JP5232786B2 - タンパク質キナーゼ阻害剤として有用なピラゾロ（１，５−ａ）（１，３，５）トリアジン及びピラゾロ（１，５−ａ）ピリミジン誘導体 - Google Patents
タンパク質キナーゼ阻害剤として有用なピラゾロ（１，５−ａ）（１，３，５）トリアジン及びピラゾロ（１，５−ａ）ピリミジン誘導体 Download PDFInfo
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- JP5232786B2 JP5232786B2 JP2009528344A JP2009528344A JP5232786B2 JP 5232786 B2 JP5232786 B2 JP 5232786B2 JP 2009528344 A JP2009528344 A JP 2009528344A JP 2009528344 A JP2009528344 A JP 2009528344A JP 5232786 B2 JP5232786 B2 JP 5232786B2
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- Prior art keywords
- amino
- phenyl
- pyrazolo
- diaza
- cyclotetradec
- Prior art date
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- 229940045988 antineoplastic drug protein kinase inhibitors Drugs 0.000 title description 3
- 239000003909 protein kinase inhibitor Substances 0.000 title description 3
- JUXWUYWPUDKPSD-UHFFFAOYSA-N pyrazolo[1,5-a][1,3,5]triazine Chemical compound N1=CN=CN2N=CC=C21 JUXWUYWPUDKPSD-UHFFFAOYSA-N 0.000 title description 2
- LDIJKUBTLZTFRG-UHFFFAOYSA-N pyrazolo[1,5-a]pyrimidine Chemical class N1=CC=CN2N=CC=C21 LDIJKUBTLZTFRG-UHFFFAOYSA-N 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims description 81
- -1 3-ethoxyphenyl Chemical group 0.000 claims description 37
- 206010028980 Neoplasm Diseases 0.000 claims description 12
- 239000003795 chemical substances by application Substances 0.000 claims description 11
- 125000003118 aryl group Chemical group 0.000 claims description 10
- 201000011510 cancer Diseases 0.000 claims description 10
- 201000010099 disease Diseases 0.000 claims description 10
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 10
- 125000000304 alkynyl group Chemical group 0.000 claims description 9
- 125000001072 heteroaryl group Chemical group 0.000 claims description 9
- 125000003342 alkenyl group Chemical group 0.000 claims description 8
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 7
- 125000000217 alkyl group Chemical group 0.000 claims description 6
- 208000023275 Autoimmune disease Diseases 0.000 claims description 5
- 229910052739 hydrogen Inorganic materials 0.000 claims description 5
- 239000001257 hydrogen Substances 0.000 claims description 5
- 239000008194 pharmaceutical composition Substances 0.000 claims description 5
- 125000000547 substituted alkyl group Chemical group 0.000 claims description 5
- 208000024172 Cardiovascular disease Diseases 0.000 claims description 4
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 4
- 208000031888 Mycoses Diseases 0.000 claims description 3
- 239000003814 drug Substances 0.000 claims description 3
- 230000002538 fungal effect Effects 0.000 claims description 3
- 208000015122 neurodegenerative disease Diseases 0.000 claims description 3
- 230000003612 virological effect Effects 0.000 claims description 3
- 239000003937 drug carrier Substances 0.000 claims description 2
- 125000001424 substituent group Chemical group 0.000 claims description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims 18
- 125000003545 alkoxy group Chemical group 0.000 claims 3
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims 3
- 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims 2
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims 2
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 1
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims 1
- 241000255925 Diptera Species 0.000 claims 1
- 239000004480 active ingredient Substances 0.000 claims 1
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims 1
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims 1
- 238000010276 construction Methods 0.000 claims 1
- 125000000753 cycloalkyl group Chemical group 0.000 claims 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims 1
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims 1
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 claims 1
- 125000001475 halogen functional group Chemical group 0.000 claims 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims 1
- 229940124597 therapeutic agent Drugs 0.000 claims 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 36
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 32
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- 235000019439 ethyl acetate Nutrition 0.000 description 16
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- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 11
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- 239000000203 mixture Substances 0.000 description 9
- 239000002904 solvent Substances 0.000 description 9
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- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 7
- 238000000034 method Methods 0.000 description 7
- 150000003839 salts Chemical class 0.000 description 7
- 229920006395 saturated elastomer Polymers 0.000 description 7
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- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
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- CHPCUIOLRIHPDQ-UHFFFAOYSA-N ethyl 3-[[5-chloro-3-(4-cyanobutyl)pyrazolo[1,5-a]pyrimidin-7-yl]amino]benzoate Chemical compound CCOC(=O)C1=CC=CC(NC=2N3N=CC(CCCCC#N)=C3N=C(Cl)C=2)=C1 CHPCUIOLRIHPDQ-UHFFFAOYSA-N 0.000 description 5
- 239000003112 inhibitor Substances 0.000 description 5
- NQBVKXMUGHGUIS-UHFFFAOYSA-N methyl 3-[[5-(3-aminoanilino)-3-(5-methoxy-5-oxopentyl)pyrazolo[1,5-a]pyrimidin-7-yl]amino]benzoate Chemical compound C=1C(NC=2C=C(N)C=CC=2)=NC2=C(CCCCC(=O)OC)C=NN2C=1NC1=CC=CC(C(=O)OC)=C1 NQBVKXMUGHGUIS-UHFFFAOYSA-N 0.000 description 5
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- 238000000746 purification Methods 0.000 description 5
- GADZYJKFSRPXNO-UHFFFAOYSA-N 5-(2-benzylsulfanyl-4-chloropyrazolo[1,5-a][1,3,5]triazin-8-yl)pentanenitrile Chemical compound N=1C2=C(CCCCC#N)C=NN2C(Cl)=NC=1SCC1=CC=CC=C1 GADZYJKFSRPXNO-UHFFFAOYSA-N 0.000 description 4
- RHWCUEMYQPUHEW-UHFFFAOYSA-N 5-(2-benzylsulfanyl-4-oxo-3H-pyrazolo[1,5-a][1,3,5]triazin-8-yl)pentanenitrile Chemical compound N=1C2=C(CCCCC#N)C=NN2C(O)=NC=1SCC1=CC=CC=C1 RHWCUEMYQPUHEW-UHFFFAOYSA-N 0.000 description 4
- SMXFYXHXVICNDM-UHFFFAOYSA-N 5-[2-benzylsulfanyl-4-(cyclopropylamino)pyrazolo[1,5-a][1,3,5]triazin-8-yl]pentanenitrile Chemical compound N=1C(SCC=2C=CC=CC=2)=NC2=C(CCCCC#N)C=NN2C=1NC1CC1 SMXFYXHXVICNDM-UHFFFAOYSA-N 0.000 description 4
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 4
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- C07D487/12—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 three hetero rings
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- 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
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
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- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/53—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with three nitrogens as the only ring hetero atoms, e.g. chlorazanil, melamine
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- A—HUMAN NECESSITIES
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- 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
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
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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
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
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- Chemical Kinetics & Catalysis (AREA)
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- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
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- Oncology (AREA)
- Transplantation (AREA)
- Hospice & Palliative Care (AREA)
- Psychiatry (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US84531406P | 2006-09-18 | 2006-09-18 | |
| US60/845,314 | 2006-09-18 | ||
| US11/856,476 US7517882B2 (en) | 2006-09-18 | 2007-09-17 | Protein kinase inhibitors |
| US11/856,476 | 2007-09-17 | ||
| PCT/US2007/020231 WO2008036277A1 (en) | 2006-09-18 | 2007-09-18 | Pyraz0l0(l,5-a) (1, 3, 5) triazine and pyrazolo (1, 5-a) pyrimidine derivatives useful as protein kinase inhibitors |
Publications (3)
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|---|---|
| JP2010503690A JP2010503690A (ja) | 2010-02-04 |
| JP2010503690A5 JP2010503690A5 (enExample) | 2010-11-04 |
| JP5232786B2 true JP5232786B2 (ja) | 2013-07-10 |
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| EP (1) | EP2064214B1 (enExample) |
| JP (1) | JP5232786B2 (enExample) |
| KR (1) | KR101418619B1 (enExample) |
| CN (1) | CN101522683B (enExample) |
| AU (1) | AU2007297675B2 (enExample) |
| BR (1) | BRPI0718459A2 (enExample) |
| CA (1) | CA2663791C (enExample) |
| ES (1) | ES2400450T3 (enExample) |
| TW (1) | TWI472530B (enExample) |
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| US7517882B2 (en) * | 2006-09-18 | 2009-04-14 | Polaris Group | Protein kinase inhibitors |
| WO2009126514A1 (en) * | 2008-04-07 | 2009-10-15 | Irm Llc | Compounds and compositions as kinase inhibitors |
| KR20140078710A (ko) * | 2011-09-30 | 2014-06-25 | 온코디자인 에스.에이. | 거대고리 flt3 키나제 억제제 |
| SG11201507493SA (en) * | 2013-03-15 | 2015-10-29 | Oncodesign Sa | Macrocyclic salt-inducible kinase inhibitors |
| CN103570728B (zh) * | 2013-11-12 | 2015-12-30 | 山东大学 | 一种取代吡唑并[1,5-a]嘧啶类衍生物及其制备方法与应用 |
| EP3268000B1 (en) * | 2015-03-09 | 2021-08-04 | Aurigene Discovery Technologies Limited | Pyrazolo[1,5-a][1,3,5]triazine and pyrazolo[1,5-a]pyrimidine derivatives as cdk inhibitors |
| SG11201900163PA (en) * | 2016-07-28 | 2019-02-27 | Tp Therapeutics Inc | Macrocycle kinase inhibitors |
| SI3870579T1 (sl) | 2018-10-22 | 2025-03-31 | Alumis Inc. | Inhibitorji tyk2 in njihova uporaba |
| CN113811534B (zh) * | 2019-03-11 | 2024-10-29 | 阿鲁米斯公司 | Tyk2抑制剂和其用途 |
| US11780842B2 (en) * | 2019-03-26 | 2023-10-10 | Ventyx Biosciences, Inc. | TYK2 pseudokinase ligands |
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| DE10255343B4 (de) * | 2002-11-27 | 2006-09-07 | Nad Ag | N,N-Verbrückte, Stickstoff-Substituierte Carbacyclische Indolocarbazole als Proteinkinase-Inhibitoren |
| BRPI0410563B8 (pt) | 2003-05-22 | 2021-05-25 | Nerviano Medical Sciences Srl | compostos de pirazol-quinazolina, seus processos de preparação e composições farmacêuticas |
| NZ551938A (en) * | 2004-06-02 | 2010-07-30 | Takeda Pharmaceutical | Fused heterocyclic compound |
| US7517882B2 (en) * | 2006-09-18 | 2009-04-14 | Polaris Group | Protein kinase inhibitors |
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2009
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| EP2064214B1 (en) | 2013-01-30 |
| CN101522683A (zh) | 2009-09-02 |
| CA2663791C (en) | 2015-11-03 |
| CN101522683B (zh) | 2013-02-27 |
| CA2663791A1 (en) | 2008-03-27 |
| ES2400450T3 (es) | 2013-04-10 |
| HK1135688A1 (en) | 2010-06-11 |
| BRPI0718459A2 (pt) | 2013-12-03 |
| US20080070893A1 (en) | 2008-03-20 |
| EP2064214A1 (en) | 2009-06-03 |
| TWI472530B (zh) | 2015-02-11 |
| JP2010503690A (ja) | 2010-02-04 |
| AU2007297675A1 (en) | 2008-03-27 |
| WO2008036277A1 (en) | 2008-03-27 |
| KR101418619B1 (ko) | 2014-07-14 |
| AU2007297675B2 (en) | 2012-09-20 |
| TW200837065A (en) | 2008-09-16 |
| US20090247501A1 (en) | 2009-10-01 |
| KR20090083889A (ko) | 2009-08-04 |
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