RU2017133419A - Производные пиримидина в качестве ингибиторов киназы и их терапевтические применения - Google Patents
Производные пиримидина в качестве ингибиторов киназы и их терапевтические применения Download PDFInfo
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- 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
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- A61K31/403—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
- A61K31/404—Indoles, e.g. pindolol
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- 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
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
-
- 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
- A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
- A61K31/5375—1,4-Oxazines, e.g. morpholine
- A61K31/5377—1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
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- 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]
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
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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
- C07D401/14—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
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- 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
- C07D403/12—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 chain containing hetero atoms as chain links
-
- 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
- C07D403/14—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 three or more hetero rings
-
- 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
- C07D405/14—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 three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
-
- 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
- C07D417/14—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 three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- 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
Claims (22)
1. Соединение формулы
или его фармацевтически приемлемая соль, в которой:
W выбирают из группы, состоящей из
: F, Cl, Br, I, CN, C1-C4алкила, C1-C6алкокси, C2-C6алкенила, CF3, CF2H, CFH2, C2-C6алкинила, CON(R1)R2;
R1 и R2 представляют собой водород, алкил, циклоалкил, алкенил, алкинил, алкилтио, арил, арилалкил;
Ar представляет собой гетероарил или арил, каждый из которых замещен от 0 до 4 заместителями, независимо выбранными из группы, состоящей из:
(1) галогена, гидрокси, амино, амида, циано, -COOH, -SO2NH2, оксо, нитро и алкоксикарбонила;
(2) NR1; и
(3) групп формулы (Ia):
(Ia)
в которой:
R4 представляет собой водород, C1-C4алкил или оксо;
X-R3 представляет собой СН; или X-R3 представляет собой O; или Х представляет собой N, и R3 представляет собой водород, С1-С6алкил, С2-С6алкенил, С2-С6алкинил, С3-С10арил или гетероарил, (С3-С7циклоалкил)C1-C4алкил, C1-C6галогеналкил, C1-C6алкокси, C1-C6алкилтио, C2-C6алканоил, C1-C6алкоксикарбонил, C2-C6алканоилокси, моно- и ди-(С3-С8циклоалкил)аминоC0-C4алкил, (4-7-членный гетероцикл)C0-C4алкил, C1-C6алкилсульфонил, моно- и ди-(C1-C6алкил)сульфонамидо и моно- и ди-(C1-C6алкил)аминокарбонил, каждый из которых замещен от 0 до 4 заместителями, независимо выбранными из галогена, гидрокси, циано, амино, -СООН или оксо;
R5 и R6 независимо выбраны из группы, состоящей из: водорода, F, Cl, Br, CN, С1-С4алкила и C1-C6алкокси; и
R7, R8 и R9 независимо выбраны из группы, состоящей из: водорода, С1-С4алкила, С2-С6алкенила, С2-С6алкинила, С3-С10арила или гетероарила, C1-C6алкокси, C1-C6алкилтио, С2-С6алканоила, C1-C6алкоксикарбонила и С2-С6алканоилокси.
2. Фармацевтическая композиция, содержащая, по меньшей мере, одно соединение по п.1 или его фармацевтически приемлемые соли, гидраты, сольваты, кристаллические формы соли, и их отдельные диастереомеры, и фармацевтически приемлемый носитель.
3. Способ лечения заболевания или состояния у млекопитающего, характеризующегося нежелательной клеточной пролиферацией или гиперпролиферацией, включающий идентификацию млекопитающего, страдающего указанным заболеванием или состоянием, и введение указанному страдающему млекопитающему композиции, содержащей соединение по п.1.
4. Способ лечения и/или профилактики пролиферативного нарушения, рака, опухоли, воспалительного заболевания, аутоиммунного заболевания или иммунологически родственного заболевания, который включает введение объекту, нуждающемуся в таком лечении, эффективного количества соединения по любому из пп.1 или фармацевтической композиции по п.2.
5. Применение соединения по п.1 для получения лекарственного средства.
6. Комбинация для лечения и/или профилактики пролиферативного нарушения, рака, опухоли, воспалительного заболевания, аутоиммунного заболевания или иммунологически родственного заболевания у объекта, которая содержит эффективное количество соединения по п.1 или его фармацевтически приемлемой соли и эффективное количество второго профилактического или терапевтического средства для лечения и/или профилактики пролиферативного нарушения, рака, опухоли, воспалительного заболевания, аутоиммунного заболевания или иммунологически родственного заболевания у объекта.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| PCT/US2015/018085 WO2016137506A1 (en) | 2015-02-27 | 2015-02-27 | Pyrimidine derivatives as kinase inhibitors and their therapeutical applications |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| RU2017133419A true RU2017133419A (ru) | 2019-03-27 |
| RU2017133419A3 RU2017133419A3 (ru) | 2019-03-27 |
| RU2701188C2 RU2701188C2 (ru) | 2019-09-25 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| RU2017133419A RU2701188C2 (ru) | 2015-02-27 | 2015-02-27 | Производные пиримидина в качестве ингибиторов киназы и их терапевтические применения |
| RU2017133448A RU2718915C2 (ru) | 2015-02-27 | 2016-02-29 | Производные пиримидина в качестве ингибиторов киназ и их терапевтические применения |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| RU2017133448A RU2718915C2 (ru) | 2015-02-27 | 2016-02-29 | Производные пиримидина в качестве ингибиторов киназ и их терапевтические применения |
Country Status (13)
| Country | Link |
|---|---|
| US (2) | US10766879B2 (ru) |
| EP (2) | EP3261637B1 (ru) |
| JP (2) | JP6444525B2 (ru) |
| KR (2) | KR20170122782A (ru) |
| CN (2) | CN107708690B (ru) |
| AU (2) | AU2015383881B2 (ru) |
| BR (2) | BR112017018183A2 (ru) |
| CA (2) | CA2977764C (ru) |
| ES (1) | ES2746007T3 (ru) |
| HK (2) | HK1248600B (ru) |
| IL (2) | IL254152B (ru) |
| RU (2) | RU2701188C2 (ru) |
| WO (2) | WO2016137506A1 (ru) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2016137506A1 (en) * | 2015-02-27 | 2016-09-01 | Nantbioscience, Inc. | Pyrimidine derivatives as kinase inhibitors and their therapeutical applications |
| CN108530361A (zh) * | 2018-05-17 | 2018-09-14 | 重庆医药高等专科学校 | 一种5-[2-(3,5-二甲氧基苯基)乙基]-1h-吡唑-3-胺的合成工艺 |
| CN113354599B (zh) * | 2021-08-09 | 2021-10-26 | 长沙康鹏医药有限公司 | 尼达尼布关键中间体的制备方法 |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5916596A (en) | 1993-02-22 | 1999-06-29 | Vivorx Pharmaceuticals, Inc. | Protein stabilized pharmacologically active agents, methods for the preparation thereof and methods for the use thereof |
| US6096331A (en) | 1993-02-22 | 2000-08-01 | Vivorx Pharmaceuticals, Inc. | Methods and compositions useful for administration of chemotherapeutic agents |
| US6537579B1 (en) | 1993-02-22 | 2003-03-25 | American Bioscience, Inc. | Compositions and methods for administration of pharmacologically active compounds |
| WO2004014871A1 (en) * | 2002-08-08 | 2004-02-19 | Amgen Inc. | Vanilloid receptor ligands and their use in treatments |
| WO2004020434A1 (ja) * | 2002-08-30 | 2004-03-11 | Eisai Co., Ltd. | 含窒素芳香環誘導体 |
| WO2007109783A2 (en) * | 2006-03-23 | 2007-09-27 | Janssen Pharmaceutica, N.V. | Substituted pyrimidine kinase inhibitors |
| EP2154967B9 (en) * | 2007-04-16 | 2014-07-23 | Hutchison Medipharma Enterprises Limited | Pyrimidine derivatives |
| JO3265B1 (ar) * | 2008-12-09 | 2018-09-16 | Novartis Ag | مثبطات بيريديلوكسى اندولات vegf-r2 واستخدامها لعلاج المرض |
| UY32351A (es) * | 2008-12-22 | 2010-07-30 | Astrazeneca Ab | Compuestos de pirimidinil indol para uso como inhibidores de atr |
| US8158625B2 (en) | 2009-05-27 | 2012-04-17 | Genentech, Inc. | Bicyclic indole-pyrimidine PI3K inhibitor compounds selective for P110 delta, and methods of use |
| BR112012015612A2 (pt) * | 2009-12-25 | 2016-03-15 | Mochida Pharm Co Ltd | novo derivado de 3-hidróxi-5-arilisotiazol |
| US9458137B2 (en) * | 2012-11-05 | 2016-10-04 | Nantbioscience, Inc. | Substituted indol-5-ol derivatives and their therapeutical applications |
| EP2968332A4 (en) * | 2013-03-15 | 2016-08-03 | Nantbioscience Inc | SUBSTITUTED INDOL-5-OL DERIVATIVES AND THEIR THERAPEUTIC APPLICATIONS |
| WO2014183300A1 (en) * | 2013-05-17 | 2014-11-20 | Suzhou Vivotide Biotechnologies Co., Ltd. | Vegfr tyrosine kinase inhibitors |
| WO2016137506A1 (en) * | 2015-02-27 | 2016-09-01 | Nantbioscience, Inc. | Pyrimidine derivatives as kinase inhibitors and their therapeutical applications |
-
2015
- 2015-02-27 WO PCT/US2015/018085 patent/WO2016137506A1/en active Application Filing
- 2015-02-27 BR BR112017018183A patent/BR112017018183A2/pt active Search and Examination
- 2015-02-27 EP EP15883597.5A patent/EP3261637B1/en active Active
- 2015-02-27 AU AU2015383881A patent/AU2015383881B2/en active Active
- 2015-02-27 US US15/553,890 patent/US10766879B2/en active Active
- 2015-02-27 CN CN201580078344.7A patent/CN107708690B/zh active Active
- 2015-02-27 RU RU2017133419A patent/RU2701188C2/ru active
- 2015-02-27 CA CA2977764A patent/CA2977764C/en active Active
- 2015-02-27 JP JP2017545365A patent/JP6444525B2/ja active Active
- 2015-02-27 KR KR1020177026941A patent/KR20170122782A/ko not_active Application Discontinuation
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2016
- 2016-02-29 WO PCT/US2016/020095 patent/WO2016138527A1/en active Application Filing
- 2016-02-29 JP JP2017545369A patent/JP6442071B2/ja active Active
- 2016-02-29 EP EP16756548.0A patent/EP3261638B1/en active Active
- 2016-02-29 KR KR1020177026878A patent/KR102008082B1/ko active IP Right Grant
- 2016-02-29 US US15/553,870 patent/US20180215734A1/en not_active Abandoned
- 2016-02-29 RU RU2017133448A patent/RU2718915C2/ru not_active IP Right Cessation
- 2016-02-29 AU AU2016224969A patent/AU2016224969B2/en active Active
- 2016-02-29 ES ES16756548T patent/ES2746007T3/es active Active
- 2016-02-29 CN CN201680018774.4A patent/CN107635553B/zh active Active
- 2016-02-29 CA CA2977810A patent/CA2977810A1/en not_active Abandoned
- 2016-02-29 BR BR112017018409A patent/BR112017018409A2/pt not_active Application Discontinuation
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2017
- 2017-08-24 IL IL254152A patent/IL254152B/en active IP Right Grant
- 2017-08-24 IL IL254151A patent/IL254151A0/en active IP Right Grant
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2018
- 2018-07-03 HK HK18108611.2A patent/HK1248600B/zh unknown
- 2018-07-03 HK HK18108612.1A patent/HK1248601A1/zh unknown
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