RU2742115C2 - Гетероциклические соединения в качестве ингибиторов киназы RET - Google Patents
Гетероциклические соединения в качестве ингибиторов киназы RET Download PDFInfo
- Publication number
- RU2742115C2 RU2742115C2 RU2018138471A RU2018138471A RU2742115C2 RU 2742115 C2 RU2742115 C2 RU 2742115C2 RU 2018138471 A RU2018138471 A RU 2018138471A RU 2018138471 A RU2018138471 A RU 2018138471A RU 2742115 C2 RU2742115 C2 RU 2742115C2
- Authority
- RU
- Russia
- Prior art keywords
- amino
- pyrimidin
- alkyl
- indole
- carboxamide
- Prior art date
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- 229940043355 kinase inhibitor Drugs 0.000 title abstract description 7
- 239000003757 phosphotransferase inhibitor Substances 0.000 title abstract description 7
- 150000002391 heterocyclic compounds Chemical class 0.000 title abstract 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 285
- 238000000034 method Methods 0.000 claims abstract description 76
- 101000579425 Homo sapiens Proto-oncogene tyrosine-protein kinase receptor Ret Proteins 0.000 claims abstract description 65
- 102100028286 Proto-oncogene tyrosine-protein kinase receptor Ret Human genes 0.000 claims abstract description 65
- 206010028980 Neoplasm Diseases 0.000 claims abstract description 38
- 201000011510 cancer Diseases 0.000 claims abstract description 33
- 230000002255 enzymatic effect Effects 0.000 claims abstract description 33
- 230000000694 effects Effects 0.000 claims abstract description 32
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 24
- 238000001890 transfection Methods 0.000 claims abstract description 5
- 125000000217 alkyl group Chemical group 0.000 claims description 349
- 229910052739 hydrogen Inorganic materials 0.000 claims description 208
- 239000001257 hydrogen Substances 0.000 claims description 207
- -1 (4-amino-1-tert-butylpyrazolo [3,4-d] pyrimidin-3-yl) -3-chloro-N- [1- (2-methoxyethyl) pyrazol-3-yl] -1H-indole -6-carboxamide Chemical compound 0.000 claims description 166
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 149
- 125000001424 substituent group Chemical group 0.000 claims description 114
- 229910052736 halogen Inorganic materials 0.000 claims description 108
- 150000002367 halogens Chemical class 0.000 claims description 108
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 100
- 150000003839 salts Chemical class 0.000 claims description 91
- 125000000623 heterocyclic group Chemical group 0.000 claims description 84
- 125000001188 haloalkyl group Chemical group 0.000 claims description 74
- 125000004438 haloalkoxy group Chemical group 0.000 claims description 66
- 125000003545 alkoxy group Chemical group 0.000 claims description 65
- 229910052757 nitrogen Inorganic materials 0.000 claims description 63
- 229910052760 oxygen Inorganic materials 0.000 claims description 59
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 56
- 125000005842 heteroatom Chemical group 0.000 claims description 50
- 125000003282 alkyl amino group Chemical group 0.000 claims description 45
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 42
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 37
- 125000002947 alkylene group Chemical group 0.000 claims description 34
- 229910052717 sulfur Inorganic materials 0.000 claims description 32
- 102100033177 Vascular endothelial growth factor receptor 2 Human genes 0.000 claims description 25
- 229910052799 carbon Inorganic materials 0.000 claims description 25
- 108010053099 Vascular Endothelial Growth Factor Receptor-2 Proteins 0.000 claims description 23
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 21
- 230000002401 inhibitory effect Effects 0.000 claims description 18
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 18
- 125000004103 aminoalkyl group Chemical group 0.000 claims description 14
- 238000002560 therapeutic procedure Methods 0.000 claims description 11
- 208000023356 medullary thyroid gland carcinoma Diseases 0.000 claims description 9
- 108091000080 Phosphotransferase Proteins 0.000 claims description 8
- 125000002950 monocyclic group Chemical group 0.000 claims description 8
- 230000035772 mutation Effects 0.000 claims description 8
- 208000002154 non-small cell lung carcinoma Diseases 0.000 claims description 8
- 102000020233 phosphotransferase Human genes 0.000 claims description 8
- 208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 claims description 8
- 230000004663 cell proliferation Effects 0.000 claims description 7
- 125000002971 oxazolyl group Chemical group 0.000 claims description 7
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 7
- JPKMVXLPXRWJMH-UHFFFAOYSA-N 2-(4-amino-1-tert-butylpyrazolo[3,4-d]pyrimidin-3-yl)-3-chloro-N-methyl-1H-indole-6-carboxamide Chemical compound NC1=C2C(=NC=N1)N(N=C2C=1NC2=CC(=CC=C2C=1Cl)C(=O)NC)C(C)(C)C JPKMVXLPXRWJMH-UHFFFAOYSA-N 0.000 claims description 6
- HZTDCOHZKXSXBA-UHFFFAOYSA-N NC1=C2C(=NC=N1)N(N=C2C=1NC2=CC(=CC=C2C=1)C(=O)NC)C(C)(C)C Chemical compound NC1=C2C(=NC=N1)N(N=C2C=1NC2=CC(=CC=C2C=1)C(=O)NC)C(C)(C)C HZTDCOHZKXSXBA-UHFFFAOYSA-N 0.000 claims description 5
- HKSZYXFMRVEQGF-UHFFFAOYSA-N NC1=C2C(=NC=N1)N(N=C2C=1NC2=CC(=CC=C2C=1)C(=O)NC)C(C)C Chemical compound NC1=C2C(=NC=N1)N(N=C2C=1NC2=CC(=CC=C2C=1)C(=O)NC)C(C)C HKSZYXFMRVEQGF-UHFFFAOYSA-N 0.000 claims description 5
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- OGUFXWBZNKEOCD-UHFFFAOYSA-N 2-(4-amino-1-tert-butylpyrazolo[3,4-d]pyrimidin-3-yl)-3-bromo-N-methyl-1H-indole-6-carboxamide Chemical compound NC1=C2C(=NC=N1)N(N=C2C=1NC2=CC(=CC=C2C=1Br)C(=O)NC)C(C)(C)C OGUFXWBZNKEOCD-UHFFFAOYSA-N 0.000 claims description 4
- ZLLYPULBPHUOLR-UHFFFAOYSA-N 2-(4-amino-1-tert-butylpyrazolo[3,4-d]pyrimidin-3-yl)-3-chloro-N-[1-[2-(dimethylamino)ethyl]pyrazol-3-yl]-1H-indole-6-carboxamide Chemical compound NC1=C2C(=NC=N1)N(N=C2C=1NC2=CC(=CC=C2C=1Cl)C(=O)NC1=NN(C=C1)CCN(C)C)C(C)(C)C ZLLYPULBPHUOLR-UHFFFAOYSA-N 0.000 claims description 4
- ZWNXAOSIOZQDJI-UHFFFAOYSA-N 2-(4-amino-7-propan-2-ylpyrrolo[2,3-d]pyrimidin-5-yl)-3-chloro-N-methyl-1H-indole-6-carboxamide Chemical compound NC=1C2=C(N=CN=1)N(C=C2C=1NC2=CC(=CC=C2C=1Cl)C(=O)NC)C(C)C ZWNXAOSIOZQDJI-UHFFFAOYSA-N 0.000 claims description 4
- BYSACNLCTNNHPN-UHFFFAOYSA-N 2-(4-amino-7-propan-2-ylpyrrolo[2,3-d]pyrimidin-5-yl)-N-methyl-1H-indole-6-carboxamide Chemical compound CNC(=O)c1ccc2cc([nH]c2c1)-c1cn(C(C)C)c2ncnc(N)c12 BYSACNLCTNNHPN-UHFFFAOYSA-N 0.000 claims description 4
- BQUHSWVUQMWBKQ-UHFFFAOYSA-N 2-(8-amino-3-propan-2-ylimidazo[1,5-a]pyrazin-1-yl)-3-chloro-N-methyl-1H-indole-6-carboxamide Chemical compound NC=1C=2N(C=CN=1)C(=NC=2C=1NC2=CC(=CC=C2C=1Cl)C(=O)NC)C(C)C BQUHSWVUQMWBKQ-UHFFFAOYSA-N 0.000 claims description 4
- 208000009018 Medullary thyroid cancer Diseases 0.000 claims description 4
- LRVFBQIOCULFNX-UHFFFAOYSA-N NC1=C2C(=NC=N1)N(N=C2C=1NC2=CC(=CC=C2C=1)C(=O)NC1=NN(C=C1)C)C(C)(C)C Chemical compound NC1=C2C(=NC=N1)N(N=C2C=1NC2=CC(=CC=C2C=1)C(=O)NC1=NN(C=C1)C)C(C)(C)C LRVFBQIOCULFNX-UHFFFAOYSA-N 0.000 claims description 4
- BRONVRHOEUHJIF-UHFFFAOYSA-N NC1=C2C(=NC=N1)N(N=C2C=1NC2=CC(=CC=C2C=1)NC(C)=O)C(C)(C)C Chemical compound NC1=C2C(=NC=N1)N(N=C2C=1NC2=CC(=CC=C2C=1)NC(C)=O)C(C)(C)C BRONVRHOEUHJIF-UHFFFAOYSA-N 0.000 claims description 4
- CPVUKZPQBGQJTP-UHFFFAOYSA-N NC1=NC=CC2=C1C(=NN2C(C)C)C=1NC2=CC(=CC=C2C=1)C(=O)NC Chemical compound NC1=NC=CC2=C1C(=NN2C(C)C)C=1NC2=CC(=CC=C2C=1)C(=O)NC CPVUKZPQBGQJTP-UHFFFAOYSA-N 0.000 claims description 4
- CSYZRXAIUWGVQB-UHFFFAOYSA-N NC1=NC=CC2=C1C(=NN2C(C)C)C=1NC2=CC(=CC=C2C=1Br)C(=O)NC Chemical compound NC1=NC=CC2=C1C(=NN2C(C)C)C=1NC2=CC(=CC=C2C=1Br)C(=O)NC CSYZRXAIUWGVQB-UHFFFAOYSA-N 0.000 claims description 4
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 4
- 125000001113 thiadiazolyl group Chemical group 0.000 claims description 4
- 210000004881 tumor cell Anatomy 0.000 claims description 4
- DSKWNVPCROYIQW-UHFFFAOYSA-N 2-(4-amino-1-cyclobutylpyrazolo[3,4-d]pyrimidin-3-yl)-3-chloro-N-methyl-1H-indole-6-carboxamide Chemical compound NC1=C2C(=NC=N1)N(N=C2C=1NC2=CC(=CC=C2C=1Cl)C(=O)NC)C1CCC1 DSKWNVPCROYIQW-UHFFFAOYSA-N 0.000 claims description 3
- JATHVEVHCNBUNG-UHFFFAOYSA-N 2-(4-amino-1-cyclohexylpyrazolo[3,4-d]pyrimidin-3-yl)-3-chloro-N-methyl-1H-indole-6-carboxamide Chemical compound NC1=C2C(=NC=N1)N(N=C2C=1NC2=CC(=CC=C2C=1Cl)C(=O)NC)C1CCCCC1 JATHVEVHCNBUNG-UHFFFAOYSA-N 0.000 claims description 3
- QBXTYIQNVFGQQN-UHFFFAOYSA-N 2-(4-amino-1-propan-2-ylpyrazolo[4,3-c]pyridin-3-yl)-3-chloro-N-methyl-1H-indole-6-carboxamide Chemical compound NC1=NC=CC2=C1C(=NN2C(C)C)C=1NC2=CC(=CC=C2C=1Cl)C(=O)NC QBXTYIQNVFGQQN-UHFFFAOYSA-N 0.000 claims description 3
- KHWXTXSKIPRCHN-UHFFFAOYSA-N 2-(4-amino-1-tert-butylpyrazolo[3,4-d]pyrimidin-3-yl)-1-methylindole-6-carboxylic acid Chemical compound NC1=C2C(=NC=N1)N(N=C2C=1N(C2=CC(=CC=C2C=1)C(=O)O)C)C(C)(C)C KHWXTXSKIPRCHN-UHFFFAOYSA-N 0.000 claims description 3
- XKSROQSJCOMSFN-UHFFFAOYSA-N 2-(4-amino-1-tert-butylpyrazolo[3,4-d]pyrimidin-3-yl)-3-chloro-N-(2-hydroxyethyl)-1H-indole-6-carboxamide Chemical compound NC1=C2C(=NC=N1)N(N=C2C=1NC2=CC(=CC=C2C=1Cl)C(=O)NCCO)C(C)(C)C XKSROQSJCOMSFN-UHFFFAOYSA-N 0.000 claims description 3
- GATYLOYCUAPWMB-UHFFFAOYSA-N 2-(4-amino-1-tert-butylpyrazolo[3,4-d]pyrimidin-3-yl)-3-chloro-N-(2-morpholin-4-ylethyl)-1H-indole-6-carboxamide Chemical compound NC1=C2C(=NC=N1)N(N=C2C=1NC2=CC(=CC=C2C=1Cl)C(=O)NCCN1CCOCC1)C(C)(C)C GATYLOYCUAPWMB-UHFFFAOYSA-N 0.000 claims description 3
- MJSDVPHVJFPGEB-UHFFFAOYSA-N 2-(4-amino-1-tert-butylpyrazolo[3,4-d]pyrimidin-3-yl)-3-chloro-N-(3-piperidin-1-ylpropyl)-1H-indole-6-carboxamide Chemical compound NC1=C2C(=NC=N1)N(N=C2C=1NC2=CC(=CC=C2C=1Cl)C(=O)NCCCN1CCCCC1)C(C)(C)C MJSDVPHVJFPGEB-UHFFFAOYSA-N 0.000 claims description 3
- JONUNFKBZRKJSB-UHFFFAOYSA-N 2-(4-amino-1-tert-butylpyrazolo[3,4-d]pyrimidin-3-yl)-3-chloro-N-(oxan-4-yl)-1H-indole-6-carboxamide Chemical compound NC1=C2C(=NC=N1)N(N=C2C=1NC2=CC(=CC=C2C=1Cl)C(=O)NC1CCOCC1)C(C)(C)C JONUNFKBZRKJSB-UHFFFAOYSA-N 0.000 claims description 3
- CDNJXEIHIBWNAM-UHFFFAOYSA-N 2-(4-amino-1-tert-butylpyrazolo[3,4-d]pyrimidin-3-yl)-3-chloro-N-[2-(2-morpholin-4-ylethoxy)ethyl]-1H-indole-6-carboxamide Chemical compound NC1=C2C(=NC=N1)N(N=C2C=1NC2=CC(=CC=C2C=1Cl)C(=O)NCCOCCN1CCOCC1)C(C)(C)C CDNJXEIHIBWNAM-UHFFFAOYSA-N 0.000 claims description 3
- FFPFOCJSSHPGFQ-UHFFFAOYSA-N 2-(4-amino-1-tert-butylpyrazolo[3,4-d]pyrimidin-3-yl)-3-chloro-N-cyclopropyl-1H-indole-6-carboxamide Chemical compound NC1=C2C(=NC=N1)N(N=C2C=1NC2=CC(=CC=C2C=1Cl)C(=O)NC1CC1)C(C)(C)C FFPFOCJSSHPGFQ-UHFFFAOYSA-N 0.000 claims description 3
- PYVFQLBTKLTYTG-UHFFFAOYSA-N 2-(4-amino-1-tert-butylpyrazolo[3,4-d]pyrimidin-3-yl)-3-chloro-N-ethyl-1H-indole-6-carboxamide Chemical compound NC1=C2C(=NC=N1)N(N=C2C=1NC2=CC(=CC=C2C=1Cl)C(=O)NCC)C(C)(C)C PYVFQLBTKLTYTG-UHFFFAOYSA-N 0.000 claims description 3
- SVRNPAWUQSRQDR-UHFFFAOYSA-N 2-(4-amino-1-tert-butylpyrazolo[3,4-d]pyrimidin-3-yl)-3-chloro-N-methoxy-1H-indole-6-carboxamide Chemical compound NC1=C2C(=NC=N1)N(N=C2C=1NC2=CC(=CC=C2C=1Cl)C(=O)NOC)C(C)(C)C SVRNPAWUQSRQDR-UHFFFAOYSA-N 0.000 claims description 3
- MERLQASBRDWKDQ-UHFFFAOYSA-N 2-(4-amino-1-tert-butylpyrazolo[3,4-d]pyrimidin-3-yl)-3-chloro-N-methyl-1H-pyrrolo[2,3-b]pyridine-6-carboxamide Chemical compound NC1=C2C(=NC=N1)N(N=C2C1=C(C=2C(=NC(=CC=2)C(=O)NC)N1)Cl)C(C)(C)C MERLQASBRDWKDQ-UHFFFAOYSA-N 0.000 claims description 3
- QYNGSKKAMMMUSU-UHFFFAOYSA-N 2-(4-amino-1-tert-butylpyrazolo[3,4-d]pyrimidin-3-yl)-3-chloro-N-phenyl-1H-indole-6-carboxamide Chemical compound NC1=C2C(=NC=N1)N(N=C2C=1NC2=CC(=CC=C2C=1Cl)C(=O)NC1=CC=CC=C1)C(C)(C)C QYNGSKKAMMMUSU-UHFFFAOYSA-N 0.000 claims description 3
- AHVGUCBWHJIREZ-UHFFFAOYSA-N 2-(4-amino-1-tert-butylpyrazolo[3,4-d]pyrimidin-3-yl)-3-chloro-N-propan-2-yl-1H-indole-6-carboxamide Chemical compound NC1=C2C(=NC=N1)N(N=C2C=1NC2=CC(=CC=C2C=1Cl)C(=O)NC(C)C)C(C)(C)C AHVGUCBWHJIREZ-UHFFFAOYSA-N 0.000 claims description 3
- ZKCVPKGPHDGZDJ-UHFFFAOYSA-N 2-(4-amino-1-tert-butylpyrazolo[3,4-d]pyrimidin-3-yl)-N,1-dimethylindole-6-carboxamide Chemical compound CNC(=O)c1ccc2cc(-c3nn(c4ncnc(N)c34)C(C)(C)C)n(C)c2c1 ZKCVPKGPHDGZDJ-UHFFFAOYSA-N 0.000 claims description 3
- VYARLCVNNHTNAM-UHFFFAOYSA-N 2-(4-amino-7-propan-2-ylimidazo[5,1-f][1,2,4]triazin-5-yl)-3-chloro-N-methyl-1H-indole-6-carboxamide Chemical compound NC1=NC=NN2C1=C(N=C2C(C)C)C=1NC2=CC(=CC=C2C=1Cl)C(=O)NC VYARLCVNNHTNAM-UHFFFAOYSA-N 0.000 claims description 3
- DILHJTZQDCOPRO-UHFFFAOYSA-N 2-(4-amino-7-propan-2-ylpyrrolo[2,1-f][1,2,4]triazin-5-yl)-3-chloro-N-methyl-1H-indole-6-carboxamide Chemical compound NC1=NC=NN2C1=C(C=C2C(C)C)C=1NC2=CC(=CC=C2C=1Cl)C(=O)NC DILHJTZQDCOPRO-UHFFFAOYSA-N 0.000 claims description 3
- IHZHNFHAODVCHG-UHFFFAOYSA-N 2-(4-aminothieno[2,3-d]pyrimidin-5-yl)-N-methyl-1H-indole-6-carboxamide Chemical compound CNC(=O)c1ccc2cc([nH]c2c1)-c1csc2ncnc(N)c12 IHZHNFHAODVCHG-UHFFFAOYSA-N 0.000 claims description 3
- VDNPELONOYHGLO-UHFFFAOYSA-N 2-(8-amino-3-propan-2-ylimidazo[1,5-a]pyrazin-1-yl)-N-methyl-1H-indole-6-carboxamide Chemical compound CNC(=O)c1ccc2cc([nH]c2c1)-c1nc(C(C)C)n2ccnc(N)c12 VDNPELONOYHGLO-UHFFFAOYSA-N 0.000 claims description 3
- CZHZUJVGXKKWOK-UHFFFAOYSA-N 2-[4-amino-1-(1-methylpiperidin-4-yl)pyrazolo[3,4-d]pyrimidin-3-yl]-3-chloro-N-cyclopropyl-1H-indole-6-carboxamide Chemical compound NC1=C2C(=NC=N1)N(N=C2C=1NC2=CC(=CC=C2C=1Cl)C(=O)NC1CC1)C1CCN(CC1)C CZHZUJVGXKKWOK-UHFFFAOYSA-N 0.000 claims description 3
- HDRICYBPUIHGFB-UHFFFAOYSA-N 2-[4-amino-1-(1-methylsulfonylpiperidin-4-yl)pyrazolo[3,4-d]pyrimidin-3-yl]-3-chloro-N-methyl-1H-indole-6-carboxamide Chemical compound NC1=C2C(=NC=N1)N(N=C2C=1NC2=CC(=CC=C2C=1Cl)C(=O)NC)C1CCN(CC1)S(=O)(=O)C HDRICYBPUIHGFB-UHFFFAOYSA-N 0.000 claims description 3
- ZMQADKSJKPBTEQ-UHFFFAOYSA-N 2-[4-amino-1-(2-aminoethyl)pyrazolo[3,4-d]pyrimidin-3-yl]-3-chloro-N-methyl-1H-indole-6-carboxamide Chemical compound NC1=C2C(=NC=N1)N(N=C2C=1NC2=CC(=CC=C2C=1Cl)C(=O)NC)CCN ZMQADKSJKPBTEQ-UHFFFAOYSA-N 0.000 claims description 3
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Classifications
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- 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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- A—HUMAN NECESSITIES
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- 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
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/4353—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems
- A61K31/437—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
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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
- A61K31/4985—Pyrazines or piperazines ortho- or peri-condensed with heterocyclic ring systems
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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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- A—HUMAN NECESSITIES
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- 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
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- 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
- C07D471/02—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 two hetero rings
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
- C07D495/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D495/04—Ortho-condensed systems
-
- 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
Landscapes
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Pyridine Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
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| GB201619277 | 2016-11-14 | ||
| PCT/GB2017/051076 WO2017178844A1 (en) | 2016-04-15 | 2017-04-18 | Heterocyclic compounds as ret kinase inhibitors |
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| HUE044025T2 (hu) | 2010-05-20 | 2019-09-30 | Array Biopharma Inc | Makrociklusos vegyületek mint TRK-kináz inhibitorok |
| PL3322706T3 (pl) | 2015-07-16 | 2021-07-19 | Array Biopharma, Inc. | Podstawione związki pirazolo[1,5-a]pirydynowe jako inhibitory kinazy ret |
| RS65069B1 (sr) | 2015-11-02 | 2024-02-29 | Blueprint Medicines Corp | Inhibitori ret-a |
| CN115650985B (zh) | 2016-04-15 | 2024-08-02 | 癌症研究科技有限公司 | 作为ret激酶抑制剂的杂环化合物 |
| WO2017178845A1 (en) | 2016-04-15 | 2017-10-19 | Cancer Research Technology Limited | Heterocyclic compounds as ret kinase inhibitors |
| TWI704148B (zh) | 2016-10-10 | 2020-09-11 | 美商亞雷生物製藥股份有限公司 | 作為ｒｅｔ激酶抑制劑之經取代吡唑并[1,5-a]吡啶化合物 |
| JOP20190077A1 (ar) | 2016-10-10 | 2019-04-09 | Array Biopharma Inc | مركبات بيرازولو [1، 5-a]بيريدين بها استبدال كمثبطات كيناز ret |
| WO2018136663A1 (en) | 2017-01-18 | 2018-07-26 | Array Biopharma, Inc. | Ret inhibitors |
| US11168090B2 (en) | 2017-01-18 | 2021-11-09 | Array Biopharma Inc. | Substituted pyrazolo[1,5-a]pyrazines as RET kinase inhibitors |
| JOP20190213A1 (ar) | 2017-03-16 | 2019-09-16 | Array Biopharma Inc | مركبات حلقية ضخمة كمثبطات لكيناز ros1 |
| GB201705971D0 (en) | 2017-04-13 | 2017-05-31 | Cancer Res Tech Ltd | Inhibitor compounds |
| TWI876442B (zh) | 2017-10-10 | 2025-03-11 | 美商絡速藥業公司 | 6-(2-羥基-2-甲基丙氧基)-4-(6-(6-((6-甲氧基吡啶-3-基)甲基)-3,6-二氮雜雙環[3.1.1]庚-3-基)吡啶-3-基)吡唑并[1,5-a]吡啶-3-甲腈之調配物 |
| TWI791053B (zh) | 2017-10-10 | 2023-02-01 | 美商亞雷生物製藥股份有限公司 | 6-(2-羥基-2-甲基丙氧基)-4-(6-(6-((6-甲氧基吡啶-3-基)甲基)-3,6-二氮雜雙環[3.1.1]庚-3-基)吡啶-3-基)吡唑并[1,5-a]吡啶-3-甲腈之結晶形式及其醫藥組合物 |
| KR20190043437A (ko) | 2017-10-18 | 2019-04-26 | 씨제이헬스케어 주식회사 | 단백질 키나제 억제제로서의 헤테로고리 화합물 |
| EP3740491A1 (en) | 2018-01-18 | 2020-11-25 | Array Biopharma, Inc. | Substituted pyrrolo[2,3-d]pyrimidines compounds as ret kinase inhibitors |
| EP3740486A1 (en) | 2018-01-18 | 2020-11-25 | Array Biopharma, Inc. | Substituted pyrazolyl[4,3-c]pyridinecompounds as ret kinase inhibitors |
| CA3087578C (en) | 2018-01-18 | 2023-08-08 | Array Biopharma Inc. | Substituted pyrazolo[3,4-d]pyrimidine compounds as ret kinase inhibitors |
| FI3773589T3 (fi) | 2018-04-03 | 2024-02-01 | Blueprint Medicines Corp | Ret-estäjä käytettäväksi ret-muunnoksen sisältävän syövän hoidossa |
| US11873303B2 (en) * | 2018-04-05 | 2024-01-16 | Merck Patent Gmbh | Substituted pyrazoles as type II IRAK inhibitors |
| WO2020055672A1 (en) | 2018-09-10 | 2020-03-19 | Array Biopharma Inc. | Fused heterocyclic compounds as ret kinase inhibitors |
| LT3860998T (lt) | 2018-10-05 | 2024-06-25 | Annapurna Bio Inc. | Junginiai ir kompozicijos, skirti gydyti būkles, susijusias su apj receptoriaus aktyvumu |
| KR102195348B1 (ko) | 2018-11-15 | 2020-12-24 | 에이치케이이노엔 주식회사 | 단백질 키나제 억제제로서의 신규 화합물 및 이를 포함하는 약제학적 조성물 |
| JP7291243B2 (ja) * | 2019-04-03 | 2023-06-14 | 広州白雲山医薬集団股分有限公司白雲山制薬総廠 | Ｒｅｔ阻害剤としてのピラゾロピリジン系化合物及びその使用 |
| WO2021023209A1 (zh) * | 2019-08-05 | 2021-02-11 | 北京志健金瑞生物医药科技有限公司 | 含氮多环稠环类化合物，其药物组合物、制备方法和用途 |
| WO2021164742A1 (zh) * | 2020-02-20 | 2021-08-26 | 广州白云山医药集团股份有限公司白云山制药总厂 | 喹啉类化合物 |
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