TR199701762T1 - Azetidinone derivatives for the treatment of atherosclerosis. - Google Patents

Azetidinone derivatives for the treatment of atherosclerosis.

Info

Publication number
TR199701762T1
TR199701762T1 TR97/01762T TR9701762T TR199701762T1 TR 199701762 T1 TR199701762 T1 TR 199701762T1 TR 97/01762 T TR97/01762 T TR 97/01762T TR 9701762 T TR9701762 T TR 9701762T TR 199701762 T1 TR199701762 T1 TR 199701762T1
Authority
TR
Turkey
Prior art keywords
alkyl
aryl
cycloalkyl
heteroaryl
optionally substituted
Prior art date
Application number
TR97/01762T
Other languages
Turkish (tr)
Inventor
Dhanak Dashyant
Mary Bernadette Hickey Deirdre
John Ife Robert
Andrew Leach Colin
Graham Tew David
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 GBGB9608650.9A external-priority patent/GB9608650D0/en
Priority claimed from GBGB9608651.7A external-priority patent/GB9608651D0/en
Application filed by Smithkline Beecham P.L.C. filed Critical Smithkline Beecham P.L.C.
Publication of TR199701762T1 publication Critical patent/TR199701762T1/en

Links

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

Abstract

Ayni veya farkli olabilen her bir R1 ve R2 nin hidrojen, halojen veya C(1-8) alkilden seçildigi; ayni veya farkli olabilen her bir R4 ve R5 in her birinin tercihe göre ikame edilebildigi hidrojen, C(1-6) alkil, C(2-6) alkenil, aril, aril (C1-4) alkil ve heteroaril (C1-4) alkilden seçildigi veya R4 ve R5 in bir (C3-7) sikloalkil halkasinin kalan kismini olusturmak üzere birlestirilebildigi; X'in bir baglayici grup oldugu; Y nin tercihe göre ikameli bir aril grubu oldugu; Z nin oksijen ve R3 ün, her biri tercihe göre ikame edilebilen C(1-8) alkil, C(3-8) sikloalkil, C(3-8) sikloalkil C(1-6) alkil, heteroaril, (C1-4) alkil, aril veya aril (C1-4) alkil oldugu veya Z'nin n'nin 0.1 veya 2 oldugu S(0)n oldugu, ve R3 ün her biri tercihe göre ikame edilebilen C(1-8) alkil, C(3-8) sikloalkil, C(3-8) sikloalkil C(1-6) alkil, aril, aril (C1-4) alkil heteroaril veya heteroaril (C1-4) alkil oldugu; formül (1) in azetidinon bilesimleri, LpPLA2 enziminin engelleyicileri olup; (DEVAMI VAR).Each R1 and R2, which may be the same or different, is selected from hydrogen, halogen or C (1-8) alkyl; hydrogen, C (1-6) alkyl, C (2-6) alkenyl, aryl, aryl (C1-4) alkyl and heteroaryl (C1-4) where each of R4 and R5, which may be the same or different, can be optionally substituted. is selected from alkyl or R4 and R5 can be combined to form the remaining portion of a (C3-7) cycloalkyl ring; X is a linking group; Y is an optionally substituted aryl group; Z is oxygen and R3 is C (1-8) alkyl, C (3-8) cycloalkyl, C (3-8) cycloalkyl C (1-6) alkyl, heteroaryl, (C1-4) each optionally substituted. ) is alkyl, aryl or aryl (C1-4) alkyl, or S (0) n where Z is 0.1 or 2, and R3 is C (1-8) alkyl, each of which may be optionally substituted. 3-8) cycloalkyl, C (3-8) cycloalkyl C (1-6) alkyl, aryl, aryl (C1-4) alkyl heteroaryl or heteroaryl (C1-4) alkyl; The azetidinone compounds of formula (1) are inhibitors of the LpPLA2 enzyme; (CONTINUE).

TR97/01762T 1995-07-01 1996-06-20 Azetidinone derivatives for the treatment of atherosclerosis. TR199701762T1 (en)

Applications Claiming Priority (7)

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
GBGB9608650.9A GB9608650D0 (en) 1996-04-26 1996-04-26 Novel compounds
GBGB9608651.7A GB9608651D0 (en) 1996-04-26 1996-04-26 Novel compounds

Publications (1)

Publication Number Publication Date
TR199701762T1 true TR199701762T1 (en) 1998-05-21

Family

ID=27562921

Family Applications (1)

Application Number Title Priority Date Filing Date
TR97/01762T TR199701762T1 (en) 1995-07-01 1996-06-20 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
JP2000502079A (en) * 1995-12-08 2000-02-22 スミスクライン・ビーチャム・パブリック・リミテッド・カンパニー Monocyclic .BETA.-lactam derivatives for the treatment of atherosclerosis
BR9709196A (en) * 1996-04-26 1999-05-25 Smithkline Beecham Plc Azetidinone derivatives for the treatment of atherosclerosis
GB9608649D0 (en) * 1996-04-26 1996-07-03 Smithkline Beecham Plc Novel compounds
WO2001060805A1 (en) 2000-02-16 2001-08-23 Smithkline Beecham P.L.C. Pyrimidine-4-one derivatives as ldl-pla2 inhibitors
GB0024808D0 (en) 2000-10-10 2000-11-22 Smithkline Beecham Plc Novel compounds
KR101461659B1 (en) 2007-05-11 2014-11-17 토마스 제퍼슨 유니버시티 Methods of treatment and prevention of neurodegenerative diseases and disorders
WO2008141176A1 (en) 2007-05-11 2008-11-20 The Trustees Of The University Of Pennsylvania Methods of treatment of skin ulcers
US8962633B2 (en) 2007-05-11 2015-02-24 Thomas Jefferson University Methods of treatment and prevention of metabolic bone diseases and disorders
JP5886310B2 (en) 2010-12-06 2016-03-16 グラクソ グループ リミテッドＧｌａｘｏ Ｇｒｏｕｐ Ｌｉｍｉｔｅｄ Pyrimidinone compounds for use in the treatment of diseases or conditions 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
CN103619831B (en) 2011-06-27 2016-05-04 中国科学院上海药物研究所 Azole heterocyclic compound, its preparation method, pharmaceutical composition and purposes
BR112014001665A2 (en) 2011-07-27 2017-02-14 Glaxo Group Ltd 2,3-dihydroimidazo [1,2-c] pyrimidin-5 (1h) -one compounds used as lp-plaz inhibitors
RU2014107486A (en) 2011-07-27 2015-09-10 Глэксо Груп Лимитед Bicyclic pyrimidone compounds
JP2016505053A (en) 2013-01-25 2016-02-18 グラクソスミスクライン、インテレクチュアル、プロパティー、ディベロップメント、リミテッドＧｌａｘｏｓｍｉｔｈｋｌｉｎｅ Ｉｎｔｅｌｌｅｃｔｕａｌ Ｐｒｏｐｅｒｔｙ Ｄｅｖｅｌｏｐｍｅｎｔ Ｌｉｍｉｔｅｄ Bicyclic pyrimidone compounds as inhibitors of Lp-PLA2
UY35276A (en) 2013-01-25 2014-08-29 Glaxosmithkline Ip Dev Ltd New compounds that inhibit the activity of Lp-PLA2
WO2014114248A1 (en) 2013-01-25 2014-07-31 Glaxosmithkline Intellectual Property Development Limited Compounds
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
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
CN112778331B (en) 2019-11-09 2022-07-05 上海赛默罗生物科技有限公司 Tricyclic dihydroimidazopyrimidinone derivatives, preparation method, pharmaceutical composition and application 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
PL320937A1 (en) * 1994-12-22 1997-11-10 Smithkline Beecham Plc Substituted azetidin-2-ones for treating arterial atheromatosis

Also Published As

Publication number Publication date
NO976158L (en) 1998-02-25
SK178497A3 (en) 1998-07-08
JP2002515852A (en) 2002-05-28
PL324240A1 (en) 1998-05-11
EP0840725A1 (en) 1998-05-13
WO1997002242A1 (en) 1997-01-23
BG102214A (en) 1998-08-31
CN1197452A (en) 1998-10-28
AU708032B2 (en) 1999-07-29
EA199800109A1 (en) 1998-10-29
HUP9901153A2 (en) 1999-08-30
AU6305096A (en) 1997-02-05
HUP9901153A3 (en) 1999-11-29
PE8998A1 (en) 1998-03-20
KR19990028630A (en) 1999-04-15
CA2225627A1 (en) 1997-01-23
NO976158D0 (en) 1997-12-30
CZ422197A3 (en) 1998-06-17
BR9609445A (en) 1999-04-06
IL122650A0 (en) 1998-08-16
MA23922A1 (en) 1996-12-31
AP9701161A0 (en) 1998-01-31
MX9800186A (en) 1998-07-31
OA10648A (en) 2002-09-25
AP728A (en) 1999-01-29
NZ311684A (en) 2000-04-28

Similar Documents

Publication Publication Date Title
TR199701762T1 (en) Azetidinone derivatives for the treatment of atherosclerosis.
NO982913L (en) Quinoline and quinazoline compounds useful in therapy
NO972909L (en) Substituted azetidin-2-ones for the treatment of atherosclerosis
EA199800664A1 (en) SUBSTITUTED DERIVATIVES OF 4-HYDROXY-PHENYLALCANIC ACID WITH AGONISTIC ACTIVITY WITH RESPECT TO PPAR-GAMMA
DE60139429D1 (en) Pyrimidine-5-onderivatives as LDL-PLA2 inhibitors
TR200000735T2 (en) Benzamidoxime derivative, intermediates and production methods.
DE69911980D1 (en) PYRIMIDINE DERIVATIVES FOR TREATING ATHEROSCLEROS
NO983529D0 (en) Dihydrobenzofuran and related compounds useful as anti-inflammatory agents
ATE37375T1 (en) PHOSPHONYL HYDROXYACYL AMINO ACID DERIVATIVES AND THEIR USE AS ANTIHYPERTENSIVES.
DE69821985D1 (en) ORTHO-ANTHRANILAMID DERIVATIVES AS ANTICOAGULANTIES
TR199700625T1 (en) Indole derivatives useful in the treatment of osteoporosis (bone loss).
HUP0000942A2 (en) Quinoline and quinazoline compounds pharmaceutical compositions containing them, process producing them and their use
HUP9903836A2 (en) New process of preparing phenyl substituted 2(5h)-furanones having cox-2 inhibitor activity
TR199802160T2 (en) Azetidinone derivatives for the treatment of atherosclerosis.
YU15291A (en) HERBICIDAL EFFECTS OF CINNAMON ACID ESTERS
DE69719511D1 (en) ANTIVIRAL 2,4-PYRIMIDINDION DERIVATIVES AND METHOD FOR THE PRODUCTION THEREOF
MX9806251A (en) Dihydrobenzofuran and related compounds useful as anti-inflammatory agents.
ES2152563T3 (en) PROCEDURE TO PREPARE DERIVATIVES OF DIHYDROXIPIRIMIDINE.
TR200202129T2 (en) Processes for the preparation of new substituted propane derivatives.
ATE328055T1 (en) SUBSTITUTED LINEAR THIOUREA COMPOUNDS AS LUBRICANT ADDITIVES
ATE20234T1 (en) AROYLAMINO ACIDS.
DE60013188D1 (en) FUNGIIZIDE 6- (TRIFLUORMETHYL-PHENYL) -TRIAZOLPYRIMIDINE
TR200000117T2 (en) Process for the preparation of amine derivatives of alkyloxyfuranone.
DE69720718T2 (en) DIHYDROBENZOFURANES AND RELATED COMPOUNDS USEFUL AS AN ANTI-FLAMMING AGENT
ATE250594T1 (en) DIHYDROBENZOFURANES AND RELATED COMPOUNDS USEFUL AS ANTI-INFLAMMATORY AGENTS