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BG102214A - Derivatives of azetidinons for the treatment of atherosclerosis - Google Patents

Derivatives of azetidinons for the treatment of atherosclerosis

Info

Publication number
BG102214A
BG102214A BG102214A BG10221498A BG102214A BG 102214 A BG102214 A BG 102214A BG 102214 A BG102214 A BG 102214A BG 10221498 A BG10221498 A BG 10221498A BG 102214 A BG102214 A BG 102214A
Authority
BG
Bulgaria
Prior art keywords
alkyl
optionally
aryl
value
whichcan
Prior art date
Application number
BG102214A
Other languages
Bulgarian (bg)
Inventor
Dashyant Dhanak
Deirdre HICKEY
Robert IFE
Colin LEACH
David TEW
Original Assignee
Smithkline Beecham P.L.C.
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 P.L.C. filed Critical Smithkline Beecham P.L.C.
Publication of BG102214A publication Critical patent/BG102214A/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

The azetidinon compounds are inhibitors of the LpPLA2 enzymeand can find application for the treatment of atherosclerosis.They have the formulawhere R1 & R2 which can be the same or different, are selectedseparately from hydrogen, halogen or C(1-8) alkyl; R4 & R5 whichcan be the same or different, are selected separately fromhydrogen, C(1-6)alkyl, C(2-6) alkenyl, aryl, aryl C(1-4)alkyl andheteroaryl C(1-4)alkyl, each of which can optionally besubstituted, or R4 & R5 can be bound together forming theremaining part of C(3-7) gycloalkyl ring; X is direct bond; thegroup X1(CH2)m where X1 is CO, CONR6, COO, CONR6CO or CONR60,where R6 is hydrogen or (C1-C6) alkyl and m has the value of 0 oris multiple having the value of from 1 to 12; the group (X1)aX2,where a has the value of 0 or 1, and X2 is C(1-12) alkylene chain,broken and/or discontinued in neighbourhood with Y by one or moreX3 groups selected from 0, S(0)x, NR6, alkene or alkyn group,where x has the value of 0, 1 or 2 or the C(1-12) alkylene chain,optionally discontinued by X1; Y is optionally substituted arylgroup; Z is oxygen, and R3 is C(1-8) alkyl, C(3-8) cycloalkyl,C(3-8) cyclo-alkyl C(1-6) alkyl, heteroalkyl,heteroalkyl-C(1-4)alkyl, aryl or aryl C(1-4)alkyl, each of whichcan optionally be substituted, or Z is S(0)n where n has the valueof 0, 1 or 2, and R3 is heteroaryl or heteroaryl C(1-4)alkyl, eachof which can optionally be substututed.22 claims
BG102214A 1995-07-01 1998-01-28 Derivatives of azetidinons for the treatment of atherosclerosis BG102214A (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 (1)

Publication Number Publication Date
BG102214A true BG102214A (en) 1998-08-31

Family

ID=27562921

Family Applications (1)

Application Number Title Priority Date Filing Date
BG102214A BG102214A (en) 1995-07-01 1998-01-28 Derivatives of azetidinons 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
WO1997021675A1 (en) * 1995-12-08 1997-06-19 Smithkline Beecham Plc Monocyclic beta-lactame derivatives for treatment of atherosclerosis
AU2698697A (en) * 1996-04-26 1997-11-19 Smithkline Beecham Plc Azetidinone derivatives for the treatment of atherosclerosis
GB9608649D0 (en) * 1996-04-26 1996-07-03 Smithkline Beecham Plc Novel compounds
PT1686119E (en) 2000-02-16 2009-10-06 Smithkline Beecham Plc Pyrimidine-5-one derivatives as ldl-pla2 inhibitors
GB0024808D0 (en) 2000-10-10 2000-11-22 Smithkline Beecham Plc Novel compounds
MX2009012197A (en) 2007-05-11 2010-01-15 Univ Pennsylvania Methods of treatment of skin ulcers.
MX2009012188A (en) 2007-05-11 2010-02-24 Univ Jefferson Methods of treatment and prevention of neurodegenerative diseases and disorders.
US8962633B2 (en) 2007-05-11 2015-02-24 Thomas Jefferson University Methods of treatment and prevention of metabolic bone diseases and disorders
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
EP2651403B1 (en) 2010-12-17 2020-12-02 Glaxo Group Limited Use of lp-pla2 inhibitors in the 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
EP2739627A4 (en) 2011-07-27 2015-01-21 Glaxo Group Ltd 2,3-dihydroimidazo[1,2-c]pyrimidin-5(1h)-one compounds use as lp-pla² inhibitors
UY34216A (en) 2011-07-27 2013-02-28 Glaxo Group Ltd New compounds that inhibit the activity of Lp-PLA2
WO2014114248A1 (en) 2013-01-25 2014-07-31 Glaxosmithkline Intellectual Property Development Limited Compounds
KR20150108897A (en) 2013-01-25 2015-09-30 글락소스미스클라인 인털렉츄얼 프로퍼티 디벨로프먼트 리미티드 2,3-dihydroimidazol[1,2-c]pyrimidin-5(1h)-one based lipoprotein-associated phospholipase a2 (lp-pla2) inhibitors
AU2014210260B2 (en) 2013-01-25 2016-08-04 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
NZ228600A (en) * 1988-04-11 1992-02-25 Merck & Co Inc 1-(benzylaminocarbonyl)-4-phenoxy-azetidin-2-one derivatives
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
AP9701007A0 (en) * 1994-12-22 1997-07-31 Smithkline Beecham Plc Substituted azetidin-2-ones for treatment of atherosclerosis.

Also Published As

Publication number Publication date
BR9609445A (en) 1999-04-06
EA199800109A1 (en) 1998-10-29
WO1997002242A1 (en) 1997-01-23
CZ422197A3 (en) 1998-06-17
SK178497A3 (en) 1998-07-08
NO976158L (en) 1998-02-25
KR19990028630A (en) 1999-04-15
IL122650A0 (en) 1998-08-16
PL324240A1 (en) 1998-05-11
NZ311684A (en) 2000-04-28
JP2002515852A (en) 2002-05-28
HUP9901153A3 (en) 1999-11-29
NO976158D0 (en) 1997-12-30
AU6305096A (en) 1997-02-05
PE8998A1 (en) 1998-03-20
AU708032B2 (en) 1999-07-29
EP0840725A1 (en) 1998-05-13
TR199701762T1 (en) 1998-05-21
MX9800186A (en) 1998-07-31
CA2225627A1 (en) 1997-01-23
HUP9901153A2 (en) 1999-08-30
OA10648A (en) 2002-09-25
AP728A (en) 1999-01-29
AP9701161A0 (en) 1998-01-31
MA23922A1 (en) 1996-12-31
CN1197452A (en) 1998-10-28

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