CA2843102A1 - Bicyclic pyrimidone compounds - Google Patents
Bicyclic pyrimidone compounds Download PDFInfo
- Publication number
- CA2843102A1 CA2843102A1 CA2843102A CA2843102A CA2843102A1 CA 2843102 A1 CA2843102 A1 CA 2843102A1 CA 2843102 A CA2843102 A CA 2843102A CA 2843102 A CA2843102 A CA 2843102A CA 2843102 A1 CA2843102 A1 CA 2843102A1
- Authority
- CA
- Canada
- Prior art keywords
- esi
- pyrimido
- chloro
- title compound
- ret time
- 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
Links
- -1 Bicyclic pyrimidone compounds Chemical class 0.000 title claims abstract description 34
- 238000000034 method Methods 0.000 claims abstract description 263
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 77
- 201000010099 disease Diseases 0.000 claims abstract description 65
- 208000024827 Alzheimer disease Diseases 0.000 claims abstract description 24
- 238000011282 treatment Methods 0.000 claims abstract description 22
- 201000001320 Atherosclerosis Diseases 0.000 claims abstract description 17
- 150000001875 compounds Chemical class 0.000 claims description 460
- 150000003839 salts Chemical class 0.000 claims description 210
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 42
- 229910052731 fluorine Inorganic materials 0.000 claims description 32
- 229910052739 hydrogen Inorganic materials 0.000 claims description 27
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 25
- 239000008194 pharmaceutical composition Substances 0.000 claims description 23
- 230000004770 neurodegeneration Effects 0.000 claims description 21
- 125000001072 heteroaryl group Chemical group 0.000 claims description 17
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 14
- 125000004076 pyridyl group Chemical group 0.000 claims description 13
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 11
- 239000003814 drug Substances 0.000 claims description 9
- 238000004519 manufacturing process Methods 0.000 claims description 7
- 229910052702 rhenium Inorganic materials 0.000 claims description 7
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 6
- 238000002560 therapeutic procedure Methods 0.000 claims description 6
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 5
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 5
- 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 claims description 4
- 125000001544 thienyl group Chemical group 0.000 claims description 4
- 239000001257 hydrogen Substances 0.000 claims description 3
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- QJIGPJZJKXZSNF-UHFFFAOYSA-N 8-[[3,5-difluoro-4-[6-(trifluoromethyl)pyridin-3-yl]oxyphenyl]methoxy]-1-methyl-3,4-dihydro-2h-pyrimido[1,2-c]pyrimidin-6-one Chemical compound CN1CCCN(C(N=2)=O)C1=CC=2OCC(C=C1F)=CC(F)=C1OC1=CC=C(C(F)(F)F)N=C1 QJIGPJZJKXZSNF-UHFFFAOYSA-N 0.000 claims 1
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- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 30
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- DPVIABCMTHHTGB-UHFFFAOYSA-N 2,4,6-trichloropyrimidine Chemical compound ClC1=CC(Cl)=NC(Cl)=N1 DPVIABCMTHHTGB-UHFFFAOYSA-N 0.000 description 16
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- 125000000217 alkyl group Chemical group 0.000 description 15
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Classifications
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
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- 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
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- 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
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- 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
- A61P3/06—Antihyperlipidemics
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- 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
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
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| CN2011077702 | 2011-07-27 | ||
| CNPCT/CN2011/077702 | 2011-07-27 | ||
| PCT/EP2012/064598 WO2013014185A1 (en) | 2011-07-27 | 2012-07-25 | Bicyclic pyrimidone compounds |
Publications (1)
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| CA2843102A1 true CA2843102A1 (en) | 2013-01-31 |
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| EP (1) | EP2736908A1 (enExample) |
| JP (1) | JP2014521625A (enExample) |
| KR (1) | KR20140059204A (enExample) |
| AR (1) | AR087309A1 (enExample) |
| AU (1) | AU2012288865B2 (enExample) |
| BR (1) | BR112014001634A2 (enExample) |
| CA (1) | CA2843102A1 (enExample) |
| RU (1) | RU2014107486A (enExample) |
| TW (1) | TW201321382A (enExample) |
| UY (1) | UY34216A (enExample) |
| WO (1) | WO2013014185A1 (enExample) |
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| EP2736908A1 (en) * | 2011-07-27 | 2014-06-04 | Glaxo Group Limited | Bicyclic pyrimidone compounds |
| EP2928873A1 (en) | 2012-11-27 | 2015-10-14 | Basf Se | Substituted 2-[phenoxy-phenyl]-1-[1,2,4]triazol-1-yl-ethanol compounds and their use as fungicides |
| EP2925730A1 (en) | 2012-11-27 | 2015-10-07 | Basf Se | Substituted 2-[phenoxy-phenyl]-1-[1,2,4]triazol-1-yl-ethanol compounds and their use as fungicides |
| US20150313229A1 (en) | 2012-11-27 | 2015-11-05 | Basf Se | Substituted [1,2,4] Triazole Compounds |
| CN104968665A (zh) * | 2013-01-25 | 2015-10-07 | 葛兰素史密斯克莱知识产权发展有限公司 | 作为lp-pla2抑制剂的双环嘧啶酮化合物 |
| RU2015135806A (ru) * | 2013-01-25 | 2017-03-03 | Глэксосмитклайн Интеллекчуал Проперти Дивелопмент Лимитед | Соединения |
| 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 |
| US9630896B2 (en) | 2013-11-22 | 2017-04-25 | Tansna Therapeutics, Inc. | 2,5-dialkyl-4-H/halo/ether-phenol compounds |
| 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 |
| CN106536521B (zh) | 2014-07-22 | 2018-08-03 | 葛兰素史密斯克莱知识产权发展有限公司 | 化合物 |
| 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 |
| CN105777653A (zh) | 2014-12-26 | 2016-07-20 | 中国科学院上海药物研究所 | 用作Lp-PLA2抑制剂的嘧啶酮类化合物及其药物组合物 |
| CN106188063A (zh) * | 2015-05-08 | 2016-12-07 | 中国科学院上海药物研究所 | 用作Lp-PLA2抑制剂的双环类化合物、其制备方法及医药用途 |
| WO2017040877A1 (en) * | 2015-09-04 | 2017-03-09 | Lysosomal Therapeutics Inc. | Heterobicyclic pyrimidinone compounds and their use in the treatment of medical disorders |
| GB201522179D0 (en) * | 2015-12-16 | 2016-01-27 | Autifony Therapeutics Ltd | Novel compounds |
| EP3752503A1 (en) | 2018-02-16 | 2020-12-23 | Boehringer Ingelheim International GmbH | Inhibitors of trpc6 |
| CN112574221B (zh) * | 2019-09-30 | 2022-03-04 | 上海纽思克生物科技有限公司 | 四环嘧啶酮类化合物、其制备方法、其组合物和用途 |
| MX2022005615A (es) | 2019-11-09 | 2022-07-27 | Shanghai Simr Biotechnology Co Ltd | Derivado triciclico de dihidroimidazopirimidona, metodo de preparacion del mismo, composicion farmaceutica y uso del mismo. |
| WO2021228159A1 (zh) * | 2020-05-13 | 2021-11-18 | 上海纽思克生物科技有限公司 | 桥环嘧啶酮类化合物、其制备方法、其组合物和用途 |
| CN113912622B (zh) * | 2020-07-10 | 2023-12-01 | 上海纽思克生物科技有限公司 | 三环嘧啶酮类化合物、其制备方法、其组合物和用途 |
| 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 |
Family Cites Families (42)
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| CN1175246A (zh) | 1994-12-22 | 1998-03-04 | 史密丝克莱恩比彻姆有限公司 | 用于治疗动脉粥样硬化的取代的氮杂环丁－2－酮 |
| CH690264A5 (fr) | 1995-06-30 | 2000-06-30 | Symphar Sa | Dérivés aminophosphonates substitués, leur procédé de préparation et leur utilisation pour la préparation de compositions pharmaceutiques. |
| HUP9901153A3 (en) | 1995-07-01 | 1999-11-29 | Smithkline Beecham Plc | Azetidinone derivatives for the treatment of atherosclerosis, their production and pharmaceutical compositions containing them |
| EP0859834A2 (en) | 1995-09-29 | 1998-08-26 | Smithkline Beecham Plc | A paf-acetylhydrolase and use in therapy |
| JP2000505063A (ja) | 1995-12-08 | 2000-04-25 | 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 | アテローム性動脈硬化症の治療のためのアゼチジノン化合物 |
| EP0869943A1 (en) | 1995-12-08 | 1998-10-14 | Smithkline Beecham Plc | Monocyclic beta-lactame derivatives for treatment of atherosclerosis |
| GB9608649D0 (en) | 1996-04-26 | 1996-07-03 | Smithkline Beecham Plc | Novel compounds |
| CZ341098A3 (cs) | 1996-04-26 | 1999-03-17 | Smithkline Beecham Plc | Azetidinonové deriváty pro ošetřování aterosklerózy |
| GB9626615D0 (en) | 1996-12-20 | 1997-02-05 | Symphar Sa | Novel compounds |
| GB9626536D0 (en) | 1996-12-20 | 1997-02-05 | Symphar Sa | Novel compounds |
| GB9626616D0 (en) | 1996-12-20 | 1997-02-05 | Symphar Sa | Novel compounds |
| 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 |
| EP1105377B1 (en) | 1998-08-21 | 2003-10-08 | SmithKline Beecham plc | Pyrimidinone derivatives for the treatment of atherosclerosis |
| GB9910079D0 (en) | 1999-05-01 | 1999-06-30 | Smithkline Beecham Plc | Novel compounds |
| DE60016397T2 (de) | 1999-05-01 | 2005-12-01 | Smithkline Beecham P.L.C., Brentford | Pyrimidinonverbindung(en) |
| GB9910378D0 (en) | 1999-05-05 | 1999-06-30 | Smithkline Beecham Plc | Novel compounds |
| JP3757703B2 (ja) | 1999-09-22 | 2006-03-22 | 凸版印刷株式会社 | 再封可能な開口維持部材付パウチ |
| CZ304450B6 (cs) | 2000-02-16 | 2014-05-14 | Smithkline Beecham P. L. C. | Pyrimidinový derivát |
| GB0024808D0 (en) | 2000-10-10 | 2000-11-22 | Smithkline Beecham Plc | Novel compounds |
| GB0024807D0 (en) | 2000-10-10 | 2000-11-22 | Smithkline Beecham Plc | Novel compounds |
| GB0119795D0 (en) | 2001-08-14 | 2001-10-03 | Smithkline Beecham Plc | Novel process |
| GB0119793D0 (en) | 2001-08-14 | 2001-10-03 | Smithkline Beecham Plc | Novel compounds |
| GB0127140D0 (en) | 2001-11-10 | 2002-01-02 | Smithkline Beecham | Novel compounds |
| GB0127143D0 (en) | 2001-11-10 | 2002-01-02 | Smithkline Beecham | Novel compounds |
| GB0127139D0 (en) | 2001-11-10 | 2002-01-02 | Smithkline Beecham | Novel compounds |
| GB0127141D0 (en) | 2001-11-10 | 2002-01-02 | Smithkline Beecham Plc | Novel compounds |
| GB0208280D0 (en) * | 2002-04-10 | 2002-05-22 | Glaxo Group Ltd | Novel compounds |
| GB0208279D0 (en) | 2002-04-10 | 2002-05-22 | Glaxo Group Ltd | Novel compounds |
| CA2530816A1 (en) | 2003-07-02 | 2005-01-13 | Bayer Healthcare Ag | Amide-substituted 1,2,4-triazin-5(2h)-ones for the treatment of chronic inflammatory diseases |
| DE102004061008A1 (de) | 2004-12-18 | 2006-06-22 | Bayer Healthcare Ag | 3-Arylalkyl- und 3-Heteroarylalkyl-substituierte 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 |
| US7705005B2 (en) | 2006-10-13 | 2010-04-27 | Glaxo Group Limited | Bicyclic heteroaromatic compounds |
| WO2008048867A2 (en) | 2006-10-13 | 2008-04-24 | Glaxo Group Limited | Bicyclic heteroaromatic compounds |
| US20080090852A1 (en) | 2006-10-13 | 2008-04-17 | Colin Andrew Leach | Bicyclic Heteroaromatic Compounds |
| US20080090851A1 (en) | 2006-10-13 | 2008-04-17 | Colin Andrew Leach | Bicyclic Heteroaromatic Compounds |
| US20080279846A1 (en) | 2007-05-11 | 2008-11-13 | Thomas Jefferson University | 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 |
| CN101687009A (zh) | 2007-05-11 | 2010-03-31 | 宾夕法尼亚大学理事会 | 治疗皮肤溃疡的方法 |
| ES2456966T3 (es) * | 2007-11-12 | 2014-04-24 | Takeda Pharmaceutical Company Limited | Inhibidores de MAPK/ERK cinasa |
| JP2011088847A (ja) * | 2009-10-21 | 2011-05-06 | Takeda Chem Ind Ltd | 三環性化合物およびその用途 |
| EP2736908A1 (en) * | 2011-07-27 | 2014-06-04 | Glaxo Group Limited | Bicyclic pyrimidone compounds |
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2012
- 2012-07-25 EP EP12738465.9A patent/EP2736908A1/en not_active Withdrawn
- 2012-07-25 RU RU2014107486/04A patent/RU2014107486A/ru not_active Application Discontinuation
- 2012-07-25 TW TW101126715A patent/TW201321382A/zh unknown
- 2012-07-25 AR ARP120102692A patent/AR087309A1/es not_active Application Discontinuation
- 2012-07-25 US US14/234,687 patent/US9273054B2/en not_active Expired - Fee Related
- 2012-07-25 JP JP2014522075A patent/JP2014521625A/ja not_active Ceased
- 2012-07-25 US US13/557,498 patent/US20130030012A1/en not_active Abandoned
- 2012-07-25 KR KR1020147004716A patent/KR20140059204A/ko not_active Withdrawn
- 2012-07-25 CA CA2843102A patent/CA2843102A1/en not_active Abandoned
- 2012-07-25 UY UY0001034216A patent/UY34216A/es unknown
- 2012-07-25 AU AU2012288865A patent/AU2012288865B2/en not_active Ceased
- 2012-07-25 WO PCT/EP2012/064598 patent/WO2013014185A1/en not_active Ceased
- 2012-07-25 BR BR112014001634A patent/BR112014001634A2/pt not_active IP Right Cessation
Also Published As
| Publication number | Publication date |
|---|---|
| US20140179716A1 (en) | 2014-06-26 |
| UY34216A (es) | 2013-02-28 |
| AU2012288865B2 (en) | 2015-10-01 |
| AR087309A1 (es) | 2014-03-12 |
| TW201321382A (zh) | 2013-06-01 |
| KR20140059204A (ko) | 2014-05-15 |
| US9273054B2 (en) | 2016-03-01 |
| RU2014107486A (ru) | 2015-09-10 |
| JP2014521625A (ja) | 2014-08-28 |
| WO2013014185A1 (en) | 2013-01-31 |
| BR112014001634A2 (pt) | 2017-02-14 |
| AU2012288865A1 (en) | 2014-02-13 |
| EP2736908A1 (en) | 2014-06-04 |
| US20130030012A1 (en) | 2013-01-31 |
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