PE20010070A1 - COMPUESTOS DE PIRIMIDINONA COMO INHIBIDORES DE LA ENZIMA Lp-PLA2 - Google Patents

COMPUESTOS DE PIRIMIDINONA COMO INHIBIDORES DE LA ENZIMA Lp-PLA2

Info

Publication number
PE20010070A1
PE20010070A1 PE2000000399A PE0003992000A PE20010070A1 PE 20010070 A1 PE20010070 A1 PE 20010070A1 PE 2000000399 A PE2000000399 A PE 2000000399A PE 0003992000 A PE0003992000 A PE 0003992000A PE 20010070 A1 PE20010070 A1 PE 20010070A1
Authority
PE
Peru
Prior art keywords
alkyl
optionally substituted
compounds
methyl
pyrimidinone compounds
Prior art date
Application number
PE2000000399A
Other languages
English (en)
Inventor
Ashley Edward Fenwick
Deirdre Mary Bernadette Hickey
Robert John Ife
Colin Andrew Leach
Ivan Leo Pinto
Stephen Allan Smith
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 GB9910048A external-priority patent/GB9910048D0/en
Priority claimed from GB0002096A external-priority patent/GB0002096D0/en
Application filed by Smithkline Beecham Plc filed Critical Smithkline Beecham Plc
Publication of PE20010070A1 publication Critical patent/PE20010070A1/es

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
    • C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
    • C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
    • C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
    • C07D239/46—Two or more oxygen, sulphur or nitrogen atoms
    • C07D239/56—One oxygen atom and one sulfur atom
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
    • A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • 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
    • A61P9/08—Vasodilators for multiple indications
    • 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
    • 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
    • A61P9/12—Antihypertensives
    • 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
    • C07D401/14—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 three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
    • C07D403/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms

Abstract

SE REFIERE A COMPUESTOS DE PIRIMIDINONA DE FORMULA I, DONDE: R1 ES ARILO, HETEROARILO OPCIONALMENTE CON ALQUILO C1-C18, OH, HALOGENO, CN, NR6COR7, ENTRE OTROS; R2 ES ARILO, HETEROARILO, OPCIONALMENTE SUSTITUIDO CON ALQUILO C1-C18, ENTRE OTROS; R3 ES H, ALQUILO C1-C4 OPCIONALMENTE SUSTITUIDO CON OH, OR6, COR6, CARBOXI, COOR6, CONR9R10, NR9R10, ENTRE OTROS; R4 ES ARIL, HETEROARIL OPCIONALMENTE SUSTITUIDO CON ALQUILO C1-C18, ALCOXI C1-C18, ENTRE OTROS; R5 ES ARIL, HETEROARIL OPCIONALMENTE SUSTITUIDO CON ALQUILO C1-C18, ALCOXI C1-C18, NR6COR7, ENTRE OTROS; R6 Y R7 SON H, ALQUILO C1-C20; R8 ES ALQUILO C1-C4, R9 Y R10 SON H, ALQUILO C1-C12, ENTRE OTROS; n ES 1-4; X ES O, S; Z ES CR13R14; R13 Y R14 SON H, ALQUILO C1-C4 O JUNTO A C FORMAN UN CICLOALQUILO C3-C6. SON COMPUESTOS PREFERIDOS 1-(N-METIL-N-(4-(4-CLOROFENIL)BENCIL)AMINOCARBONILMETIL)-2-(4-FLUOROBENCIL)TIO-5-(1-METIL-PIRAZOL-4-ILMETIL)PIRIMIDIN-4-ONA; 1-(N-METIL-N-(4-(4-TRIFLUOROMETILFENIL)BENCIL)AMINOCARBONILMETIL-2-(4-FLUOROBENCIL)TIO-5-(1-METILPIRAZOL-4-ILMETIL)PIRIMIDIN-4-ONA, ENTRE OTROS. SE REFIERE TAMBIEN A UN PROCEDIMIENTO PARA LA PREPARACION Y A COMPUESTOS INTERMEDIOS. LOS COMPUESTOS DE PIRIMIDINONA SON INHIBIDORES DE LA ENZIMA FOSFOLIPASA A2 ASOCIADA A LAS LIPOPROTEINAS (Lp-LPA2) Y PUEDEN SER UTILES EN EL TRATAMIENTO DE ATEROSCLEROSIS
PE2000000399A 1999-05-01 2000-04-28 COMPUESTOS DE PIRIMIDINONA COMO INHIBIDORES DE LA ENZIMA Lp-PLA2 PE20010070A1 (es)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
GB9910048A GB9910048D0 (en) 1999-05-01 1999-05-01 Novel compounds
GB0002096A GB0002096D0 (en) 2000-01-28 2000-01-28 Novel compounds

Publications (1)

Publication Number Publication Date
PE20010070A1 true PE20010070A1 (es) 2001-03-10

Family

ID=26243514

Family Applications (1)

Application Number Title Priority Date Filing Date
PE2000000399A PE20010070A1 (es) 1999-05-01 2000-04-28 COMPUESTOS DE PIRIMIDINONA COMO INHIBIDORES DE LA ENZIMA Lp-PLA2

Country Status (29)

Country Link
US (2) US6953803B1 (es)
EP (2) EP1175408B1 (es)
JP (1) JP2002543190A (es)
KR (1) KR20020012200A (es)
CN (1) CN1286822C (es)
AR (1) AR023777A1 (es)
AT (2) ATE432265T1 (es)
AU (1) AU766003B2 (es)
BR (1) BR0010220A (es)
CA (1) CA2371671A1 (es)
CO (1) CO5170521A1 (es)
CZ (1) CZ20013904A3 (es)
DE (2) DE60016397T2 (es)
DK (1) DK1175408T3 (es)
ES (1) ES2233361T3 (es)
HK (1) HK1044757B (es)
HU (1) HUP0201122A3 (es)
IL (1) IL146210A0 (es)
MX (1) MXPA01011186A (es)
MY (1) MY136037A (es)
NO (1) NO20015329D0 (es)
NZ (1) NZ515137A (es)
PE (1) PE20010070A1 (es)
PL (1) PL351690A1 (es)
PT (1) PT1175408E (es)
SI (1) SI1175408T1 (es)
TR (1) TR200103216T2 (es)
UY (1) UY26132A1 (es)
WO (1) WO2000066567A1 (es)

Families Citing this family (35)

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BR0010220A (pt) * 1999-05-01 2002-05-14 Smithkline Beecham Plc Compostos de pirimidinona
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
GB0119793D0 (en) * 2001-08-14 2001-10-03 Smithkline Beecham Plc Novel compounds
GB0127139D0 (en) * 2001-11-10 2002-01-02 Smithkline Beecham Novel compounds
GB0127143D0 (en) * 2001-11-10 2002-01-02 Smithkline Beecham Novel compounds
GB0208280D0 (en) * 2002-04-10 2002-05-22 Glaxo Group Ltd Novel compounds
WO2005003118A1 (de) * 2003-07-02 2005-01-13 Bayer Healthcare Ag Amid-substituierte 1,2,4-triazin-5 (2h)-one zur behandlung von chronisch inflammatorischen krankheiten
US20150017671A1 (en) 2004-04-16 2015-01-15 Yaping Shou Methods for detecting lp-pla2 activity and inhibition of lp-pla2 activity
EP1735457A4 (en) 2004-04-16 2007-08-29 Glaxo Group Ltd METHODS FOR DETECTING Lp-PLA2 ACTIVITY AND INHIBITION OF Lp-PLA2 ACTIVITY
DE102004061006A1 (de) * 2004-12-18 2006-06-22 Bayer Healthcare Ag 3-Benzylthio-1,2,4-triazin-5(2H)-one
DE102004061009A1 (de) * 2004-12-18 2006-06-22 Bayer Healthcare Ag Substituierte 1,2,4-Triazin-5(2H)-one
CN1954826A (zh) * 2005-10-26 2007-05-02 上海生物芯片有限公司 银杏叶提取物在降低胆固醇方面的用途
KR101461659B1 (ko) 2007-05-11 2014-11-17 토마스 제퍼슨 유니버시티 신경변성 질환 및 장애의 치료 및 예방 방법
WO2008141176A1 (en) 2007-05-11 2008-11-20 The Trustees Of The University Of Pennsylvania Methods of treatment of skin ulcers
TW201209043A (en) * 2010-05-17 2012-03-01 Glaxo Group Ltd Novel processes
CN104478812A (zh) * 2010-12-06 2015-04-01 葛兰素集团有限公司 用于治疗由Lp-PLA2介导的疾病或病症的嘧啶酮化合物
JP5886310B2 (ja) 2010-12-06 2016-03-16 グラクソ グループ リミテッドＧｌａｘｏ Ｇｒｏｕｐ Ｌｉｍｉｔｅｄ Ｌｐ−ＰＬＡ２により媒介される疾患または状態の処置における使用のためのピリミジノン化合物
EP2651403B1 (en) 2010-12-17 2020-12-02 Glaxo Group Limited Use of lp-pla2 inhibitors in the treatment and prevention of eye diseases
WO2013000108A1 (zh) * 2011-06-27 2013-01-03 中国科学院上海药物研究所 唑类杂环化合物、其制备方法、药物组合物和用途
BR112014001665A2 (pt) 2011-07-27 2017-02-14 Glaxo Group Ltd compostos de 2,3-di-hidroimidazo[1,2-c]pirimidin-5(1h)-ona utilizados como inibidores de lp-plaz
RU2014107486A (ru) 2011-07-27 2015-09-10 Глэксо Груп Лимитед Бициклические пиримидоновые соединения
CA2853024C (en) * 2011-11-11 2017-08-22 Pfizer Inc. 2-thiopyrimidinones
JP2016505053A (ja) 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 Ｌｐ‐ＰＬＡ２の阻害剤としての二環式ピリミドン化合物
UY35276A (es) 2013-01-25 2014-08-29 Glaxosmithkline Ip Dev Ltd Nuevos compuestos que inhiben la actividad de Lp-PLA2
WO2014114248A1 (en) 2013-01-25 2014-07-31 Glaxosmithkline Intellectual Property Development Limited Compounds
US20140283157A1 (en) 2013-03-15 2014-09-18 Diadexus, Inc. Lipoprotein-associated phospholipase a2 antibody compositions and methods of use
US9552473B2 (en) 2014-05-14 2017-01-24 Microsoft Technology Licensing, Llc Claiming data from a virtual whiteboard
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
CN104840963B (zh) * 2015-05-26 2018-02-16 河北东康生物科技有限公司 含脂蛋白相关性磷脂酶a2抑制剂的药物组合物及应用
CN106008362B (zh) * 2016-05-24 2018-08-10 杰达维（上海）医药科技发展有限公司 一种嘧啶衍生物的制备方法
JP6545747B2 (ja) * 2017-05-09 2019-07-17 山田化学工業株式会社 色素化合物
CN112778331B (zh) 2019-11-09 2022-07-05 上海赛默罗生物科技有限公司 三环二氢咪唑并嘧啶酮衍生物、其制备方法、药物组合物和用途
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

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GB1582527A (en) * 1975-12-29 1981-01-07 Smith Kline French Lab Pyrimidone and thiopyrimidone derivatives
JP2001522844A (ja) * 1997-11-06 2001-11-20 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 ピリミジノン化合物およびそれを含有する医薬組成物
ATE251613T1 (de) 1998-08-21 2003-10-15 Smithkline Beecham Plc Pyrimidinonderivate zur behandlung von atheroscleros
BR0010220A (pt) * 1999-05-01 2002-05-14 Smithkline Beecham Plc Compostos de pirimidinona

Also Published As

Publication number Publication date
CA2371671A1 (en) 2000-11-09
CN1358175A (zh) 2002-07-10
CO5170521A1 (es) 2002-06-27
DE60016397T2 (de) 2005-12-01
AU766003B2 (en) 2003-10-09
IL146210A0 (en) 2002-07-25
KR20020012200A (ko) 2002-02-15
EP1175408A1 (en) 2002-01-30
PL351690A1 (en) 2003-06-02
EP1175408B1 (en) 2004-12-01
US7115616B2 (en) 2006-10-03
ATE432265T1 (de) 2009-06-15
ES2233361T3 (es) 2005-06-16
PT1175408E (pt) 2005-04-29
HUP0201122A3 (en) 2003-11-28
US6953803B1 (en) 2005-10-11
AR023777A1 (es) 2002-09-04
EP1479671B1 (en) 2009-05-27
UY26132A1 (es) 2000-12-29
MY136037A (en) 2008-08-29
CZ20013904A3 (cs) 2002-04-17
BR0010220A (pt) 2002-05-14
NZ515137A (en) 2003-10-31
US20040167142A1 (en) 2004-08-26
AU4120300A (en) 2000-11-17
DE60016397D1 (de) 2005-01-05
HK1044757B (zh) 2005-07-08
HUP0201122A2 (en) 2002-08-28
CN1286822C (zh) 2006-11-29
WO2000066567A1 (en) 2000-11-09
ATE283845T1 (de) 2004-12-15
DK1175408T3 (da) 2005-04-11
NO20015329L (no) 2001-10-31
EP1479671A1 (en) 2004-11-24
SI1175408T1 (en) 2005-04-30
TR200103216T2 (tr) 2002-04-22
DE60042286D1 (de) 2009-07-09
JP2002543190A (ja) 2002-12-17
MXPA01011186A (es) 2002-08-12
HK1044757A1 (en) 2002-11-01
NO20015329D0 (no) 2001-10-31

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