TW201940485A - 作為激酶抑制劑之胺基吡咯并三 - Google Patents
作為激酶抑制劑之胺基吡咯并三 Download PDFInfo
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- TW201940485A TW201940485A TW108102873A TW108102873A TW201940485A TW 201940485 A TW201940485 A TW 201940485A TW 108102873 A TW108102873 A TW 108102873A TW 108102873 A TW108102873 A TW 108102873A TW 201940485 A TW201940485 A TW 201940485A
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- Prior art keywords
- alkyl
- alkoxy
- haloalkyl
- phenyl
- halo
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- 229940043355 kinase inhibitor Drugs 0.000 title description 3
- 239000003757 phosphotransferase inhibitor Substances 0.000 title description 3
- VPTRWECDZZUXIF-UHFFFAOYSA-N N1=NNC2=CC=NC2=C1N Chemical class N1=NNC2=CC=NC2=C1N VPTRWECDZZUXIF-UHFFFAOYSA-N 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 234
- 101001109145 Homo sapiens Receptor-interacting serine/threonine-protein kinase 1 Proteins 0.000 claims abstract description 46
- 102100022501 Receptor-interacting serine/threonine-protein kinase 1 Human genes 0.000 claims abstract description 45
- 125000000217 alkyl group Chemical group 0.000 claims description 293
- -1 C 1-3 deuteryl Chemical group 0.000 claims description 197
- 125000003545 alkoxy group Chemical group 0.000 claims description 148
- 125000005843 halogen group Chemical group 0.000 claims description 132
- 150000003839 salts Chemical class 0.000 claims description 105
- 229910052739 hydrogen Inorganic materials 0.000 claims description 100
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 100
- 125000006583 (C1-C3) haloalkyl group Chemical group 0.000 claims description 93
- 239000001257 hydrogen Substances 0.000 claims description 88
- 125000004438 haloalkoxy group Chemical group 0.000 claims description 77
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 59
- 229910052757 nitrogen Inorganic materials 0.000 claims description 58
- 150000002431 hydrogen Chemical group 0.000 claims description 56
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 51
- 125000004076 pyridyl group Chemical group 0.000 claims description 47
- 150000001412 amines Chemical class 0.000 claims description 44
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 41
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 40
- 125000006559 (C1-C3) alkylamino group Chemical group 0.000 claims description 38
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 38
- 125000004663 dialkyl amino group Chemical group 0.000 claims description 35
- 125000001424 substituent group Chemical group 0.000 claims description 34
- 229910052799 carbon Inorganic materials 0.000 claims description 28
- 125000000623 heterocyclic group Chemical group 0.000 claims description 28
- 229910052760 oxygen Inorganic materials 0.000 claims description 28
- 125000001072 heteroaryl group Chemical group 0.000 claims description 26
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 25
- 125000003884 phenylalkyl group Chemical group 0.000 claims description 22
- 238000006467 substitution reaction Methods 0.000 claims description 22
- 125000004183 alkoxy alkyl group Chemical group 0.000 claims description 21
- 125000004429 atom Chemical group 0.000 claims description 20
- 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 claims description 18
- 125000000335 thiazolyl group Chemical group 0.000 claims description 18
- 125000001188 haloalkyl group Chemical group 0.000 claims description 17
- 230000000694 effects Effects 0.000 claims description 16
- 125000003277 amino group Chemical group 0.000 claims description 15
- 125000005842 heteroatom Chemical group 0.000 claims description 15
- 229910002091 carbon monoxide Inorganic materials 0.000 claims description 14
- 239000003814 drug Substances 0.000 claims description 14
- 229910052731 fluorine Inorganic materials 0.000 claims description 13
- 125000002883 imidazolyl group Chemical group 0.000 claims description 13
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 13
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 13
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 12
- 125000003386 piperidinyl group Chemical group 0.000 claims description 12
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 11
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 11
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 11
- 201000004681 Psoriasis Diseases 0.000 claims description 10
- 125000003342 alkenyl group Chemical group 0.000 claims description 10
- 125000000304 alkynyl group Chemical group 0.000 claims description 10
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 10
- 206010039073 rheumatoid arthritis Diseases 0.000 claims description 10
- 229910052717 sulfur Inorganic materials 0.000 claims description 10
- 125000003831 tetrazolyl group Chemical group 0.000 claims description 10
- 206010009900 Colitis ulcerative Diseases 0.000 claims description 8
- 208000011231 Crohn disease Diseases 0.000 claims description 8
- 201000006704 Ulcerative Colitis Diseases 0.000 claims description 8
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 8
- 239000003795 chemical substances by application Substances 0.000 claims description 8
- 239000003937 drug carrier Substances 0.000 claims description 8
- 125000001786 isothiazolyl group Chemical group 0.000 claims description 8
- 125000001624 naphthyl group Chemical group 0.000 claims description 8
- 125000002971 oxazolyl group Chemical group 0.000 claims description 8
- 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims description 7
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical group C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 7
- YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical group [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 claims description 7
- 208000022559 Inflammatory bowel disease Diseases 0.000 claims description 7
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 7
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 claims description 7
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 7
- 125000005347 halocycloalkyl group Chemical group 0.000 claims description 7
- 206010053219 non-alcoholic steatohepatitis Diseases 0.000 claims description 7
- 125000001715 oxadiazolyl group Chemical group 0.000 claims description 7
- 239000001301 oxygen Substances 0.000 claims description 7
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims description 7
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 claims description 7
- 125000001113 thiadiazolyl group Chemical group 0.000 claims description 7
- KRNSYSYRLQDHDK-UHFFFAOYSA-N 6,7-dihydro-5h-cyclopenta[b]pyridine Chemical compound C1=CN=C2CCCC2=C1 KRNSYSYRLQDHDK-UHFFFAOYSA-N 0.000 claims description 6
- 125000003282 alkyl amino group Chemical group 0.000 claims description 6
- 125000004103 aminoalkyl group Chemical group 0.000 claims description 6
- 125000000596 cyclohexenyl group Chemical group C1(=CCCCC1)* 0.000 claims description 6
- 229910052805 deuterium Inorganic materials 0.000 claims description 6
- 125000000842 isoxazolyl group Chemical group 0.000 claims description 6
- 238000004519 manufacturing process Methods 0.000 claims description 6
- 125000003566 oxetanyl group Chemical group 0.000 claims description 6
- 239000008194 pharmaceutical composition Substances 0.000 claims description 6
- 125000001425 triazolyl group Chemical group 0.000 claims description 6
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 5
- 125000004737 (C1-C6) haloalkoxy group Chemical group 0.000 claims description 5
- 125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 claims description 5
- 150000001335 aliphatic alkanes Chemical class 0.000 claims description 5
- 125000002393 azetidinyl group Chemical group 0.000 claims description 5
- 229910052801 chlorine Inorganic materials 0.000 claims description 5
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 5
- 125000004985 dialkyl amino alkyl group Chemical group 0.000 claims description 5
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 5
- 125000005958 tetrahydrothienyl group Chemical group 0.000 claims description 5
- 206010019280 Heart failures Diseases 0.000 claims description 4
- 125000004448 alkyl carbonyl group Chemical group 0.000 claims description 4
- 229910052794 bromium Inorganic materials 0.000 claims description 4
- 125000001475 halogen functional group Chemical group 0.000 claims description 4
- 230000002401 inhibitory effect Effects 0.000 claims description 4
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 4
- 125000002490 anilino group Chemical group [H]N(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 3
- 125000003356 phenylsulfanyl group Chemical group [*]SC1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 3
- 208000024891 symptom Diseases 0.000 claims description 3
- CXWXQJXEFPUFDZ-UHFFFAOYSA-N tetralin Chemical compound C1=CC=C2CCCCC2=C1 CXWXQJXEFPUFDZ-UHFFFAOYSA-N 0.000 claims description 3
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 2
- LVWZTYCIRDMTEY-UHFFFAOYSA-N metamizole Chemical compound O=C1C(N(CS(O)(=O)=O)C)=C(C)N(C)N1C1=CC=CC=C1 LVWZTYCIRDMTEY-UHFFFAOYSA-N 0.000 claims 2
- 102000005403 Casein Kinases Human genes 0.000 claims 1
- 108010031425 Casein Kinases Proteins 0.000 claims 1
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 claims 1
- 150000001924 cycloalkanes Chemical class 0.000 claims 1
- CTAPFRYPJLPFDF-UHFFFAOYSA-N isoxazole Chemical compound C=1C=NOC=1 CTAPFRYPJLPFDF-UHFFFAOYSA-N 0.000 claims 1
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims 1
- 238000000034 method Methods 0.000 abstract description 88
- 238000011282 treatment Methods 0.000 abstract description 25
- 230000017074 necrotic cell death Effects 0.000 abstract description 9
- 206010028851 Necrosis Diseases 0.000 abstract description 8
- 206010061218 Inflammation Diseases 0.000 abstract description 5
- 108091000080 Phosphotransferase Proteins 0.000 abstract description 5
- 230000004054 inflammatory process Effects 0.000 abstract description 5
- 102000020233 phosphotransferase Human genes 0.000 abstract description 5
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 311
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 161
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 160
- 239000000203 mixture Substances 0.000 description 129
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 123
- 239000012071 phase Substances 0.000 description 109
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 105
- 229910052796 boron Inorganic materials 0.000 description 105
- GSJBZMJUMPQGKQ-UHFFFAOYSA-N 2-methyl-2-(3,3,3-trifluoro-1-methoxy-2-methylpropyl)oxirane Chemical compound CC1(OC1)C(C(C(F)(F)F)C)OC GSJBZMJUMPQGKQ-UHFFFAOYSA-N 0.000 description 86
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- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 62
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- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 50
- 239000002585 base Substances 0.000 description 50
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- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 48
- 239000002253 acid Substances 0.000 description 48
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 45
- 239000007787 solid Substances 0.000 description 45
- 235000019439 ethyl acetate Nutrition 0.000 description 44
- 229940002612 prodrug Drugs 0.000 description 42
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- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 39
- 150000002148 esters Chemical class 0.000 description 38
- QVVWQDJCCPTPLY-RXMQYKEDSA-N (1R)-1-[2-fluoro-5-(trifluoromethoxy)phenyl]ethanamine Chemical compound FC1=C(C=C(C=C1)OC(F)(F)F)[C@@H](C)N QVVWQDJCCPTPLY-RXMQYKEDSA-N 0.000 description 35
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 34
- 239000012453 solvate Substances 0.000 description 34
- LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 34
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- 238000005481 NMR spectroscopy Methods 0.000 description 30
- 238000001023 centrifugal evaporation Methods 0.000 description 28
- 238000006243 chemical reaction Methods 0.000 description 28
- YNBADRVTZLEFNH-UHFFFAOYSA-N methyl nicotinate Chemical compound COC(=O)C1=CC=CN=C1 YNBADRVTZLEFNH-UHFFFAOYSA-N 0.000 description 28
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 27
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- 238000003818 flash chromatography Methods 0.000 description 16
- KZPYGQFFRCFCPP-UHFFFAOYSA-N 1,1'-bis(diphenylphosphino)ferrocene Chemical compound [Fe+2].C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1 KZPYGQFFRCFCPP-UHFFFAOYSA-N 0.000 description 15
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- 125000004432 carbon atom Chemical group C* 0.000 description 8
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- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 6
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 6
- 208000027866 inflammatory disease Diseases 0.000 description 6
- 239000003112 inhibitor Substances 0.000 description 6
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Classifications
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- 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
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- 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
- A61K31/53—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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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A61P17/06—Antipsoriatics
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
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- A—HUMAN NECESSITIES
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- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D519/00—Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00
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| US201862622415P | 2018-01-26 | 2018-01-26 | |
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| SG (1) | SG11202007035YA (https=) |
| TW (1) | TW201940485A (https=) |
| WO (1) | WO2019147782A1 (https=) |
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| MA47460A (fr) | 2017-02-13 | 2019-12-18 | Bristol Myers Squibb Co | Aminotriazolopyridines utilisées en tant qu'inhibiteurs de kinase |
| HUE058292T2 (hu) | 2017-10-30 | 2022-07-28 | Bristol Myers Squibb Co | Aminoimidazopiridazinok mint kináz inhibitorok |
| AU2019339355A1 (en) | 2018-09-13 | 2021-05-13 | Bristol-Myers Squibb Company | Indazole carboxamides as kinase inhibitors |
| KR102906523B1 (ko) | 2018-09-13 | 2025-12-30 | 브리스톨-마이어스 스큅 컴퍼니 | 수용체-상호작용 단백질 키나제 1 (ripk1) 억제제로서의 1h-인다졸 카르복스아미드 |
| ES2969756T3 (es) | 2019-10-03 | 2024-05-22 | Bristol Myers Squibb Co | Indazol carboxamidas como inhibidores de cinasas |
| JPWO2021157596A1 (https=) * | 2020-02-07 | 2021-08-12 | ||
| WO2022007921A1 (zh) * | 2020-07-10 | 2022-01-13 | 北京范恩柯尔生物科技有限公司 | 三嗪类化合物及其组合物和用途 |
| CN111925345B (zh) * | 2020-08-21 | 2023-09-29 | 上海科利生物医药有限公司 | 一种手性2-氨甲基四氢呋喃的制备方法 |
| AR123793A1 (es) | 2020-10-19 | 2023-01-11 | Bristol Myers Squibb Co | Compuestos de triazolopiridinilo como inhibidores de quinasas |
| JPWO2022172889A1 (https=) * | 2021-02-10 | 2022-08-18 | ||
| CN113563214B (zh) * | 2021-07-06 | 2024-02-02 | 山东鲁泰控股集团有限公司石墨烯高分子复合材料研发中心 | 一种氨基乙酸的合成方法 |
| CN113527220A (zh) * | 2021-07-26 | 2021-10-22 | 京博农化科技有限公司 | 一种脱硫丙硫菌唑异构体的合成方法 |
| CN116574053B (zh) * | 2022-06-21 | 2026-04-14 | 中国药科大学 | Ripk1激酶靶点抑制剂及其医药用途 |
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| CA2627839C (en) | 2005-11-02 | 2014-08-19 | Bayer Healthcare Ag | Pyrrolo[2,1-f] [1,2,4] triazin-4-ylamines igf-1r kinase inhibitors for the treatment of cancer and other hyperproliferative diseases |
| EP2385053B1 (en) * | 2005-11-17 | 2013-10-02 | OSI Pharmaceuticals, Inc. | Intermediates for the preparation of fused bicyclic mTOR inhibitors |
| KR101461680B1 (ko) | 2005-12-02 | 2014-11-19 | 바이엘 헬스케어 엘엘씨 | 과다-증식성 장애 및 맥관형성과 관련된 질환의 치료에유용한 치환된 4-아미노-피롤로트리아진 유도체 |
| PE20070855A1 (es) | 2005-12-02 | 2007-10-14 | Bayer Pharmaceuticals Corp | Derivados de 4-amino-pirrolotriazina sustituida como inhibidores de quinasas |
| GB2467670B (en) * | 2007-10-04 | 2012-08-01 | Intellikine Inc | Chemical entities and therapeutic uses thereof |
| EP2424368B1 (en) | 2009-04-29 | 2014-12-31 | Locus Pharmaceuticals, Inc. | Pyrrolotriazine compounds |
| TW201107329A (en) | 2009-07-30 | 2011-03-01 | Oncotherapy Science Inc | Fused imidazole derivative having ttk inhibitory action |
| HRP20160967T1 (hr) | 2009-10-06 | 2016-10-07 | Millennium Pharmaceuticals, Inc. | Heterociklički spojevi korisni kao pdk1 inhibitori |
| CN102918045A (zh) | 2010-03-31 | 2013-02-06 | 百时美施贵宝公司 | 作为蛋白激酶抑制剂的取代的吡咯并三嗪 |
| WO2014047024A1 (en) | 2012-09-18 | 2014-03-27 | Bristol-Myers Squibb Company | Iap antagonists |
| WO2015054358A1 (en) | 2013-10-11 | 2015-04-16 | Bristol-Myers Squibb Company | Pyrrolotriazine kinase inhibitors |
| US10023576B2 (en) * | 2014-10-22 | 2018-07-17 | Bristol-Myers Squibb Company | Heteroaryl substituted pyrrolotriazine amine compounds as PI3K inhibitors |
| US10214537B2 (en) * | 2014-10-22 | 2019-02-26 | Bristol-Myers Squibb Company | Bicyclic heteroaryl amine compounds |
| MD3436461T2 (ro) | 2016-03-28 | 2024-05-31 | Incyte Corp | Compuși pirolotriazină ca inhibitori TAM |
| WO2018017435A1 (en) | 2016-07-22 | 2018-01-25 | Accro Bioscience Inc. | Heteroaryl compounds as inhibitors of necrosis, composition and application thereof |
| MA47460A (fr) | 2017-02-13 | 2019-12-18 | Bristol Myers Squibb Co | Aminotriazolopyridines utilisées en tant qu'inhibiteurs de kinase |
| HUE058292T2 (hu) | 2017-10-30 | 2022-07-28 | Bristol Myers Squibb Co | Aminoimidazopiridazinok mint kináz inhibitorok |
| AU2019339355A1 (en) | 2018-09-13 | 2021-05-13 | Bristol-Myers Squibb Company | Indazole carboxamides as kinase inhibitors |
| KR102906523B1 (ko) | 2018-09-13 | 2025-12-30 | 브리스톨-마이어스 스큅 컴퍼니 | 수용체-상호작용 단백질 키나제 1 (ripk1) 억제제로서의 1h-인다졸 카르복스아미드 |
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2019
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2020
- 2020-07-24 IL IL276269A patent/IL276269A/en unknown
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| IL276269A (en) | 2020-09-30 |
| CN112262139A (zh) | 2021-01-22 |
| EA202091777A1 (ru) | 2020-10-14 |
| BR112020014516A2 (pt) | 2020-12-08 |
| AU2019211382B2 (en) | 2022-06-16 |
| KR20200115550A (ko) | 2020-10-07 |
| EP3743430A1 (en) | 2020-12-02 |
| AR114186A1 (es) | 2020-07-29 |
| CA3088548A1 (en) | 2019-08-01 |
| MX2020007531A (es) | 2020-09-09 |
| CN112262139B (zh) | 2023-07-25 |
| EP3743430B1 (en) | 2023-08-02 |
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| SG11202007035YA (en) | 2020-08-28 |
| JP7307734B2 (ja) | 2023-07-12 |
| JP2021511363A (ja) | 2021-05-06 |
| US20200347071A1 (en) | 2020-11-05 |
| KR102759231B1 (ko) | 2025-01-22 |
| AU2019211382A1 (en) | 2020-09-17 |
| US11618753B2 (en) | 2023-04-04 |
| ES2959399T3 (es) | 2024-02-26 |
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