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RS54798B1 - Pozitivni alosterni modulatori m1 receptora na bazi hinolin amida - Google Patents

Pozitivni alosterni modulatori m1 receptora na bazi hinolin amida

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Publication number
RS54798B1
RS54798B1 RS20160369A RSP20160369A RS54798B1 RS 54798 B1 RS54798 B1 RS 54798B1 RS 20160369 A RS20160369 A RS 20160369A RS P20160369 A RSP20160369 A RS P20160369A RS 54798 B1 RS54798 B1 RS 54798B1
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RS
Serbia
Prior art keywords
alkyl
group
ring
ring atoms
hydroxyl
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RS20160369A
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English (en)
Inventor
Scott D Kuduk
Kelly-Ann Schlegel
Zhi-Qiang Yang
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Merck Sharp & Dohme
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Publication date
Application filed by Merck Sharp & Dohme filed Critical Merck Sharp & Dohme
Publication of RS54798B1 publication Critical patent/RS54798B1/sr

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    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
    • C07D215/58—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems with hetero atoms directly attached to the ring nitrogen atom
    • C07D215/60—N-oxides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/47—Quinolines; Isoquinolines
    • A61K31/4704—2-Quinolinones, e.g. carbostyril
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/47—Quinolines; Isoquinolines
    • A61K31/472—Non-condensed isoquinolines, e.g. papaverine
    • A61K31/4725—Non-condensed isoquinolines, e.g. papaverine containing further heterocyclic rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
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    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/04—Centrally acting analgesics, e.g. opioids
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    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/20—Hypnotics; Sedatives
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • C—CHEMISTRY; METALLURGY
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    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
    • C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
    • C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D215/48—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
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    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
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    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
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    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/10—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing aromatic rings
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    • C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
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    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
    • C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
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    • C07—ORGANIC CHEMISTRY
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    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
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    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
    • C07D409/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
    • C07D413/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
    • C07D413/10—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing aromatic rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
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    • C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
    • C07D417/10—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a carbon chain containing aromatic rings
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    • C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings
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    • C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
    • C07D471/04—Ortho-condensed systems

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  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
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  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Biomedical Technology (AREA)
  • Neurology (AREA)
  • Neurosurgery (AREA)
  • Epidemiology (AREA)
  • Psychiatry (AREA)
  • Pain & Pain Management (AREA)
  • Anesthesiology (AREA)
  • Rheumatology (AREA)
  • Hospice & Palliative Care (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Quinoline Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)

Abstract

Jedinjenje formule (I):u komeX1 je izabran iz grupe koja se sastoji od(1) N, i(2) N→O;X2-X3 je izabran iz grupe koja se sastoji od(1)-CH2-CH2-,(2)-O-CH2-,(3)-CH2-O-, ili(4)-CH2-;X4, X5, X6 i X7 su svaki izabran iz grupe koja se sastoji od(1) N,(2) N→O,(3) CH,(4) Ouz uslov da jedan od X4, X5, X6 i X7 može biti odsutan, na taj način formirajući peto-člani prsten;R1 je izabran iz grupe koja se sastoji od(1) vodonika,(2) halogena,(3) -C,.6 alkil,(4) -C2-6 alkinil,(4) fenil,(5) =O,(6) =CH2,(7) hidroksil,gde je R1 alkil, alkinil ili fenil grapa izbomo supstituisana sajednim ili više(a) hidroksil, ili(b) halogen;R2A i R2B su nezavisno izabrani iz grupe koja se sastoji od(1) vodonika,(2) hidroksil i(3) halogena,ili R2A i R2B zajedno formiraju =O;R3 je izborno prisutan na jednom ili više atoma ugljenika u prstenu, i nezavisno je izabran iz grupe koja se sastoji od(1) halogena,(2) -O-C1-6alkil,(3) -S-C1-6 alkil, ili(4) heteroaril grupe, koja je aromatična ciklična grupa, koja ima od pet do dvanaest atoma u prstenu, pri čemu su navedeni atomi prstena izabrani od C, O, N, N→O ili S, od kojih je najmanje jedan O, N, N→O ili S, pri čemu je heteroaril izborno supstituisan sa C1-6 alkil;R4 je izborno prisutan na jednom ili više atoma u prstenu, i izabran je iz grupe koja se sastoji od(1) hidroksil,(2) halogena,(3) -C1-6 alkil,(4) -O-C1-6 alkil,(5) -S-C1-6 alkil,(6) -C3-8 cikloalkil,(7) -C6-10 aril,(8) -CN,(9) heteroaril grupe, koja je aromatična ciklična grupa, koja ima od pet do dvanaest atoma u prstenu, pri čemu su navedeni atomi prstena izabrani od C, O, N, N→O ili S, od kojih je najmanje jedan O, N, N→O ili S,(10) -O-heterociklil,(11) -NRARB,gde su RA i RB izabrani iz grupe koja se sastoji od(a) vodonika ili(b) –C1-6alkil,ili RA i RB su povezani zajedno sa azotom za koji su vezani tako da formiraju 4-6 -člani karbocikličan prsten, pri čemu su jedan ili dva od atoma ugljenika u prstenu izborno zamenjeni azotom, kiseonikom ili sumporom, i prsten je izborno supstituisan sa jednim ili više(a) halogena,(b) hidroksil,(c) C1-6 alkil,(d) -O-C1-6 alkil,(e) -C(=O)-(O)n -C1-6 alkil;gde n je 0-1; i alkil, cikloalkil, aril ili heteroaril R4 grupa je izborno supstituisana sa jednim iliviše(a) halogena,(b) hidroksi,(c) -O- C1-6 alkil,(d) - C1-6 alkil,(e) -S-C1-6 alkil, ili(f) heteroaril grupe, koja je aromatična ciklična grupa, koja ima od pet do dvanaest atoma u prstenu, pri čemu su navedeni atomi prstena izabrani od C, O, N, N→ O ili S, od kojih je najmanje jedan O, N, N→O ili S,gde je alkil, aril ili heteroaril grupa izborno supstituisana sa jednim ili više(i) halogena,(ii) hidroksi,(iii) -O-C1-6 alkil, ili(iv) -C1-6 alkil;ili dve R4 grupe su povezane zajedno tako da formiraju fuzionisanu prstenastu heteroaril grupu sa tri ili četiri atoma, pri čemu su navedeni atomi prstena izabrani od C, O, N, N→O ili S, od kojih je najmanje jedan O, N, N→O ili S, ili njegova farmaceutski prihvatljiva so.Prijava sadrži još 21 patentni zahtev.
RS20160369A 2009-12-17 2010-12-13 Pozitivni alosterni modulatori m1 receptora na bazi hinolin amida RS54798B1 (sr)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US28753509P 2009-12-17 2009-12-17
EP10841821.1A EP2512243B1 (en) 2009-12-17 2010-12-13 Quinoline amide m1 receptor positive allosteric modulators
PCT/US2010/060007 WO2011084368A1 (en) 2009-12-17 2010-12-13 Quinoline amide m1 receptor positive allosteric modulators

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RS54798B1 true RS54798B1 (sr) 2016-10-31

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EP (1) EP2512243B1 (sr)
JP (1) JP5651708B2 (sr)
KR (1) KR101494059B1 (sr)
CN (1) CN102651970B (sr)
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