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NO976158L - Azetidinone derivatives for the treatment of atherosclerosis - Google Patents

Azetidinone derivatives for the treatment of atherosclerosis

Info

Publication number
NO976158L
NO976158L NO976158A NO976158A NO976158L NO 976158 L NO976158 L NO 976158L NO 976158 A NO976158 A NO 976158A NO 976158 A NO976158 A NO 976158A NO 976158 L NO976158 L NO 976158L
Authority
NO
Norway
Prior art keywords
alkyl
aryl
atherosclerosis
treatment
heteroarylc
Prior art date
Application number
NO976158A
Other languages
Norwegian (no)
Other versions
NO976158D0 (en
Inventor
Dashyant Dhanak
Deirdre Mary Bernadette Hickey
Robert John Ife
Colin Andrew Leach
David Graham Tew
Original Assignee
Smithkline Beecham Plc
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority claimed from GBGB9513442.5A external-priority patent/GB9513442D0/en
Priority claimed from GBGB9515056.1A external-priority patent/GB9515056D0/en
Priority claimed from GBGB9515206.2A external-priority patent/GB9515206D0/en
Priority claimed from GBGB9516985.0A external-priority patent/GB9516985D0/en
Priority claimed from GBGB9525132.8A external-priority patent/GB9525132D0/en
Priority claimed from GBGB9608651.7A external-priority patent/GB9608651D0/en
Priority claimed from GBGB9608650.9A external-priority patent/GB9608650D0/en
Application filed by Smithkline Beecham Plc filed Critical Smithkline Beecham Plc
Publication of NO976158D0 publication Critical patent/NO976158D0/en
Publication of NO976158L publication Critical patent/NO976158L/en

Links

Classifications

    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D205/00Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom
    • C07D205/02Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings
    • C07D205/06Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
    • C07D205/08Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with one oxygen atom directly attached in position 2, e.g. beta-lactams
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D401/00Heterocyclic 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
    • C07D401/02Heterocyclic 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
    • C07D401/12Heterocyclic 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 chain containing hetero atoms as chain links
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00Drugs for disorders of the cardiovascular system
    • A61P9/10Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D205/00Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom
    • C07D205/02Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings
    • C07D205/06Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
    • C07D205/08Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with one oxygen atom directly attached in position 2, e.g. beta-lactams
    • C07D205/085Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with one oxygen atom directly attached in position 2, e.g. beta-lactams with a nitrogen atom directly attached in position 3
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D205/00Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom
    • C07D205/02Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings
    • C07D205/06Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
    • C07D205/08Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with one oxygen atom directly attached in position 2, e.g. beta-lactams
    • C07D205/09Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with one oxygen atom directly attached in position 2, e.g. beta-lactams with a sulfur atom directly attached in position 4
    • C07D205/095Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with one oxygen atom directly attached in position 2, e.g. beta-lactams with a sulfur atom directly attached in position 4 and with a nitrogen atom directly attached in position 3
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D405/00Heterocyclic 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
    • C07D405/02Heterocyclic 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
    • C07D405/12Heterocyclic 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
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D409/00Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
    • C07D409/02Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
    • C07D409/12Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D417/00Heterocyclic 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
    • C07D417/02Heterocyclic 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
    • C07D417/12Heterocyclic 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 chain containing hetero atoms as chain links

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Urology & Nephrology (AREA)
  • Vascular Medicine (AREA)
  • Cardiology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)

Abstract

Azetidinonforbindelser med formel (I) _» Z-R1 XCR4R$¿X¿Y hvori R1 og R2, som er like eller forskjellige, hver er valgt fra hydrogen, halogen, eller C(i^alkyl; R4 og R5, som er like eller forskjellige, hver er valgt fra hydrogen, C^alkyl, C(2-6)alkenyl, aryl, arylC^alkyl og heteroarylC^jalkyl som hver eventuelt er substituert, eller R4 og R5 kan være knyttet sammen til å danne resten av en cykloalkylring; X er en linkergruppe; Y er en eventuelt substituert arylgruppe; Z er oksygen og R3 er C(i.8)alkyl, C^cykloalkyl, heteroaryl, heteroarylC^alkyl, aryl eller arylC^alkyl, idet hver av disse eventuelt er substituert; eller Z er S(O)n hvori n er O, 1 eller 2 og R3 , Cp-ejcykloalkyl, C(3-8)CykloalkylC(i^)alkyl, aryl, arylCji^alkyl, heteroaryl eller heteroarylCfi^jalkyl, idet hver av disse eventuelt er substituert, forbindelsene er inhibitorer av enzymet Lp-PLA2 og er nyttige i terapien, særlig ved behandling av atherosklerose.Azetidinone Compounds of Formula (I) - Z-R1 XCR4R $ ¿X¿Y wherein R 1 and R 2, which are the same or different, are each selected from hydrogen, halogen, or C (C 1-6 alkyl; R 4 and R 5, which are the same or different, each selected from hydrogen, C 1-6 alkyl, C 2-6 alkenyl, aryl, arylC 1-6 alkyl and heteroarylC 1-4 alkyl each optionally substituted, or R 4 and R 5 may be linked to form the remainder of a cycloalkyl ring; X is a linker group; Y is an optionally substituted aryl group; Z is oxygen and R 3 is C 1 -C 8 alkyl, C 1-4 cycloalkyl, heteroaryl, heteroarylC 1-4 alkyl, aryl or arylC 1-4 alkyl, each of which is optionally or Z is S (O) n wherein n is O, 1 or 2 and R 3, C 1-8 cycloalkyl, C (3-8) CycloalkylC (1-) alkyl, aryl, arylC 1-4 alkyl, heteroaryl or heteroarylC 1-6 alkyl, each of which is optionally substituted, the compounds are inhibitors of the enzyme Lp-PLA2 and are useful in the therapy, especially in the treatment of atherosclerosis.

NO976158A 1995-07-01 1997-12-30 Azetidinone derivatives for the treatment of atherosclerosis NO976158L (en)

Applications Claiming Priority (8)

Application Number Priority Date Filing Date Title
GBGB9513442.5A GB9513442D0 (en) 1995-07-01 1995-07-01 Novel compounds
GBGB9515056.1A GB9515056D0 (en) 1995-07-22 1995-07-22 Novel compounds
GBGB9515206.2A GB9515206D0 (en) 1995-07-25 1995-07-25 Novel compounds
GBGB9516985.0A GB9516985D0 (en) 1995-08-18 1995-08-18 Novel compounds
GBGB9525132.8A GB9525132D0 (en) 1995-12-08 1995-12-08 Novel compounds
GBGB9608651.7A GB9608651D0 (en) 1996-04-26 1996-04-26 Novel compounds
GBGB9608650.9A GB9608650D0 (en) 1996-04-26 1996-04-26 Novel compounds
PCT/EP1996/002765 WO1997002242A1 (en) 1995-07-01 1996-06-20 Azetidinone derivatives for the treatment of atherosclerosis

Publications (2)

Publication Number Publication Date
NO976158D0 NO976158D0 (en) 1997-12-30
NO976158L true NO976158L (en) 1998-02-25

Family

ID=27562921

Family Applications (1)

Application Number Title Priority Date Filing Date
NO976158A NO976158L (en) 1995-07-01 1997-12-30 Azetidinone derivatives for the treatment of atherosclerosis

Country Status (23)

Country Link
EP (1) EP0840725A1 (en)
JP (1) JP2002515852A (en)
KR (1) KR19990028630A (en)
CN (1) CN1197452A (en)
AP (1) AP728A (en)
AU (1) AU708032B2 (en)
BG (1) BG102214A (en)
BR (1) BR9609445A (en)
CA (1) CA2225627A1 (en)
CZ (1) CZ422197A3 (en)
EA (1) EA199800109A1 (en)
HU (1) HUP9901153A3 (en)
IL (1) IL122650A0 (en)
MA (1) MA23922A1 (en)
MX (1) MX9800186A (en)
NO (1) NO976158L (en)
NZ (1) NZ311684A (en)
OA (1) OA10648A (en)
PE (1) PE8998A1 (en)
PL (1) PL324240A1 (en)
SK (1) SK178497A3 (en)
TR (1) TR199701762T1 (en)
WO (1) WO1997002242A1 (en)

Families Citing this family (20)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0869943A1 (en) * 1995-12-08 1998-10-14 Smithkline Beecham Plc Monocyclic beta-lactame derivatives for treatment of atherosclerosis
IL126696A0 (en) * 1996-04-26 1999-08-17 Smithkline Beecham Plc Azetidinone derivatives for the treatment of atherosclerosis
GB9608649D0 (en) * 1996-04-26 1996-07-03 Smithkline Beecham Plc Novel compounds
ATE437862T1 (en) 2000-02-16 2009-08-15 Smithkline Beecham Plc PYRIMIDINE-5-ONE DERIVATIVES AS LDL-PLA2 INHIBITORS
GB0024808D0 (en) 2000-10-10 2000-11-22 Smithkline Beecham Plc Novel compounds
US8962633B2 (en) 2007-05-11 2015-02-24 Thomas Jefferson University Methods of treatment and prevention of metabolic bone diseases and disorders
WO2008140449A1 (en) 2007-05-11 2008-11-20 Thomas Jefferson University Methods of treatment and prevention of neurodegenerative diseases and disorders
EP2155225B1 (en) 2007-05-11 2015-07-08 The Trustees of the University of Pennsylvania Methods of treatment of skin ulcers
UY33766A (en) 2010-12-06 2012-06-29 Glaxo Group Ltd COMPOUNDS WITH PYRIMIDINONE STRUCTURE FOR USE IN THE TREATMENT OF DISEASES MEDIATED BY Lp-PLA2
WO2012080497A2 (en) 2010-12-17 2012-06-21 Glaxo Group Limited Methods of treatment and prevention of eye diseases
US20140171431A1 (en) 2011-06-27 2014-06-19 Jianhua Shen Azole heterocyclic compound, preparation method, pharmaceutical composition and use
TW201321382A (en) 2011-07-27 2013-06-01 Glaxo Group Ltd Compounds
WO2013013503A1 (en) 2011-07-27 2013-01-31 Glaxo Group Limited 2,3-dihydroimidazo[1,2-c] pyrimidin-5(1h)-one compounds use as lp-pla2 inhibitors
PE20151251A1 (en) 2013-01-25 2015-09-10 Glaxosmithkline Ip Dev Ltd DERIVATIVES [5,6] IMIDAZO PYRIMIDONE BICYCLIC WITH ACTIVITY ON LP-PLA2 ENZYMES
AU2014210259B2 (en) 2013-01-25 2016-11-03 Glaxosmithkline Intellectual Property Development Limited Compounds
WO2014114249A1 (en) 2013-01-25 2014-07-31 Glaxosmithkline Intellectual Property Development Limited Bicyclic pyrimidone compounds as inhibitors of lp-pla2
WO2016012917A1 (en) 2014-07-22 2016-01-28 Glaxosmithkline Intellectual Property Development Limited 1,2,3,5-tetrahydroimidazo[1,2-c]pyrimidine derivatives useful in the treatment of diseases and disorders mediated by lp-pla2
WO2016012916A1 (en) 2014-07-22 2016-01-28 Glaxosmithkline Intellectual Property Development Limited 1,2,3,5-tetrahydroimidazo[1,2-c]pyrimidine derivatives useful in the treatment of diseases and disorders mediated by lp-pla2
EP4056571A4 (en) 2019-11-09 2024-01-24 Shanghai Simr Biotechnology Co., Ltd. Tricyclic dihydroimidazopyrimidone derivative, preparation method therefor, pharmaceutical composition and use thereof
CN115304620A (en) 2021-05-07 2022-11-08 上海赛默罗生物科技有限公司 Pyrimidone derivatives, preparation method, pharmaceutical composition and application thereof

Family Cites Families (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4680391A (en) * 1983-12-01 1987-07-14 Merck & Co., Inc. Substituted azetidinones as anti-inflammatory and antidegenerative agents
IL89835A0 (en) * 1988-04-11 1989-12-15 Merck & Co Inc Substituted azetidinones,their preparation and pharmaceutical compositions containing them
IL99658A0 (en) * 1990-10-15 1992-08-18 Merck & Co Inc Substituted azetidinones and pharmaceutical compositions containing them
GB9421816D0 (en) * 1994-10-29 1994-12-14 Smithkline Beecham Plc Novel compounds
MA23834A1 (en) * 1994-12-22 1996-10-01 Smithkline Beecham Plc PROCESS FOR THE PREPARATION OF INHIBITOR COMPOUNDS OF THE LP-PLA2 ENZYME AND PHARMACEUTICAL COMPOSITIONS CONTAINING THEM

Also Published As

Publication number Publication date
EA199800109A1 (en) 1998-10-29
AP9701161A0 (en) 1998-01-31
CN1197452A (en) 1998-10-28
PL324240A1 (en) 1998-05-11
BG102214A (en) 1998-08-31
WO1997002242A1 (en) 1997-01-23
AU708032B2 (en) 1999-07-29
JP2002515852A (en) 2002-05-28
AU6305096A (en) 1997-02-05
NO976158D0 (en) 1997-12-30
HUP9901153A2 (en) 1999-08-30
NZ311684A (en) 2000-04-28
OA10648A (en) 2002-09-25
SK178497A3 (en) 1998-07-08
IL122650A0 (en) 1998-08-16
MA23922A1 (en) 1996-12-31
PE8998A1 (en) 1998-03-20
CZ422197A3 (en) 1998-06-17
TR199701762T1 (en) 1998-05-21
KR19990028630A (en) 1999-04-15
BR9609445A (en) 1999-04-06
AP728A (en) 1999-01-29
CA2225627A1 (en) 1997-01-23
HUP9901153A3 (en) 1999-11-29
MX9800186A (en) 1998-07-31
EP0840725A1 (en) 1998-05-13

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