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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| CNPCT/CN2011/077702 | 2011-07-27 | ||
| CN2011077702 | 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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| AU2012288865B2 (en) * | 2011-07-27 | 2015-10-01 | Glaxo Group Limited | Bicyclic pyrimidone compounds |
| EP2925732A1 (en) | 2012-11-27 | 2015-10-07 | Basf Se | Substituted [1,2,4]triazole compounds |
| CN105008336A (zh) | 2012-11-27 | 2015-10-28 | 巴斯夫欧洲公司 | 取代2-[苯氧基苯基]-1-[1,2,4]三唑-1-基乙醇化合物及其作为杀真菌剂的用途 |
| US20160029630A1 (en) | 2012-11-27 | 2016-02-04 | Basf Se | Substituted 2-[phenoxy-phenyl]-1-[1,2,4]triazol-1-yl-ethanol compounds and their use as fungicides |
| 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 |
| 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 |
| EP2948457A4 (en) * | 2013-01-25 | 2016-09-07 | Glaxosmithkline Ip Dev Ltd | COMPOUNDS |
| 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 |
| 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 |
| ES2744339T3 (es) * | 2014-07-22 | 2020-02-24 | Glaxosmithkline Ip Dev Ltd | Compuestos |
| 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 |
| US20190092789A1 (en) * | 2015-09-04 | 2019-03-28 | 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 |
| CN111868055B (zh) | 2018-02-16 | 2024-03-08 | 勃林格殷格翰国际有限公司 | Trpc6的抑制剂 |
| 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 |
| BR112022008786A2 (pt) | 2019-11-09 | 2022-07-26 | Shanghai Simr Biotechnology Co Ltd | Composto, composição, uso do composto ou da composição, e, método para tratar ou prevenir uma complicação diabética, doença relacionada à neuroinflamação ou aterosclerose |
| EP4151638A4 (en) * | 2020-05-13 | 2024-06-12 | Neusco Biotech Limited | BRIDGED CYCLIC PYRIMIDINONE COMPOUND, METHOD FOR PREPARING IT, COMPOSITION CONTAINING IT AND ITS USE |
| 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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| FI972584L (fi) | 1994-12-22 | 1997-08-19 | Smithkline Beecham Plc | Substituoituja atsetidin-2-oneja ateroskleroosin hoitamiseksi |
| 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. |
| WO1997002242A1 (en) | 1995-07-01 | 1997-01-23 | Smithkline Beecham Plc | Azetidinone derivatives for the treatment of atherosclerosis |
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| 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 |
| CA2252696A1 (en) | 1996-04-26 | 1997-11-06 | Deirdre Mary Bernadette Hickey | Azetidinone derivatives for the treatment of atherosclerosis |
| GB9608649D0 (en) | 1996-04-26 | 1996-07-03 | Smithkline Beecham Plc | Novel compounds |
| GB9626536D0 (en) | 1996-12-20 | 1997-02-05 | Symphar Sa | Novel compounds |
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| WO1999024420A1 (en) | 1997-11-06 | 1999-05-20 | Smithkline Beecham Plc | Pyrimidinone compounds and pharmaceutical compositions containing them |
| DE69911980T2 (de) | 1998-08-21 | 2004-09-09 | Smithkline Beecham P.L.C., Brentford | Pyrimidinonderivate zur behandlung von atheroscleros |
| GB9910079D0 (en) | 1999-05-01 | 1999-06-30 | Smithkline Beecham Plc | Novel compounds |
| ATE283845T1 (de) | 1999-05-01 | 2004-12-15 | Smithkline Beecham Plc | Pyrimidinon verbindungen |
| 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 |
| NZ520752A (en) | 2000-02-16 | 2004-03-26 | Smithkline Beecham P | Pyrimidine-4-one derivatives as LDL-PLA2 inhibitors |
| GB0024808D0 (en) | 2000-10-10 | 2000-11-22 | Smithkline Beecham Plc | Novel compounds |
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| GB0127139D0 (en) | 2001-11-10 | 2002-01-02 | Smithkline Beecham | Novel compounds |
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| GB0127141D0 (en) | 2001-11-10 | 2002-01-02 | Smithkline Beecham Plc | Novel compounds |
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| 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 |
| EP1644353A1 (de) | 2003-07-02 | 2006-04-12 | Bayer HealthCare AG | Amid-substituierte 1, 2, 4-triazin-5 (2h) - one zur behandlung von chronisch inflammatorischen krankheiten |
| 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 |
| US20080090851A1 (en) | 2006-10-13 | 2008-04-17 | Colin Andrew Leach | Bicyclic Heteroaromatic Compounds |
| US7705005B2 (en) | 2006-10-13 | 2010-04-27 | Glaxo Group Limited | Bicyclic heteroaromatic compounds |
| EP2083625A4 (en) | 2006-10-13 | 2011-10-19 | Glaxo Group Ltd | BICYCLIC HETOROAROMATIC COMPOUNDS |
| US20080090852A1 (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 |
| ES2548878T3 (es) | 2007-05-11 | 2015-10-21 | The Trustees Of The University Of Pennsylvania | Métodos de tratamiento de úlceras de la piel |
| US8962633B2 (en) | 2007-05-11 | 2015-02-24 | Thomas Jefferson University | Methods of treatment and prevention of metabolic bone diseases and disorders |
| US8022057B2 (en) * | 2007-11-12 | 2011-09-20 | Takeda Pharmaceutical Company Limited | MAPK/ERK kinase inhibitors |
| 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 |
| AU2012288865B2 (en) * | 2011-07-27 | 2015-10-01 | Glaxo Group Limited | Bicyclic pyrimidone compounds |
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- 2012-07-25 AU AU2012288865A patent/AU2012288865B2/en not_active Ceased
- 2012-07-25 EP EP12738465.9A patent/EP2736908A1/en not_active Withdrawn
- 2012-07-25 BR BR112014001634A patent/BR112014001634A2/pt not_active IP Right Cessation
- 2012-07-25 CA CA2843102A patent/CA2843102A1/en not_active Abandoned
- 2012-07-25 WO PCT/EP2012/064598 patent/WO2013014185A1/en not_active Ceased
- 2012-07-25 US US14/234,687 patent/US9273054B2/en not_active Expired - Fee Related
- 2012-07-25 AR ARP120102692A patent/AR087309A1/es not_active Application Discontinuation
- 2012-07-25 UY UY0001034216A patent/UY34216A/es unknown
- 2012-07-25 US US13/557,498 patent/US20130030012A1/en not_active Abandoned
- 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 KR KR1020147004716A patent/KR20140059204A/ko not_active Withdrawn
- 2012-07-25 JP JP2014522075A patent/JP2014521625A/ja not_active Ceased
Also Published As
| Publication number | Publication date |
|---|---|
| JP2014521625A (ja) | 2014-08-28 |
| AR087309A1 (es) | 2014-03-12 |
| EP2736908A1 (en) | 2014-06-04 |
| US9273054B2 (en) | 2016-03-01 |
| US20140179716A1 (en) | 2014-06-26 |
| TW201321382A (zh) | 2013-06-01 |
| BR112014001634A2 (pt) | 2017-02-14 |
| AU2012288865B2 (en) | 2015-10-01 |
| WO2013014185A1 (en) | 2013-01-31 |
| UY34216A (es) | 2013-02-28 |
| AU2012288865A1 (en) | 2014-02-13 |
| KR20140059204A (ko) | 2014-05-15 |
| RU2014107486A (ru) | 2015-09-10 |
| US20130030012A1 (en) | 2013-01-31 |
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