method according to claim 32, wherein the inflammatory disease or disorder is dermatitis.

35. The method according to claim 32, wherein the inflammatory disease or disorder is atopic dermatitis or contact dermatitis.

36. A method of treating or preventing cancer in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of a compound according to any one of claims 1 to 19, or a pharmaceutically acceptable salt thereof.

37. The method according to claim 36, wherein the cancer is colon cancer, pancreatic cancer, intestinal cancer, breast cancer, lung cancer, gastric cancer, liver cancer or colorectal cancer.

38. Use of a compound according to any one of claims 1 to 19, or a pharmaceutical acceptable salt or a stereoisomer thereof, in the manufacture of a medicament for the treatment of CCR4-mediated disease or disorder.

39. Use of a compound according to any one of claims 1 to 19, or a pharmaceutical acceptable salt or a stereoisomer thereof, in the manufacture of a medicament for the treatment of cancer or an inflammatory disease or disorder.

40. The use according to claim 39, wherein the inflammatory disease or disorder is dermatitis.

41. The use according to claim 39, wherein the inflammatory disease or disorder is atopic dermatitis or contact dermatitis.

42. The use according to claim 39, wherein the cancer is colon cancer, pancreatic cancer, intestinal cancer, breast cancer, lung cancer, gastric cancer, liver cancer or colorectal cancer.