NO976158L - Azetidinone derivatives for the treatment of atherosclerosis - Google Patents
Azetidinone derivatives for the treatment of atherosclerosisInfo
- 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
Links
- 201000001320 Atherosclerosis Diseases 0.000 title abstract 2
- MNFORVFSTILPAW-UHFFFAOYSA-N azetidin-2-one Chemical class O=C1CCN1 MNFORVFSTILPAW-UHFFFAOYSA-N 0.000 title abstract 2
- 125000000217 alkyl group Chemical group 0.000 abstract 10
- 125000003118 aryl group Chemical group 0.000 abstract 3
- 125000000753 cycloalkyl group Chemical group 0.000 abstract 3
- 125000001072 heteroaryl group Chemical group 0.000 abstract 2
- 229910052739 hydrogen Inorganic materials 0.000 abstract 2
- 239000001257 hydrogen Substances 0.000 abstract 2
- 150000002431 hydrogen Chemical class 0.000 abstract 2
- 102000016752 1-Alkyl-2-acetylglycerophosphocholine Esterase Human genes 0.000 abstract 1
- 108010024976 Asparaginase Proteins 0.000 abstract 1
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 abstract 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 abstract 1
- 150000001875 compounds Chemical class 0.000 abstract 1
- 229910052736 halogen Inorganic materials 0.000 abstract 1
- 150000002367 halogens Chemical class 0.000 abstract 1
- 239000003112 inhibitor Substances 0.000 abstract 1
- 125000005647 linker group Chemical group 0.000 abstract 1
- 229910052760 oxygen Inorganic materials 0.000 abstract 1
- 239000001301 oxygen Substances 0.000 abstract 1
- 125000003107 substituted aryl group Chemical group 0.000 abstract 1
- 238000002560 therapeutic procedure Methods 0.000 abstract 1
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
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.
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)
| 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)
| 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 |
-
1996
- 1996-06-20 TR TR97/01762T patent/TR199701762T1/en unknown
- 1996-06-20 CZ CZ974221A patent/CZ422197A3/en unknown
- 1996-06-20 EA EA199800109A patent/EA199800109A1/en unknown
- 1996-06-20 BR BR9609445A patent/BR9609445A/en unknown
- 1996-06-20 NZ NZ311684A patent/NZ311684A/en unknown
- 1996-06-20 AP APAP/P/1997/001161A patent/AP728A/en active
- 1996-06-20 CN CN96196661A patent/CN1197452A/en active Pending
- 1996-06-20 WO PCT/EP1996/002765 patent/WO1997002242A1/en not_active Ceased
- 1996-06-20 EP EP96922030A patent/EP0840725A1/en not_active Withdrawn
- 1996-06-20 IL IL12265096A patent/IL122650A0/en unknown
- 1996-06-20 AU AU63050/96A patent/AU708032B2/en not_active Ceased
- 1996-06-20 SK SK1784-97A patent/SK178497A3/en unknown
- 1996-06-20 KR KR1019970709952A patent/KR19990028630A/en not_active Withdrawn
- 1996-06-20 HU HU9901153A patent/HUP9901153A3/en unknown
- 1996-06-20 PL PL96324240A patent/PL324240A1/en unknown
- 1996-06-20 CA CA002225627A patent/CA2225627A1/en not_active Abandoned
- 1996-06-20 JP JP50477297A patent/JP2002515852A/en active Pending
- 1996-06-28 PE PE1996000496A patent/PE8998A1/en not_active Application Discontinuation
- 1996-06-28 MA MA24298A patent/MA23922A1/en unknown
-
1997
- 1997-12-30 NO NO976158A patent/NO976158L/en unknown
- 1997-12-31 OA OA70172A patent/OA10648A/en unknown
-
1998
- 1998-01-07 MX MX9800186A patent/MX9800186A/en unknown
- 1998-01-28 BG BG102214A patent/BG102214A/en unknown
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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