CA2704052C - Polycyclic aryl substituted triazoles and polycyclic heteroaryl substituted triazoles useful as axl inhibitors - Google Patents
Polycyclic aryl substituted triazoles and polycyclic heteroaryl substituted triazoles useful as axl inhibitors Download PDFInfo
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- CA2704052C CA2704052C CA2704052A CA2704052A CA2704052C CA 2704052 C CA2704052 C CA 2704052C CA 2704052 A CA2704052 A CA 2704052A CA 2704052 A CA2704052 A CA 2704052A CA 2704052 C CA2704052 C CA 2704052C
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- optionally substituted
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- heteroaryl
- independently
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- 150000003852 triazoles Chemical class 0.000 title abstract description 13
- 239000003112 inhibitor Substances 0.000 title description 5
- 150000001875 compounds Chemical class 0.000 claims abstract description 414
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 180
- 239000001257 hydrogen Substances 0.000 claims abstract description 137
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 137
- 125000003710 aryl alkyl group Chemical group 0.000 claims abstract description 98
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 45
- 201000010099 disease Diseases 0.000 claims abstract description 44
- 239000008194 pharmaceutical composition Chemical class 0.000 claims abstract description 37
- 125000003118 aryl group Chemical group 0.000 claims abstract description 36
- 230000003197 catalytic effect Effects 0.000 claims abstract description 11
- 229910052799 carbon Inorganic materials 0.000 claims description 274
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 215
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 197
- 125000002947 alkylene group Chemical group 0.000 claims description 194
- 125000001072 heteroaryl group Chemical group 0.000 claims description 164
- 125000000623 heterocyclic group Chemical group 0.000 claims description 162
- 125000001188 haloalkyl group Chemical group 0.000 claims description 159
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 151
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 145
- 229910052757 nitrogen Inorganic materials 0.000 claims description 140
- 125000004450 alkenylene group Chemical group 0.000 claims description 135
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 131
- 125000004419 alkynylene group Chemical group 0.000 claims description 127
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 123
- 125000001424 substituent group Chemical group 0.000 claims description 123
- 125000004043 oxo group Chemical group O=* 0.000 claims description 112
- 125000000464 thioxo group Chemical group S=* 0.000 claims description 112
- 125000004446 heteroarylalkyl group Chemical group 0.000 claims description 107
- 125000004415 heterocyclylalkyl group Chemical group 0.000 claims description 101
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 95
- 125000003107 substituted aryl group Chemical group 0.000 claims description 86
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- 125000005346 substituted cycloalkyl group Chemical group 0.000 claims description 59
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- 125000000262 haloalkenyl group Chemical group 0.000 claims description 22
- 125000000304 alkynyl group Chemical group 0.000 claims description 20
- 125000005356 cycloalkylalkenyl group Chemical group 0.000 claims description 19
- 125000005357 cycloalkylalkynyl group Chemical group 0.000 claims description 19
- 125000000232 haloalkynyl group Chemical group 0.000 claims description 19
- 125000004447 heteroarylalkenyl group Chemical group 0.000 claims description 19
- 125000005312 heteroarylalkynyl group Chemical group 0.000 claims description 19
- 125000004449 heterocyclylalkenyl group Chemical group 0.000 claims description 19
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- RXXAPMNPVYZCAQ-UHFFFAOYSA-N 1-(3,4-diazatricyclo[9.4.0.02,7]pentadeca-1(15),2,4,6,11,13-hexaen-5-yl)-3-N-(7-methoxyimino-6,8,9,10-tetrahydro-5H-cycloocta[b]pyridin-3-yl)-1,2,4-triazole-3,5-diamine Chemical compound N1=NC(=CC2=C1C1=C(CCC2)C=CC=C1)N1N=C(N=C1N)NC=1C=C2C(=NC1)CCCC(CC2)=NOC RXXAPMNPVYZCAQ-UHFFFAOYSA-N 0.000 claims 1
- VVCCJGLZUWZWLB-UHFFFAOYSA-N 1-(5,6,7,8,9,10-hexahydrocycloocta[d]pyrimidin-4-yl)-3-n-spiro[1,3-dioxolane-2,7'-5,6,8,9-tetrahydrobenzo[7]annulene]-3'-yl-1,2,4-triazole-3,5-diamine Chemical compound N=1N(C=2C=3CCCCCCC=3N=CN=2)C(N)=NC=1NC(C=C1CC2)=CC=C1CCC12OCCO1 VVCCJGLZUWZWLB-UHFFFAOYSA-N 0.000 claims 1
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- OEXRFIVNXFUTOS-UHFFFAOYSA-N 1-(6,7-dihydro-5h-benzo[2,3]cyclohepta[2,4-d]pyridazin-3-yl)-3-n-(7-pyrrolidin-1-yl-5,6,7,8,9,10-hexahydrocycloocta[b]pyridin-3-yl)-1,2,4-triazole-3,5-diamine Chemical compound N=1N(C=2N=NC=3C4=CC=CC=C4CCCC=3C=2)C(N)=NC=1NC(C=C1CC2)=CN=C1CCCC2N1CCCC1 OEXRFIVNXFUTOS-UHFFFAOYSA-N 0.000 claims 1
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- 229960000281 trometamol Drugs 0.000 description 1
- 210000004881 tumor cell Anatomy 0.000 description 1
- 229960002703 undecylenic acid Drugs 0.000 description 1
- 230000003827 upregulation Effects 0.000 description 1
- 239000012646 vaccine adjuvant Substances 0.000 description 1
- 229940124931 vaccine adjuvant Drugs 0.000 description 1
- 238000010200 validation analysis Methods 0.000 description 1
- 210000005166 vasculature Anatomy 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 230000009385 viral infection Effects 0.000 description 1
- 239000003643 water by type Substances 0.000 description 1
- 239000008215 water for injection Substances 0.000 description 1
- 230000029663 wound healing Effects 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
Classifications
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- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
- A61K31/4439—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
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- C07D471/08—Bridged systems
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- 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
- C07D471/12—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 three hetero rings
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- C07D491/12—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains three hetero rings
- C07D491/14—Ortho-condensed systems
Landscapes
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US98310707P | 2007-10-26 | 2007-10-26 | |
| US60/983,107 | 2007-10-26 | ||
| PCT/US2007/089178 WO2009054864A1 (en) | 2007-10-26 | 2007-12-29 | Polycyclic aryl substituted triazoles and polycyclic heteroaryl substituted triazoles useful as axl inhibitors |
Publications (2)
| Publication Number | Publication Date |
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| CA2704052A1 CA2704052A1 (en) | 2009-04-30 |
| CA2704052C true CA2704052C (en) | 2015-04-21 |
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| CA2704052A Active CA2704052C (en) | 2007-10-26 | 2007-12-29 | Polycyclic aryl substituted triazoles and polycyclic heteroaryl substituted triazoles useful as axl inhibitors |
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| EP (1) | EP2205592B1 (cg-RX-API-DMAC7.html) |
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| ES (1) | ES2424259T3 (cg-RX-API-DMAC7.html) |
| SI (1) | SI2205592T1 (cg-RX-API-DMAC7.html) |
| WO (1) | WO2009054864A1 (cg-RX-API-DMAC7.html) |
Families Citing this family (89)
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| JP2009507080A (ja) * | 2005-09-07 | 2009-02-19 | リゲル ファーマシューティカルズ,インコーポレーテッド | Axl阻害剤として有用なトリアゾール誘導体 |
| ES2607065T3 (es) | 2006-12-29 | 2017-03-29 | Rigel Pharmaceuticals, Inc. | Triazoles N3-heteroaril sustituidos y triazoles N5-heteroaril sustituidos útiles como inhibidores de axl |
| AU2007342007A1 (en) | 2006-12-29 | 2008-07-10 | Rigel Pharmaceuticals, Inc. | Substituted triazoles useful as Axl inhibitors |
| US8012965B2 (en) | 2006-12-29 | 2011-09-06 | Rigel Pharmaceuticals, Inc. | Bridged bicyclic aryl and bridged bicyclic heteroaryl substituted triazoles useful as axl inhibitors |
| AU2007341937B2 (en) * | 2006-12-29 | 2013-07-11 | Rigel Pharmaceuticals, Inc. | Polycyclic heteroaryl substituted triazoles useful as Axl inhibitors |
| ES2406930T3 (es) * | 2006-12-29 | 2013-06-10 | Rigel Pharmaceuticals, Inc. | Triazoles sustituidos con arilo bicíclico y heteroarilo bicíclico útiles como inhibidores de AXL |
| US7935693B2 (en) * | 2007-10-26 | 2011-05-03 | Rigel Pharmaceuticals, Inc. | Polycyclic aryl substituted triazoles and polycyclic heteroaryl substituted triazoles useful as Axl inhibitors |
| HRP20170317T1 (hr) | 2008-02-15 | 2017-04-21 | Rigel Pharmaceuticals, Inc. | Spojevi pirimidin-2-amina i njihova uporaba kao inhibitora jak kinaza |
| ES2537480T3 (es) | 2008-07-09 | 2015-06-08 | Rigel Pharmaceuticals, Inc. | Triazoles sustituidos con heteroarilo policíclicos útiles como inhibidores de Axl |
| HRP20130045T1 (hr) * | 2008-07-09 | 2013-02-28 | Rigel Pharmaceuticals, Inc. | Premošteni bicikliäśki heteroaril supstituirani triazoli koji su korisni kao axl inhibitori |
| JP4644273B2 (ja) * | 2008-07-15 | 2011-03-02 | 本田技研工業株式会社 | 車両周辺監視装置 |
| JP5858789B2 (ja) * | 2009-01-16 | 2016-02-10 | ライジェル ファーマシューティカルズ, インコーポレイテッド | 転移性癌の予防、治療、または管理のための併用療法に用いるためのaxl阻害薬 |
| JP6006241B2 (ja) | 2012-01-31 | 2016-10-12 | 第一三共株式会社 | ピリドン誘導体 |
| WO2013162061A1 (ja) * | 2012-04-26 | 2013-10-31 | 第一三共株式会社 | 二環性ピリミジン化合物 |
| CA2879542A1 (en) | 2012-07-25 | 2014-01-30 | Salk Institute For Biological Studies | Regulating the interaction between tam ligands and lipid membranes with exposed phosphatidylserine |
| CN105916506B (zh) | 2013-11-20 | 2020-01-07 | 圣诺康生命科学公司 | 作为tam家族激酶抑制剂的喹唑啉衍生物 |
| EP3074390B1 (en) | 2013-11-27 | 2020-07-08 | SignalChem Lifesciences Corporation | Aminopyridine derivatives as tam family kinase inhibitors |
| TWI723572B (zh) * | 2014-07-07 | 2021-04-01 | 日商第一三共股份有限公司 | 具有四氫吡喃基甲基之吡啶酮衍生物及其用途 |
| US9840503B2 (en) | 2015-05-11 | 2017-12-12 | Incyte Corporation | Heterocyclic compounds and uses thereof |
| GB201509338D0 (en) | 2015-05-29 | 2015-07-15 | Bergenbio As | Combination therapy |
| WO2017027717A1 (en) | 2015-08-12 | 2017-02-16 | Incyte Corporation | Bicyclic fused pyrimidine compounds as tam inhibitors |
| US10053465B2 (en) | 2015-08-26 | 2018-08-21 | Incyte Corporation | Pyrrolopyrimidine derivatives as TAM inhibitors |
| US10947598B2 (en) | 2015-09-29 | 2021-03-16 | Inserm (Institut National De La Sante Et De La Recherche Medicale) | Methods for determining the metabolic status of lymphomas |
| EP3400443B1 (en) | 2016-01-04 | 2020-09-16 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Use of pd-1 and tim-3 as a measure for cd8+ cells in predicting and treating renal cell carcinoma |
| WO2017146236A1 (ja) | 2016-02-26 | 2017-08-31 | 小野薬品工業株式会社 | Axl阻害剤と免疫チェックポイント阻害剤とを組み合わせて投与することを特徴とする癌治療のための医薬 |
| KR102558066B1 (ko) | 2016-03-28 | 2023-07-25 | 인사이트 코포레이션 | Tam 억제제로서 피롤로트리아진 화합물 |
| CA3051851A1 (en) * | 2017-01-26 | 2018-08-02 | Semper Fortis Solutions, LLC | Multiple single levels of security (msls) in a multi-tenant cloud |
| EP3600427A1 (en) | 2017-03-24 | 2020-02-05 | INSERM - Institut National de la Santé et de la Recherche Médicale | Methods and compositions for treating melanoma |
| WO2019039525A1 (ja) | 2017-08-23 | 2019-02-28 | 小野薬品工業株式会社 | Axl阻害剤を有効成分として含むがん治療剤 |
| IL273579B2 (en) | 2017-09-27 | 2025-10-01 | Incyte Corp | Salts of pyrrolizidine derivatives used as Tm inhibitors. |
| WO2019074116A1 (ja) | 2017-10-13 | 2019-04-18 | 小野薬品工業株式会社 | Axl阻害剤を有効成分として含む固形がん治療剤 |
| EP3735590A1 (en) | 2018-01-04 | 2020-11-11 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods and compositions for treating melanoma resistant |
| WO2019162325A1 (en) | 2018-02-21 | 2019-08-29 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Use of sk1 as biomarker for predicting response to immunecheckpoint inhibitors |
| HRP20250676T1 (hr) | 2018-06-29 | 2025-08-01 | Incyte Corporation | Formulacije inhibitora axl/mer |
| EP3883964A1 (en) | 2018-11-20 | 2021-09-29 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Bispecific antibody targeting transferrin receptor 1 and soluble antigen |
| WO2020104479A1 (en) | 2018-11-20 | 2020-05-28 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods and compositions for treating cancers and resistant cancers with anti transferrin receptor 1 antibodies |
| WO2020115261A1 (en) | 2018-12-07 | 2020-06-11 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods and compositions for treating melanoma |
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| WO2020127411A1 (en) | 2018-12-19 | 2020-06-25 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods and compositions for treating cancers by immuno-modulation using antibodies against cathespin-d |
| WO2020127885A1 (en) | 2018-12-21 | 2020-06-25 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Compositions for treating cancers and resistant cancers |
| EP3918332B1 (en) | 2019-01-30 | 2025-03-19 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods and compositions for identifying whether a subject suffering from a cancer will achieve a response with an immune-checkpoint inhibitor |
| WO2020161083A1 (en) | 2019-02-04 | 2020-08-13 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods and compositions for modulating blood-brain barrier |
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| BR112021018168B1 (pt) | 2019-03-21 | 2023-11-28 | Onxeo | Composição farmacêutica, combinação e kit compreendendo uma molécula dbait e um inibidor de quinase para o tratamento de câncer |
| EP3963109A1 (en) | 2019-04-30 | 2022-03-09 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods and compositions for treating melanoma |
| GB201912059D0 (en) | 2019-08-22 | 2019-10-09 | Bergenbio As | Combaination therapy of a patient subgroup |
| WO2021048292A1 (en) | 2019-09-11 | 2021-03-18 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods and compositions for treating melanoma |
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| US20240122938A1 (en) | 2019-10-29 | 2024-04-18 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods and compositions for treating uveal melanoma |
| KR20220098759A (ko) | 2019-11-08 | 2022-07-12 | 인쎄름 (엥스띠뛰 나씨오날 드 라 쌍떼 에 드 라 흐쉐르슈 메디깔) | 키나제 억제제에 대해 내성을 획득한 암의 치료 방법 |
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Family Cites Families (27)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB1403866A (en) | 1971-12-06 | 1975-08-28 | Wyeth John & Brother Ltd | Derivatives of 3-amino-1,2,4-triazoles |
| EP0710654A4 (en) | 1993-07-23 | 1996-08-28 | Green Cross Corp | TRIAZOLE DERIVATIVE AND ITS PHARMACEUTICAL USE |
| GB9918180D0 (en) | 1999-08-02 | 1999-10-06 | Smithkline Beecham Plc | Novel compositions |
| BR0116792A (pt) * | 2000-12-22 | 2004-02-17 | Ortho Mcneil Pharm Inc | Derivados de diamina de triazol substituìdos como inibidores de quinase |
| TWI335221B (en) | 2001-09-27 | 2011-01-01 | Alcon Inc | Inhibtors of glycogen synthase kinase-3 (gsk-3) for treating glaucoma |
| BR0309688A (pt) | 2002-05-03 | 2005-02-22 | Janssen Pharmaceutica Nv | Microemulsões poliméricas |
| AU2003252395A1 (en) | 2002-08-06 | 2004-03-11 | Toray Industries, Inc. | Remedy or preventive for kidney disease and method of diagnosing kidney disease |
| WO2004039955A2 (en) | 2002-10-29 | 2004-05-13 | Rigel Pharmaceuticals, Inc. | Modulators of angiogenesis and tumorigenesis |
| TWI335913B (en) | 2002-11-15 | 2011-01-11 | Vertex Pharma | Diaminotriazoles useful as inhibitors of protein kinases |
| PE20050338A1 (es) | 2003-08-06 | 2005-05-16 | Vertex Pharma | Compuestos de aminotriazoles como inhibidores de proteina quinasas |
| US20060100259A1 (en) | 2004-02-11 | 2006-05-11 | Palmer David C | Process for the preparation of substituted triazole compounds |
| MX2007001727A (es) * | 2004-08-13 | 2007-04-20 | Genentech Inc | Compuestos a base de 2-amido-tiazol que exhiben actividad inhibidora de enzima que utiliza atp y composiciones y usos de los mismos. |
| US7329652B2 (en) * | 2004-09-17 | 2008-02-12 | Vertex Pharamaceuticals Incorporated | Diaminotriazole compounds useful as protein kinase inhibitors |
| JP2009507080A (ja) * | 2005-09-07 | 2009-02-19 | リゲル ファーマシューティカルズ,インコーポレーテッド | Axl阻害剤として有用なトリアゾール誘導体 |
| US8097630B2 (en) | 2006-10-10 | 2012-01-17 | Rigel Pharmaceuticals, Inc. | Pinane-substituted pyrimidinediamine derivatives useful as Axl inhibitors |
| US7879856B2 (en) | 2006-12-22 | 2011-02-01 | Rigel Pharmaceuticals, Inc. | Diaminothiazoles useful as Axl inhibitors |
| ES2607065T3 (es) | 2006-12-29 | 2017-03-29 | Rigel Pharmaceuticals, Inc. | Triazoles N3-heteroaril sustituidos y triazoles N5-heteroaril sustituidos útiles como inhibidores de axl |
| AU2007342007A1 (en) * | 2006-12-29 | 2008-07-10 | Rigel Pharmaceuticals, Inc. | Substituted triazoles useful as Axl inhibitors |
| AU2007341937B2 (en) * | 2006-12-29 | 2013-07-11 | Rigel Pharmaceuticals, Inc. | Polycyclic heteroaryl substituted triazoles useful as Axl inhibitors |
| US8012965B2 (en) * | 2006-12-29 | 2011-09-06 | Rigel Pharmaceuticals, Inc. | Bridged bicyclic aryl and bridged bicyclic heteroaryl substituted triazoles useful as axl inhibitors |
| ES2406930T3 (es) | 2006-12-29 | 2013-06-10 | Rigel Pharmaceuticals, Inc. | Triazoles sustituidos con arilo bicíclico y heteroarilo bicíclico útiles como inhibidores de AXL |
| CA2690653A1 (en) | 2007-06-15 | 2008-12-24 | Irm Llc | Protein kinase inhibitors and methods for using thereof |
| US7935693B2 (en) * | 2007-10-26 | 2011-05-03 | Rigel Pharmaceuticals, Inc. | Polycyclic aryl substituted triazoles and polycyclic heteroaryl substituted triazoles useful as Axl inhibitors |
| HRP20170317T1 (hr) | 2008-02-15 | 2017-04-21 | Rigel Pharmaceuticals, Inc. | Spojevi pirimidin-2-amina i njihova uporaba kao inhibitora jak kinaza |
| HRP20130045T1 (hr) | 2008-07-09 | 2013-02-28 | Rigel Pharmaceuticals, Inc. | Premošteni bicikliäśki heteroaril supstituirani triazoli koji su korisni kao axl inhibitori |
| ES2537480T3 (es) | 2008-07-09 | 2015-06-08 | Rigel Pharmaceuticals, Inc. | Triazoles sustituidos con heteroarilo policíclicos útiles como inhibidores de Axl |
| JP5858789B2 (ja) | 2009-01-16 | 2016-02-10 | ライジェル ファーマシューティカルズ, インコーポレイテッド | 転移性癌の予防、治療、または管理のための併用療法に用いるためのaxl阻害薬 |
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| US8809364B2 (en) | 2014-08-19 |
| US20090111816A1 (en) | 2009-04-30 |
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| CA2704052A1 (en) | 2009-04-30 |
| EP2205592A1 (en) | 2010-07-14 |
| JP5635909B2 (ja) | 2014-12-03 |
| SI2205592T1 (sl) | 2013-09-30 |
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