CN107849040A - 三环衍生化合物、其制备方法、和含有其的药物组合物 - Google Patents
三环衍生化合物、其制备方法、和含有其的药物组合物 Download PDFInfo
- Publication number
- CN107849040A CN107849040A CN201680040992.8A CN201680040992A CN107849040A CN 107849040 A CN107849040 A CN 107849040A CN 201680040992 A CN201680040992 A CN 201680040992A CN 107849040 A CN107849040 A CN 107849040A
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- Prior art keywords
- bases
- methyl
- naphthyridines
- piperazine
- oxo
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Classifications
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- 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
- C07D401/06—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 carbon chain containing only aliphatic carbon atoms
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/4353—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems
- A61K31/4375—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a six-membered ring having nitrogen as a ring heteroatom, e.g. quinolizines, naphthyridines, berberine, vincamine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/4965—Non-condensed pyrazines
- A61K31/497—Non-condensed pyrazines containing further heterocyclic rings
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
Abstract
Description
Claims (19)
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KR10-2015-0081021 | 2015-06-09 | ||
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CN107849040A true CN107849040A (zh) | 2018-03-27 |
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EP (1) | EP3312177B1 (zh) |
JP (2) | JP2018521033A (zh) |
KR (1) | KR101837047B1 (zh) |
CN (1) | CN107849040B (zh) |
AU (1) | AU2016276806B9 (zh) |
BR (1) | BR112017026392B1 (zh) |
CA (1) | CA2990277C (zh) |
CL (1) | CL2017003138A1 (zh) |
DK (1) | DK3312177T3 (zh) |
ES (1) | ES2870203T3 (zh) |
MX (1) | MX2017016013A (zh) |
MY (1) | MY194590A (zh) |
NZ (1) | NZ738187A (zh) |
PH (1) | PH12017502228A1 (zh) |
PL (1) | PL3312177T3 (zh) |
PT (1) | PT3312177T (zh) |
RU (1) | RU2715413C2 (zh) |
SA (1) | SA517390509B1 (zh) |
WO (1) | WO2016200101A2 (zh) |
ZA (1) | ZA201708663B (zh) |
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CN114144413A (zh) * | 2019-07-19 | 2022-03-04 | 阿斯利康(瑞典)有限公司 | Parp1抑制剂 |
CN115232129A (zh) * | 2022-08-18 | 2022-10-25 | 上海闻耐医药科技有限公司 | 一种parp1选择性抑制剂及其制备方法和用途 |
WO2022222921A1 (zh) * | 2021-04-22 | 2022-10-27 | 微境生物医药科技(上海)有限公司 | 含哌嗪结构的parp抑制剂、其制备方法及医药用途 |
WO2022222966A1 (zh) * | 2021-04-23 | 2022-10-27 | 成都百裕制药股份有限公司 | 一种选择性parp1抑制剂及其应用 |
WO2022222995A1 (zh) * | 2021-04-23 | 2022-10-27 | 南京明德新药研发有限公司 | 吡啶酰胺类化合物 |
WO2023011608A1 (zh) * | 2021-08-05 | 2023-02-09 | 上海枢境生物科技有限公司 | 含三并环类衍生物调节剂、其制备方法和应用 |
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Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5391554A (en) * | 1992-09-09 | 1995-02-21 | Warner-Lambert Company | Dihydro- and tetrahydronaphthyridines |
WO2009061131A2 (en) * | 2007-11-06 | 2009-05-14 | Je Il Pharmaceutical Co., Ltd. | Novel tricyclic derivatives or pharmaceutically acceptable salts thereof, process for the preparation thereof and pharmaceutical composition comprising the same |
CN102245612A (zh) * | 2008-11-11 | 2011-11-16 | 第一药品株式会社 | 新型三环衍生物或其药物可接受的盐、其制备方法和含有它们的药物组合物 |
WO2013115535A1 (ko) * | 2012-02-01 | 2013-08-08 | 제일약품주식회사 | 트리사이클로 유도체 화합물의 신규한 결정형 산부가염 또는 이의 수화물 및 이의 제조방법 |
Family Cites Families (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
AUPS137402A0 (en) * | 2002-03-26 | 2002-05-09 | Fujisawa Pharmaceutical Co., Ltd. | Novel tricyclic compounds |
DE102004028973A1 (de) | 2004-06-16 | 2006-01-05 | Sanofi-Aventis Deutschland Gmbh | Substituierte Tetrahydro-2H-isochinolin-1-on-Derivate, Verfahren zu ihrer Herstellung und ihre Verwendung als Medikament |
DK2061765T3 (en) * | 2006-09-01 | 2015-01-26 | Senhwa Biosciences Inc | Serine-threonine protein kinase AND PARP-MODULATOR |
EP2215075B1 (en) | 2007-10-26 | 2013-12-11 | Janssen Pharmaceutica, N.V. | Quinolinone derivatives as parp inhibitors |
CA2990277C (en) * | 2015-06-09 | 2021-10-26 | Je Il Pharmaceutical Co., Ltd. | Tricyclic derivative compound, method for preparing same, and pharmaceutical composition comprising same |
KR101775356B1 (ko) * | 2015-07-06 | 2017-09-06 | 재단법인 아산사회복지재단 | Parp 및 탄키라제 동시 저해제에 대한 감수성 결정 방법 |
-
2016
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- 2016-06-03 AU AU2016276806A patent/AU2016276806B9/en active Active
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- 2016-06-03 PL PL16807741T patent/PL3312177T3/pl unknown
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- 2016-06-03 WO PCT/KR2016/005911 patent/WO2016200101A2/ko active Application Filing
-
2017
- 2017-12-07 CL CL2017003138A patent/CL2017003138A1/es unknown
- 2017-12-07 SA SA517390509A patent/SA517390509B1/ar unknown
- 2017-12-07 PH PH12017502228A patent/PH12017502228A1/en unknown
- 2017-12-19 ZA ZA2017/08663A patent/ZA201708663B/en unknown
-
2019
- 2019-05-09 JP JP2019088851A patent/JP6806969B2/ja active Active
Patent Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5391554A (en) * | 1992-09-09 | 1995-02-21 | Warner-Lambert Company | Dihydro- and tetrahydronaphthyridines |
WO2009061131A2 (en) * | 2007-11-06 | 2009-05-14 | Je Il Pharmaceutical Co., Ltd. | Novel tricyclic derivatives or pharmaceutically acceptable salts thereof, process for the preparation thereof and pharmaceutical composition comprising the same |
CN102245612A (zh) * | 2008-11-11 | 2011-11-16 | 第一药品株式会社 | 新型三环衍生物或其药物可接受的盐、其制备方法和含有它们的药物组合物 |
WO2013115535A1 (ko) * | 2012-02-01 | 2013-08-08 | 제일약품주식회사 | 트리사이클로 유도체 화합물의 신규한 결정형 산부가염 또는 이의 수화물 및 이의 제조방법 |
Cited By (18)
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WO2020155141A1 (zh) * | 2019-02-02 | 2020-08-06 | 中国科学院上海有机化学研究所 | 治疗神经退行性疾病或rna结合蛋白发生异常导致的疾病的药物组合物及其应用 |
CN114144413A (zh) * | 2019-07-19 | 2022-03-04 | 阿斯利康(瑞典)有限公司 | Parp1抑制剂 |
WO2022222921A1 (zh) * | 2021-04-22 | 2022-10-27 | 微境生物医药科技(上海)有限公司 | 含哌嗪结构的parp抑制剂、其制备方法及医药用途 |
CN115702156A (zh) * | 2021-04-23 | 2023-02-14 | 南京明德新药研发有限公司 | 吡啶酰胺类化合物 |
WO2022222966A1 (zh) * | 2021-04-23 | 2022-10-27 | 成都百裕制药股份有限公司 | 一种选择性parp1抑制剂及其应用 |
WO2022222995A1 (zh) * | 2021-04-23 | 2022-10-27 | 南京明德新药研发有限公司 | 吡啶酰胺类化合物 |
WO2023011608A1 (zh) * | 2021-08-05 | 2023-02-09 | 上海枢境生物科技有限公司 | 含三并环类衍生物调节剂、其制备方法和应用 |
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WO2023061406A1 (zh) * | 2021-10-12 | 2023-04-20 | 微境生物医药科技(上海)有限公司 | 含三并环结构的parp抑制剂、及其制备方法和医药用途 |
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WO2023169226A1 (en) * | 2022-03-11 | 2023-09-14 | Impact Therapeutics (Shanghai), Inc | Substituted tricyclic compounds as parp inhibitors and the use thereof |
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WO2024041605A1 (zh) * | 2022-08-24 | 2024-02-29 | 四川海思科制药有限公司 | 一种杂芳基衍生物parp抑制剂药学上可接受的盐及其用途 |
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