CA2225627A1 - Derives de l'azetidinone pour le traitement de l'atherosclerose - Google Patents

Derives de l'azetidinone pour le traitement de l'atherosclerose Download PDF

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Publication number
CA2225627A1
CA2225627A1 CA002225627A CA2225627A CA2225627A1 CA 2225627 A1 CA2225627 A1 CA 2225627A1 CA 002225627 A CA002225627 A CA 002225627A CA 2225627 A CA2225627 A CA 2225627A CA 2225627 A1 CA2225627 A1 CA 2225627A1
Authority
CA
Canada
Prior art keywords
oxoazetidin
diastereoisomer
benzylsulphinyl
acetamide
hexyl
Prior art date
Legal status (The legal status 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 status listed.)
Abandoned
Application number
CA002225627A
Other languages
English (en)
Inventor
Deirdre Mary Bernadette Hickey
Robert John Ife
Dashyant Dhanak
David Graham Tew
Colin Andrew Leach
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
SmithKline Beecham Ltd
Original Assignee
Individual
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 Individual filed Critical Individual
Publication of CA2225627A1 publication Critical patent/CA2225627A1/fr
Abandoned legal-status Critical Current

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D205/00—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom
    • C07D205/02—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings
    • C07D205/06—Heterocyclic 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
    • C07D205/08—Heterocyclic 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • 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
    • C07D401/12—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 chain containing hetero atoms as chain links
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/10—Drugs 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D205/00—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom
    • C07D205/02—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings
    • C07D205/06—Heterocyclic 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
    • C07D205/08—Heterocyclic 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
    • C07D205/085—Heterocyclic 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D205/00—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom
    • C07D205/02—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings
    • C07D205/06—Heterocyclic 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
    • C07D205/08—Heterocyclic 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
    • C07D205/09—Heterocyclic 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
    • C07D205/095—Heterocyclic 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
    • C—CHEMISTRY; METALLURGY
    • 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
    • C—CHEMISTRY; METALLURGY
    • 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
    • C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
    • C07D409/12—Heterocyclic 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—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
    • 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
    • C07D417/12—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 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

L'invention concerne les composés de l'azétidinone présentant la formule (I). Dans cette formule, R?1¿ et R?2¿ peuvent être identiques ou différents, et sont chacun sélectionnés parmi de l'hydrogène, de l'halogène ou de l'alkyle (C¿1-8?); R?4¿ et R?5¿ peuvent être semblables ou différents et sont chacun sélectionnés parmi de l'hydrogène, de l'alkyle (C¿1-6?), de l'alcényle (C¿2-6?), de l'aryle, de l'arylalkyle (C¿1-4?) et de l'hétéroarylalkyle (C¿1-4?), qui peuvent être tous éventuellement substitués, ou R?4¿ et R?5¿ peuvent être liés ensemble pour former le reste d'un noyau de cycloalkyle (C¿3-7?); X est un groupe de liaison; Y est un groupe aryle éventuellement substitué; Z est de l'oxygène et R?3¿ est de l'alkyle (C¿1-8?), du cycloalkyle (C¿3-8?), du cycloalkyle(C¿3-8?)alkyle(C¿1-6?), de l'hétéroaryle, de l'hétéroarylalkyle (C¿1-4?), de l'aryle, ou de l'arylalkyle (C¿1-4?) qui peuvent être tous éventuellement substitués, ou Z désigne à S(O)n où n vaut 0, 1 ou 2 et R?3¿ est de l'alkyle (C¿1-8?), du cycloalkyle (C¿3-8?), du cycloalkyle (C¿3-8?), de l'aryle, de l'alkyle (C¿1-4?) d'aryle, de l'hétéroaryle, ou de l' hétéroarylalkyle (C¿1-4?), qui peuvent tous être éventuellement substitués. Ces composés sont des inhibiteurs de l'enzyme Lp PLA2 et sont particulièrement utiles dans le traitement de l'athérosclérose.
CA002225627A 1995-07-01 1996-06-20 Derives de l'azetidinone pour le traitement de l'atherosclerose Abandoned CA2225627A1 (fr)

Applications Claiming Priority (14)

Application Number Priority Date Filing Date Title
GB9513442.5 1995-07-01
GBGB9513442.5A GB9513442D0 (en) 1995-07-01 1995-07-01 Novel compounds
GB9515056.1 1995-07-22
GBGB9515056.1A GB9515056D0 (en) 1995-07-22 1995-07-22 Novel compounds
GBGB9515206.2A GB9515206D0 (en) 1995-07-25 1995-07-25 Novel compounds
GB9515206.2 1995-07-25
GB9516985.0 1995-08-18
GBGB9516985.0A GB9516985D0 (en) 1995-08-18 1995-08-18 Novel compounds
GBGB9525132.8A GB9525132D0 (en) 1995-12-08 1995-12-08 Novel compounds
GB9525132.8 1995-12-08
GB9608650.9 1996-04-26
GBGB9608651.7A GB9608651D0 (en) 1996-04-26 1996-04-26 Novel compounds
GB9608651.7 1996-04-26
GBGB9608650.9A GB9608650D0 (en) 1996-04-26 1996-04-26 Novel compounds

Publications (1)

Publication Number Publication Date
CA2225627A1 true CA2225627A1 (fr) 1997-01-23

Family

ID=27562921

Family Applications (1)

Application Number Title Priority Date Filing Date
CA002225627A Abandoned CA2225627A1 (fr) 1995-07-01 1996-06-20 Derives de l'azetidinone pour le traitement de l'atherosclerose

Country Status (23)

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

Families Citing this family (20)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0869943A1 (fr) * 1995-12-08 1998-10-14 Smithkline Beecham Plc Derives de beta-lactame monocycliques utilises dans le traitement de l'atherosclerose
GB9608649D0 (en) * 1996-04-26 1996-07-03 Smithkline Beecham Plc Novel compounds
BR9709196A (pt) * 1996-04-26 1999-05-25 Smithkline Beecham Plc Derivados de azetidinona para o tratamento de aterosclerose
EP1686119B1 (fr) 2000-02-16 2009-07-29 Smithkline Beecham Plc Dérivés de Pyrimidine-5-one comme inhibiteurs LDL-PLA2
GB0024808D0 (en) 2000-10-10 2000-11-22 Smithkline Beecham Plc Novel compounds
AU2008251467B2 (en) 2007-05-11 2014-07-31 The Trustees Of The University Of Pennsylvania Methods of treatment of skin ulcers
KR101690390B1 (ko) 2007-05-11 2016-12-27 토마스 제퍼슨 유니버시티 신경변성 질환 및 장애의 치료 및 예방 방법
US8962633B2 (en) 2007-05-11 2015-02-24 Thomas Jefferson University Methods of treatment and prevention of metabolic bone diseases and disorders
CA2820408C (fr) 2010-12-06 2018-03-06 Glaxo Group Limited Composes de pyrimidinone utiles dans le traitement de maladies ou d'etats pathologiques induits par la lp-pla2
EP2651403B1 (fr) 2010-12-17 2020-12-02 Glaxo Group Limited Procédés de traitement et de prévention de maladies oculaires
WO2013000267A1 (fr) 2011-06-27 2013-01-03 中国科学院上海药物研究所 Composé hétérocyclique azole, procédé de préparation, composition pharmaceutique et utilisation
KR20140059203A (ko) 2011-07-27 2014-05-15 글락소 그룹 리미티드 2,3-디히드로이미다조[1,2-c]피리미딘-5(1h)-온 화합물의 lp-pla2 억제제로서의 용도
EP2736908A1 (fr) 2011-07-27 2014-06-04 Glaxo Group Limited Composés pyrimidones bicycliques
KR20150111356A (ko) 2013-01-25 2015-10-05 글락소스미스클라인 인털렉츄얼 프로퍼티 디벨로프먼트 리미티드 화합물
MX2015009633A (es) 2013-01-25 2015-11-30 Glaxosmithkline Ip Dev Ltd Inhibidores de fosfolipasa a2 asociada con lipoproteinas basados en 2,3-dihidroimidazol[1,2-c] pirimidin-5(1h)-ona.
AU2014210260B2 (en) 2013-01-25 2016-08-04 Glaxosmithkline Intellectual Property Development Limited Bicyclic pyrimidone compounds as inhibitors of Lp-PLA2
WO2016012917A1 (fr) 2014-07-22 2016-01-28 Glaxosmithkline Intellectual Property Development Limited Dérivés 1,2,3,5-tétrahydro-imidazo [1,2-c]pyrimidine utiles pour le traitement de maladies et de troubles médiés par la lp-pla2
WO2016012916A1 (fr) 2014-07-22 2016-01-28 Glaxosmithkline Intellectual Property Development Limited Dérivés 1,2,3,5-tétrahydro-imidazo [1,2-c]pyrimidine utiles pour le traitement de maladies et de troubles médiés par la lp-pla2
JP2023500710A (ja) 2019-11-09 2023-01-10 シャンハイ エスアイエムアール バイオテクノロジー カンパニー リミテッド 三環式ジヒドロイミダゾピリミドン誘導体、その調製方法、その医薬組成物及び使用
CN115304620A (zh) 2021-05-07 2022-11-08 上海赛默罗生物科技有限公司 嘧啶酮衍生物、其制备方法、药物组合物和用途

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
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 (pt) 1999-04-06
AP728A (en) 1999-01-29
MA23922A1 (fr) 1996-12-31
WO1997002242A1 (fr) 1997-01-23
MX9800186A (es) 1998-07-31
CN1197452A (zh) 1998-10-28
EA199800109A1 (ru) 1998-10-29
HUP9901153A3 (en) 1999-11-29
HUP9901153A2 (hu) 1999-08-30
PE8998A1 (es) 1998-03-20
TR199701762T1 (xx) 1998-05-21
SK178497A3 (en) 1998-07-08
EP0840725A1 (fr) 1998-05-13
IL122650A0 (en) 1998-08-16
NZ311684A (en) 2000-04-28
CZ422197A3 (cs) 1998-06-17
AU6305096A (en) 1997-02-05
OA10648A (en) 2002-09-25
NO976158D0 (no) 1997-12-30
AP9701161A0 (en) 1998-01-31
NO976158L (no) 1998-02-25
BG102214A (en) 1998-08-31
PL324240A1 (en) 1998-05-11
JP2002515852A (ja) 2002-05-28
AU708032B2 (en) 1999-07-29
KR19990028630A (ko) 1999-04-15

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Legal Events

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FZDE Discontinued