CN102197032B - 杂环pim-激酶抑制剂 - Google Patents
杂环pim-激酶抑制剂 Download PDFInfo
- Publication number
- CN102197032B CN102197032B CN200980142961.3A CN200980142961A CN102197032B CN 102197032 B CN102197032 B CN 102197032B CN 200980142961 A CN200980142961 A CN 200980142961A CN 102197032 B CN102197032 B CN 102197032B
- Authority
- CN
- China
- Prior art keywords
- amino
- pyridin
- quinazoline
- difluorophenyl
- amine
- 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.)
- Expired - Fee Related
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- 125000000623 heterocyclic group Chemical group 0.000 title description 9
- 229940043355 kinase inhibitor Drugs 0.000 title description 2
- 239000003757 phosphotransferase inhibitor Substances 0.000 title description 2
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- -1 amino, hydroxyl Chemical group 0.000 claims description 111
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 65
- 150000003839 salts Chemical class 0.000 claims description 48
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 42
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- 239000011737 fluorine Substances 0.000 claims description 25
- 229910052731 fluorine Inorganic materials 0.000 claims description 25
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 18
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- 238000002360 preparation method Methods 0.000 claims description 16
- PDLQGOYYXRNZOD-UHFFFAOYSA-N quinazolin-8-amine Chemical compound N1=CN=C2C(N)=CC=CC2=C1 PDLQGOYYXRNZOD-UHFFFAOYSA-N 0.000 claims description 16
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- ODHWZXUUXOFUQZ-WBVHZDCISA-N n-[4-[(3s,5r)-3-amino-5-methylpiperidin-1-yl]pyridin-3-yl]-2-(2,6-difluorophenyl)quinazolin-8-amine Chemical compound C1[C@H](C)C[C@H](N)CN1C1=CC=NC=C1NC1=CC=CC2=CN=C(C=3C(=CC=CC=3F)F)N=C12 ODHWZXUUXOFUQZ-WBVHZDCISA-N 0.000 claims description 5
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- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 1
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- ZDPHROOEEOARMN-UHFFFAOYSA-M undecanoate Chemical compound CCCCCCCCCCC([O-])=O ZDPHROOEEOARMN-UHFFFAOYSA-M 0.000 description 1
- 125000002948 undecyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
Classifications
-
- 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
- C07D401/12—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 chain containing hetero atoms as chain links
-
- 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
- A61K31/517—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
-
- 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
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
-
- 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
- A61P37/08—Antiallergic agents
-
- 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
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Immunology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pulmonology (AREA)
- Oncology (AREA)
- Hematology (AREA)
- Epidemiology (AREA)
- Transplantation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US9366408P | 2008-09-02 | 2008-09-02 | |
| US61/093,664 | 2008-09-02 | ||
| PCT/EP2009/061188 WO2010026122A1 (en) | 2008-09-02 | 2009-08-31 | Heterocyclic pim-kinase inhibitors |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN102197032A CN102197032A (zh) | 2011-09-21 |
| CN102197032B true CN102197032B (zh) | 2014-07-23 |
Family
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Family Applications (1)
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| CN200980142961.3A Expired - Fee Related CN102197032B (zh) | 2008-09-02 | 2009-08-31 | 杂环pim-激酶抑制剂 |
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| EP (1) | EP2344473B1 (enExample) |
| JP (1) | JP5584215B2 (enExample) |
| KR (1) | KR20110056399A (enExample) |
| CN (1) | CN102197032B (enExample) |
| AU (1) | AU2009289317A1 (enExample) |
| BR (1) | BRPI0918846A2 (enExample) |
| CA (1) | CA2735782A1 (enExample) |
| EA (1) | EA201100427A1 (enExample) |
| MX (1) | MX2011002362A (enExample) |
| WO (1) | WO2010026122A1 (enExample) |
Families Citing this family (37)
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| DK3184526T3 (en) | 2005-12-13 | 2019-01-14 | Incyte Holdings Corp | PYRROLO [2,3-D] PYRIMIDINE DERIVATIVES AS A JANUS-KINASE INHIBITOR |
| EP2740731B1 (en) | 2007-06-13 | 2016-03-23 | Incyte Holdings Corporation | Crystalline salts of the janus kinase inhibitor (r)-3-(4-(7h-pyrrolo[2,3-d]pyrimidin-4-yl)-1h-pyrazol-1-yl)-3-cyclopentylpropanenitrile |
| ES2487542T3 (es) | 2009-05-22 | 2014-08-21 | Incyte Corporation | Derivados de N-(hetero)aril-pirrolidina de pirazol-4-il-pirrolo[2,3-d]pirimidinas y pirrol-3-il-pirrolo[2,3-d]pirimidinas como inhibidores de cinasas Janus |
| WO2010135621A1 (en) | 2009-05-22 | 2010-11-25 | Incyte Corporation | 3-[4-(7h-pyrrolo[2,3-d]pyrimidin-4-yl)-1h-pyrazol-1-yl]octane- or heptane-nitrile as jak inhibitors |
| WO2011028685A1 (en) | 2009-09-01 | 2011-03-10 | Incyte Corporation | Heterocyclic derivatives of pyrazol-4-yl-pyrrolo[2,3-d]pyrimidines as janus kinase inhibitors |
| SMT201800137T1 (it) | 2010-03-10 | 2018-07-17 | Incyte Holdings Corp | Derivati di piperidin-4-il azetidina come inibitori di jak1 |
| PH12012502296B1 (en) | 2010-05-21 | 2017-10-06 | Incyte Holdings Corp | Topical formulation for a jak inhibitor |
| ES2536415T3 (es) | 2010-11-19 | 2015-05-25 | Incyte Corporation | Pirrolopiridinas y pirrolopirimidinas sustituidas heterocíclicas como inhibidores de JAK |
| SG190839A1 (en) | 2010-11-19 | 2013-07-31 | Incyte Corp | Cyclobutyl substituted pyrrolopyridine and pyrrolopyrimidine derivatives as jak inhibitors |
| WO2012177606A1 (en) | 2011-06-20 | 2012-12-27 | Incyte Corporation | Azetidinyl phenyl, pyridyl or pyrazinyl carboxamide derivatives as jak inhibitors |
| ES2834093T3 (es) | 2011-07-21 | 2021-06-16 | Sumitomo Dainippon Pharma Oncology Inc | Inhibidores de proteína quinasa heterocíclicos |
| TW201313721A (zh) | 2011-08-18 | 2013-04-01 | Incyte Corp | 作為ｊａｋ抑制劑之環己基氮雜環丁烷衍生物 |
| UA111854C2 (uk) | 2011-09-07 | 2016-06-24 | Інсайт Холдінгс Корпорейшн | Способи і проміжні сполуки для отримання інгібіторів jak |
| WO2013173720A1 (en) | 2012-05-18 | 2013-11-21 | Incyte Corporation | Piperidinylcyclobutyl substituted pyrrolopyridine and pyrrolopyrimidine derivatives as jak inhibitors |
| PE20151157A1 (es) | 2012-11-15 | 2015-08-19 | Incyte Corp | Formas de dosificacion de ruxolitinib de liberacion sostenida |
| EP2943485B1 (en) | 2013-01-14 | 2017-09-20 | Incyte Holdings Corporation | Bicyclic aromatic carboxamide compounds useful as pim kinase inhibitors |
| HUE050215T2 (hu) | 2013-01-15 | 2020-11-30 | Incyte Holdings Corp | Pim kináz inhibitorokként hasznos tiazolkarboxamid és piridinkarboxamid vegyületek |
| LT3489239T (lt) | 2013-03-06 | 2022-03-10 | Incyte Holdings Corporation | Jak inhibitoriaus gamybos būdai ir tarpiniai junginiai |
| UA120499C2 (uk) | 2013-08-07 | 2019-12-26 | Інсайт Корпорейшн | Лікування захворювань із застосуванням лікарських форм з уповільненим вивільненням для інгібітора jak1 |
| TW201605866A (zh) | 2013-08-23 | 2016-02-16 | 英塞特公司 | 可用作ｐｉｍ激酶抑制劑之呋喃并－及噻吩并－吡啶甲醯胺化合物 |
| WO2015184305A1 (en) | 2014-05-30 | 2015-12-03 | Incyte Corporation | TREATMENT OF CHRONIC NEUTROPHILIC LEUKEMIA (CNL) AND ATYPICAL CHRONIC MYELOID LEUKEMIA (aCML) BY INHIBITORS OF JAK1 |
| US9580418B2 (en) | 2014-07-14 | 2017-02-28 | Incyte Corporation | Bicyclic aromatic carboxamide compounds useful as Pim kinase inhibitors |
| WO2016010897A1 (en) | 2014-07-14 | 2016-01-21 | Incyte Corporation | Bicyclic heteroaromatic carboxamide compounds useful as pim kinase inhibitors |
| US9540347B2 (en) | 2015-05-29 | 2017-01-10 | Incyte Corporation | Pyridineamine compounds useful as Pim kinase inhibitors |
| TWI734699B (zh) | 2015-09-09 | 2021-08-01 | 美商英塞特公司 | Ｐｉｍ激酶抑制劑之鹽 |
| WO2017059251A1 (en) | 2015-10-02 | 2017-04-06 | Incyte Corporation | Heterocyclic compounds useful as pim kinase inhibitors |
| CN108373476B (zh) * | 2017-01-13 | 2021-06-01 | 成都地奥制药集团有限公司 | 一种激酶抑制剂及其制备和应用 |
| WO2019113487A1 (en) | 2017-12-08 | 2019-06-13 | Incyte Corporation | Low dose combination therapy for treatment of myeloproliferative neoplasms |
| IL276302B2 (en) | 2018-01-30 | 2023-11-01 | Incyte Corp | Procedures for preparing [1-(3-fluoro-2-(trifluoromethyl(isonicotinyl}piperidine-4-one) |
| SMT202400306T1 (it) | 2018-03-30 | 2024-09-16 | Incyte Corp | Trattamento dell'idrosadenite suppurativa utilizzando inibitori di jak. |
| CA3095580A1 (en) | 2018-04-13 | 2019-10-17 | Sumitomo Dainippon Pharma Oncology, Inc. | Pim kinase inhibitors for treatment of myeloproliferative neoplasms and fibrosis associated with cancer |
| CN109369513B (zh) * | 2018-11-20 | 2020-08-25 | 都创(上海)医药科技有限公司 | 一种fbdd常用分子片段的制备方法 |
| CN111362922A (zh) * | 2018-12-26 | 2020-07-03 | 上海喆邺生物科技有限公司 | 2,4-二氨基嘧啶衍生物及其用途 |
| HUE072069T2 (hu) | 2019-02-12 | 2025-10-28 | Sumitomo Pharma America Inc | 2-((1R,4R)-4-((3-(3-(trifluormetil)fenil)imidazo[1,2- b]piridazin-6-il)amino)ciklohexil)propán-2-ol sósavas sójának kristályos formája |
| US11833155B2 (en) | 2020-06-03 | 2023-12-05 | Incyte Corporation | Combination therapy for treatment of myeloproliferative neoplasms |
| TW202237119A (zh) | 2020-12-10 | 2022-10-01 | 美商住友製藥腫瘤公司 | Ａｌｋ﹘５抑制劑和彼之用途 |
| AU2023372386A1 (en) | 2022-10-31 | 2025-05-08 | Sumitomo Pharma America, Inc. | Pim1 inhibitor for treating myeloproliferative neoplasms |
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| US6184226B1 (en) * | 1998-08-28 | 2001-02-06 | Scios Inc. | Quinazoline derivatives as inhibitors of P-38 α |
| GB0226724D0 (en) | 2002-11-15 | 2002-12-24 | Merck Sharp & Dohme | Therapeutic agents |
| WO2004081000A1 (en) * | 2003-03-10 | 2004-09-23 | Astrazeneca Ab | Quinazoline derivatives |
| WO2004108707A1 (en) * | 2003-06-05 | 2004-12-16 | Astrazeneca Ab | Pyridazinil quinazoline derivatives for use in the treatment of tumours |
| WO2005028467A1 (en) | 2003-09-15 | 2005-03-31 | Anadys Pharmaceuticals, Inc. | Antibacterial 3,5-diaminopiperidine-substitute aromatic and heteroaromatic compounds |
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| WO2007027729A1 (en) | 2005-08-29 | 2007-03-08 | Vertex Pharmaceuticals Incorporated | 3, 5-disubstituted pyrid-2-ones useful as inhibitors of tec family of non-receptor tyrosine kinases |
| US7989461B2 (en) | 2005-12-23 | 2011-08-02 | Amgen Inc. | Substituted quinazolinamine compounds for the treatment of cancer |
| ES2558706T3 (es) * | 2006-06-13 | 2016-02-08 | Wyeth Llc | 3-cianopiridinas sustituidas como inhibidores de proteína cinasa |
| PT2061765E (pt) * | 2006-09-01 | 2015-02-06 | Senhwa Biosciences Inc | Moduladores de serina-treonina-proteína-quinase e de parp |
| WO2008153947A2 (en) * | 2007-06-07 | 2008-12-18 | Amgen Inc. | Heterocyclic compounds as raf kinase modulators |
-
2009
- 2009-08-31 CA CA2735782A patent/CA2735782A1/en not_active Abandoned
- 2009-08-31 US US13/061,009 patent/US8759338B2/en not_active Expired - Fee Related
- 2009-08-31 CN CN200980142961.3A patent/CN102197032B/zh not_active Expired - Fee Related
- 2009-08-31 WO PCT/EP2009/061188 patent/WO2010026122A1/en not_active Ceased
- 2009-08-31 EP EP09782379.3A patent/EP2344473B1/en not_active Not-in-force
- 2009-08-31 MX MX2011002362A patent/MX2011002362A/es not_active Application Discontinuation
- 2009-08-31 JP JP2011524404A patent/JP5584215B2/ja not_active Expired - Fee Related
- 2009-08-31 AU AU2009289317A patent/AU2009289317A1/en not_active Abandoned
- 2009-08-31 KR KR1020117007561A patent/KR20110056399A/ko not_active Withdrawn
- 2009-08-31 EA EA201100427A patent/EA201100427A1/ru unknown
- 2009-08-31 BR BRPI0918846A patent/BRPI0918846A2/pt not_active IP Right Cessation
Also Published As
| Publication number | Publication date |
|---|---|
| MX2011002362A (es) | 2011-04-04 |
| US8759338B2 (en) | 2014-06-24 |
| KR20110056399A (ko) | 2011-05-27 |
| EP2344473A1 (en) | 2011-07-20 |
| WO2010026122A1 (en) | 2010-03-11 |
| CA2735782A1 (en) | 2010-03-11 |
| US20110195956A1 (en) | 2011-08-11 |
| JP2012501313A (ja) | 2012-01-19 |
| EP2344473B1 (en) | 2014-04-16 |
| JP5584215B2 (ja) | 2014-09-03 |
| CN102197032A (zh) | 2011-09-21 |
| EA201100427A1 (ru) | 2011-10-31 |
| BRPI0918846A2 (pt) | 2019-09-24 |
| AU2009289317A1 (en) | 2010-03-11 |
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