JP2020503271A5 - - Google Patents
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- JP2020503271A5 JP2020503271A5 JP2019528807A JP2019528807A JP2020503271A5 JP 2020503271 A5 JP2020503271 A5 JP 2020503271A5 JP 2019528807 A JP2019528807 A JP 2019528807A JP 2019528807 A JP2019528807 A JP 2019528807A JP 2020503271 A5 JP2020503271 A5 JP 2020503271A5
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- JP
- Japan
- Prior art keywords
- amino
- compound according
- chloro
- phenyl
- methoxy
- 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.)
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- 150000001875 compounds Chemical class 0.000 claims description 129
- 125000000217 alkyl group Chemical group 0.000 claims description 81
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 41
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 40
- 229910052736 halogen Inorganic materials 0.000 claims description 40
- 150000002367 halogens Chemical class 0.000 claims description 40
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 38
- 229910052799 carbon Inorganic materials 0.000 claims description 34
- -1 and Chemical group 0.000 claims description 33
- 125000003545 alkoxy group Chemical group 0.000 claims description 32
- 229910052739 hydrogen Inorganic materials 0.000 claims description 31
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 31
- 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 claims description 26
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 26
- 125000004432 carbon atom Chemical group C* 0.000 claims description 25
- 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims description 22
- WQAWEUZTDVWTDB-UHFFFAOYSA-N dimethyl(oxo)phosphanium Chemical compound C[P+](C)=O WQAWEUZTDVWTDB-UHFFFAOYSA-N 0.000 claims description 19
- 229910052805 deuterium Inorganic materials 0.000 claims description 18
- 150000003839 salts Chemical class 0.000 claims description 18
- 125000001424 substituent group Chemical group 0.000 claims description 18
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 15
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 13
- 125000003118 aryl group Chemical group 0.000 claims description 12
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 10
- 125000006577 C1-C6 hydroxyalkyl group Chemical group 0.000 claims description 8
- 101001059991 Homo sapiens Mitogen-activated protein kinase kinase kinase kinase 1 Proteins 0.000 claims description 8
- 102100028199 Mitogen-activated protein kinase kinase kinase kinase 1 Human genes 0.000 claims description 8
- 125000001072 heteroaryl group Chemical group 0.000 claims description 8
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 8
- 239000000651 prodrug Substances 0.000 claims description 8
- 229940002612 prodrug Drugs 0.000 claims description 8
- 239000012453 solvate Substances 0.000 claims description 8
- 201000010099 disease Diseases 0.000 claims description 7
- 125000004737 (C1-C6) haloalkoxy group Chemical group 0.000 claims description 6
- 208000035475 disorder Diseases 0.000 claims description 6
- 125000001153 fluoro group Chemical group F* 0.000 claims description 6
- 125000001188 haloalkyl group Chemical group 0.000 claims description 6
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 6
- 230000001404 mediated effect Effects 0.000 claims description 6
- 125000004043 oxo group Chemical group O=* 0.000 claims description 6
- 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 claims description 4
- 125000004429 atom Chemical group 0.000 claims description 4
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 4
- 125000004663 dialkyl amino group Chemical group 0.000 claims description 4
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 4
- 229910052757 nitrogen Inorganic materials 0.000 claims description 4
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 4
- 229910052760 oxygen Inorganic materials 0.000 claims description 4
- 206010061218 Inflammation Diseases 0.000 claims description 3
- 206010027476 Metastases Diseases 0.000 claims description 3
- 206010028980 Neoplasm Diseases 0.000 claims description 3
- 230000001363 autoimmune Effects 0.000 claims description 3
- 201000011510 cancer Diseases 0.000 claims description 3
- 230000004054 inflammatory process Effects 0.000 claims description 3
- 230000009401 metastasis Effects 0.000 claims description 3
- 125000006705 (C5-C7) cycloalkyl group Chemical group 0.000 claims description 2
- KDXVHFUSESBPAJ-UHFFFAOYSA-N 2-N-(5-bromo-2-methyl-3,4-dihydro-1H-isoquinolin-7-yl)-5-chloro-4-N-(2-dimethylphosphorylphenyl)pyrimidine-2,4-diamine Chemical compound CN1CCC2=C(C1)C=C(NC1=NC(NC3=C(C=CC=C3)P(C)(C)=O)=C(Cl)C=N1)C=C2Br KDXVHFUSESBPAJ-UHFFFAOYSA-N 0.000 claims description 2
- WSWVNNMGZOPQPJ-UHFFFAOYSA-N 2-[[5-chloro-2-[(6-methoxy-2-methyl-3,4-dihydro-1H-isoquinolin-7-yl)amino]pyrimidin-4-yl]amino]-N,N-dimethylbenzenesulfonamide Chemical compound COC1=CC2=C(CN(C)CC2)C=C1NC1=NC(NC2=C(C=CC=C2)S(=O)(=O)N(C)C)=C(Cl)C=N1 WSWVNNMGZOPQPJ-UHFFFAOYSA-N 0.000 claims description 2
- DSIDJCGDDHITGX-UHFFFAOYSA-N 2-[[5-chloro-2-[(6-methoxy-2-methyl-3,4-dihydro-1H-isoquinolin-7-yl)amino]pyrimidin-4-yl]amino]-N-methylbenzamide Chemical compound CNC(=O)C1=C(NC2=C(Cl)C=NC(NC3=CC4=C(CCN(C)C4)C=C3OC)=N2)C=CC=C1 DSIDJCGDDHITGX-UHFFFAOYSA-N 0.000 claims description 2
- ZXCLJAYBOJECIX-UHFFFAOYSA-N 4-N-(2-dimethylphosphorylphenyl)-2-N-(6-methoxy-2-methyl-3,4-dihydro-1H-isoquinolin-7-yl)-5-(trifluoromethyl)pyrimidine-2,4-diamine Chemical compound COC1=CC2=C(CN(C)CC2)C=C1NC1=NC(NC2=C(C=CC=C2)P(C)(C)=O)=C(C=N1)C(F)(F)F ZXCLJAYBOJECIX-UHFFFAOYSA-N 0.000 claims description 2
- FQPWWXCVRKPESV-UHFFFAOYSA-N 4-N-(2-dimethylphosphorylphenyl)-5-ethenyl-2-N-(6-methoxy-2-methyl-3,4-dihydro-1H-isoquinolin-7-yl)pyrimidine-2,4-diamine Chemical compound COC=1C=C2CCN(CC2=CC=1NC1=NC=C(C(=N1)NC1=C(C=CC=C1)P(C)(C)=O)C=C)C FQPWWXCVRKPESV-UHFFFAOYSA-N 0.000 claims description 2
- KMGVAIZSYSAYER-UHFFFAOYSA-N 4-N-(2-dimethylphosphorylphenyl)-5-fluoro-2-N-(6-methoxy-2-methyl-3,4-dihydro-1H-isoquinolin-7-yl)pyrimidine-2,4-diamine Chemical compound COC1=CC2=C(CN(C)CC2)C=C1NC1=NC(NC2=C(C=CC=C2)P(C)(C)=O)=C(F)C=N1 KMGVAIZSYSAYER-UHFFFAOYSA-N 0.000 claims description 2
- VWQWFOYWQBTTRH-UHFFFAOYSA-N 4-N-(2-dimethylphosphorylphenyl)-5-methoxy-2-N-(6-methoxy-2-methyl-3,4-dihydro-1H-isoquinolin-7-yl)pyrimidine-2,4-diamine Chemical compound COc1cc2CCN(C)Cc2cc1Nc1ncc(OC)c(Nc2ccccc2P(C)(C)=O)n1 VWQWFOYWQBTTRH-UHFFFAOYSA-N 0.000 claims description 2
- KCALPMNDTLQRTH-UHFFFAOYSA-N 5-bromo-4-N-(2-dimethylphosphorylphenyl)-2-N-(6-methoxy-2-methyl-3,4-dihydro-1H-isoquinolin-7-yl)pyrimidine-2,4-diamine Chemical compound COC1=CC2=C(CN(C)CC2)C=C1NC1=NC(NC2=C(C=CC=C2)P(C)(C)=O)=C(Br)C=N1 KCALPMNDTLQRTH-UHFFFAOYSA-N 0.000 claims description 2
- CVICEEPAFUYBJG-UHFFFAOYSA-N 5-chloro-2,2-difluoro-1,3-benzodioxole Chemical group C1=C(Cl)C=C2OC(F)(F)OC2=C1 CVICEEPAFUYBJG-UHFFFAOYSA-N 0.000 claims description 2
- JWZUKVXRKDHRBL-XUWBISKJSA-N 5-chloro-2-N-(1,1-dideuterio-6-methoxy-3,4-dihydro-2H-isoquinolin-7-yl)-4-N-(2-dimethylphosphorylphenyl)pyrimidine-2,4-diamine Chemical compound ClC=1C(=NC(=NC=1)NC1=C(C=C2CCNC(C2=C1)([2H])[2H])OC)NC1=C(C=CC=C1)P(C)(C)=O JWZUKVXRKDHRBL-XUWBISKJSA-N 0.000 claims description 2
- QKUPFBJAQPFYLF-UHFFFAOYSA-N 5-chloro-2-N-(6-chloro-2-methyl-3,4-dihydro-1H-isoquinolin-7-yl)-4-N-(2-diethylphosphorylphenyl)pyrimidine-2,4-diamine Chemical compound ClC=1C(=NC(=NC=1)NC1=C(C=C2CCN(CC2=C1)C)Cl)NC1=C(C=CC=C1)P(CC)(CC)=O QKUPFBJAQPFYLF-UHFFFAOYSA-N 0.000 claims description 2
- YDGQSMDKANRAGC-UHFFFAOYSA-N 5-chloro-2-N-(6-chloro-2-methyl-3,4-dihydro-1H-isoquinolin-7-yl)-4-N-(2-dimethylphosphorylphenyl)pyrimidine-2,4-diamine Chemical compound CN1CCC2=CC(Cl)=C(NC3=NC=C(Cl)C(NC4=CC=CC=C4P(C)(C)=O)=N3)C=C2C1 YDGQSMDKANRAGC-UHFFFAOYSA-N 0.000 claims description 2
- NALCFIMWIMQFHB-UHFFFAOYSA-N 5-chloro-2-N-(7-chloro-2-methyl-3,4-dihydro-1H-isoquinolin-6-yl)-4-N-(2-dimethylphosphorylphenyl)pyrimidine-2,4-diamine Chemical compound CN1CCc2cc(Nc3ncc(Cl)c(Nc4ccccc4P(C)(C)=O)n3)c(Cl)cc2C1 NALCFIMWIMQFHB-UHFFFAOYSA-N 0.000 claims description 2
- QZQVFEBSSZKRST-UHFFFAOYSA-N 5-chloro-2-N-[2-(dimethylamino)-6-methoxy-2,3-dihydro-1H-inden-5-yl]-4-N-(2-dimethylphosphorylphenyl)pyrimidine-2,4-diamine Chemical compound ClC=1C(=NC(=NC=1)NC=1C=C2CC(CC2=CC=1OC)N(C)C)NC1=C(C=CC=C1)P(C)(C)=O QZQVFEBSSZKRST-UHFFFAOYSA-N 0.000 claims description 2
- PCQCOJFILICLRG-UHFFFAOYSA-N 5-chloro-4-N-(2-diethylphosphorylphenyl)-2-N-(6-methoxy-2-methyl-3,4-dihydro-1H-isoquinolin-7-yl)pyrimidine-2,4-diamine Chemical compound ClC=1C(=NC(=NC=1)NC1=C(C=C2CCN(CC2=C1)C)OC)NC1=C(C=CC=C1)P(CC)(CC)=O PCQCOJFILICLRG-UHFFFAOYSA-N 0.000 claims description 2
- HVDMUQVAANCBIM-UHFFFAOYSA-N 5-chloro-4-N-(2-dimethylphosphorylphenyl)-2-N-(6-ethenyl-2-methyl-3,4-dihydro-1H-isoquinolin-7-yl)pyrimidine-2,4-diamine Chemical compound ClC=1C(=NC(=NC=1)NC1=C(C=C2CCN(CC2=C1)C)C=C)NC1=C(C=CC=C1)P(=O)(C)C HVDMUQVAANCBIM-UHFFFAOYSA-N 0.000 claims description 2
- OEJBKISZXAVCHL-UHFFFAOYSA-N 5-chloro-4-N-(2-dimethylphosphorylphenyl)-2-N-(6-ethoxy-2-methyl-3,4-dihydro-1H-isoquinolin-7-yl)pyrimidine-2,4-diamine Chemical compound ClC=1C(=NC(=NC=1)NC1=C(C=C2CCN(CC2=C1)C)OCC)NC1=C(C=CC=C1)P(C)(C)=O OEJBKISZXAVCHL-UHFFFAOYSA-N 0.000 claims description 2
- SWYNJFAPAFZRMF-UHFFFAOYSA-N 5-chloro-4-N-(2-dimethylphosphorylphenyl)-2-N-(6-ethyl-2-methyl-3,4-dihydro-1H-isoquinolin-7-yl)pyrimidine-2,4-diamine Chemical compound ClC=1C(=NC(=NC=1)NC1=C(C=C2CCN(CC2=C1)C)CC)NC1=C(C=CC=C1)P(=O)(C)C SWYNJFAPAFZRMF-UHFFFAOYSA-N 0.000 claims description 2
- ZSAIMPBXGWCIEV-UHFFFAOYSA-N 5-chloro-4-N-(2-dimethylphosphorylphenyl)-2-N-(6-fluoro-2-methyl-3,4-dihydro-1H-isoquinolin-7-yl)pyrimidine-2,4-diamine Chemical compound CN1CCC2=C(C1)C=C(NC1=NC(NC3=C(C=CC=C3)P(C)(C)=O)=C(Cl)C=N1)C(F)=C2 ZSAIMPBXGWCIEV-UHFFFAOYSA-N 0.000 claims description 2
- FLCNVWSKXSRARI-UHFFFAOYSA-N 5-chloro-4-N-(2-dimethylphosphorylphenyl)-2-N-(6-methoxy-1,1,2-trimethyl-3,4-dihydroisoquinolin-7-yl)pyrimidine-2,4-diamine Chemical compound ClC=1C(=NC(=NC=1)NC1=C(C=C2CCN(C(C2=C1)(C)C)C)OC)NC1=C(C=CC=C1)P(C)(C)=O FLCNVWSKXSRARI-UHFFFAOYSA-N 0.000 claims description 2
- JWZUKVXRKDHRBL-UHFFFAOYSA-N 5-chloro-4-N-(2-dimethylphosphorylphenyl)-2-N-(6-methoxy-1,2,3,4-tetrahydroisoquinolin-7-yl)pyrimidine-2,4-diamine Chemical compound COC1=CC2=C(CNCC2)C=C1NC1=NC(NC2=C(C=CC=C2)P(C)(C)=O)=C(Cl)C=N1 JWZUKVXRKDHRBL-UHFFFAOYSA-N 0.000 claims description 2
- ZIIMDSSVIOLWDT-UHFFFAOYSA-N 5-chloro-4-N-(2-dimethylphosphorylphenyl)-2-N-(6-methoxy-1,2-dimethyl-3,4-dihydro-1H-isoquinolin-7-yl)pyrimidine-2,4-diamine Chemical compound COC1=CC2=C(C=C1NC1=NC(NC3=C(C=CC=C3)P(C)(C)=O)=C(Cl)C=N1)C(C)N(C)CC2 ZIIMDSSVIOLWDT-UHFFFAOYSA-N 0.000 claims description 2
- CFYLJYBFMCKWRT-UHFFFAOYSA-N 5-chloro-4-N-(2-dimethylphosphorylphenyl)-2-N-(6-methoxy-2,4,4-trimethyl-1,3-dihydroisoquinolin-7-yl)pyrimidine-2,4-diamine Chemical compound COC1=CC2=C(CN(C)CC2(C)C)C=C1NC1=NC(NC2=C(C=CC=C2)P(C)(C)=O)=C(Cl)C=N1 CFYLJYBFMCKWRT-UHFFFAOYSA-N 0.000 claims description 2
- PKCVIEAEQWBROQ-UHFFFAOYSA-N 5-chloro-4-N-(2-dimethylphosphorylphenyl)-2-N-(6-methoxy-2-methyl-1,3-dihydroisoindol-5-yl)pyrimidine-2,4-diamine Chemical compound ClC=1C(=NC(=NC=1)NC=1C=C2CN(CC2=CC=1OC)C)NC1=C(C=CC=C1)P(C)(C)=O PKCVIEAEQWBROQ-UHFFFAOYSA-N 0.000 claims description 2
- QWCVGHXDHVKGAQ-UHFFFAOYSA-N 5-chloro-4-N-(2-dimethylphosphorylphenyl)-2-N-(6-methoxy-2-methyl-3,4-dihydro-1H-isoquinolin-7-yl)pyrimidine-2,4-diamine Chemical compound COC1=CC2=C(CN(C)CC2)C=C1NC1=NC(NC2=C(C=CC=C2)P(C)(C)=O)=C(Cl)C=N1 QWCVGHXDHVKGAQ-UHFFFAOYSA-N 0.000 claims description 2
- NFCFFFWUBSUWNP-UHFFFAOYSA-N 5-chloro-4-N-(2-dimethylphosphorylphenyl)-2-N-(6-methoxy-2-propan-2-yl-3,4-dihydro-1H-isoquinolin-7-yl)pyrimidine-2,4-diamine Chemical compound COC1=CC2=C(CN(CC2)C(C)C)C=C1NC1=NC(NC2=C(C=CC=C2)P(C)(C)=O)=C(Cl)C=N1 NFCFFFWUBSUWNP-UHFFFAOYSA-N 0.000 claims description 2
- GLJAYMYZSWMKMI-UHFFFAOYSA-N 5-chloro-4-N-(2-dimethylphosphorylphenyl)-2-N-(6-methoxy-4,4-dimethyl-2,3-dihydro-1H-isoquinolin-7-yl)pyrimidine-2,4-diamine Chemical compound COC1=CC2=C(CNCC2(C)C)C=C1NC1=NC(NC2=C(C=CC=C2)P(C)(C)=O)=C(Cl)C=N1 GLJAYMYZSWMKMI-UHFFFAOYSA-N 0.000 claims description 2
- PUWIWAQYKIBXFP-UHFFFAOYSA-N 5-chloro-4-N-(2-dimethylphosphorylphenyl)-2-N-(7-methoxy-1,2,3,4-tetrahydroisoquinolin-6-yl)pyrimidine-2,4-diamine Chemical compound COC1=CC2=C(CCNC2)C=C1NC1=NC(NC2=C(C=CC=C2)P(C)(C)=O)=C(Cl)C=N1 PUWIWAQYKIBXFP-UHFFFAOYSA-N 0.000 claims description 2
- BUGDBYWBQSINKL-UHFFFAOYSA-N 5-chloro-4-N-(2-dimethylphosphorylphenyl)-2-N-(7-methoxy-2-methyl-3,4-dihydro-1H-isoquinolin-6-yl)pyrimidine-2,4-diamine Chemical compound ClC=1C(=NC(=NC=1)NC=1C=C2CCN(CC2=CC=1OC)C)NC1=C(C=CC=C1)P(C)(C)=O BUGDBYWBQSINKL-UHFFFAOYSA-N 0.000 claims description 2
- LXNIIMDKSBVIPM-UHFFFAOYSA-N 5-chloro-4-N-(2-dimethylphosphorylphenyl)-2-N-(9-methoxy-2,3,4,6,11,11a-hexahydro-1H-benzo[b]quinolizin-8-yl)pyrimidine-2,4-diamine Chemical compound ClC=1C(=NC(=NC=1)NC1=CC2=C(CC3CCCCN3C2)C=C1OC)NC1=C(C=CC=C1)P(=O)(C)C LXNIIMDKSBVIPM-UHFFFAOYSA-N 0.000 claims description 2
- DFAKEQRUAJGWMX-UHFFFAOYSA-N 5-chloro-4-N-(2-dimethylphosphorylphenyl)-2-N-[6-(trifluoromethyl)-1,2,3,4-tetrahydroisoquinolin-7-yl]pyrimidine-2,4-diamine Chemical compound CP(C)(=O)C1=C(NC2=C(Cl)C=NC(NC3=CC4=C(CCNC4)C=C3C(F)(F)F)=N2)C=CC=C1 DFAKEQRUAJGWMX-UHFFFAOYSA-N 0.000 claims description 2
- XEUXLBPKFACCHV-UHFFFAOYSA-N 5-chloro-4-N-(2-dimethylphosphorylphenyl)-2-N-[6-methoxy-2-(oxetan-3-yl)-3,4-dihydro-1H-isoquinolin-7-yl]pyrimidine-2,4-diamine Chemical compound COC1=CC2=C(CN(CC2)C2COC2)C=C1NC1=NC(NC2=C(C=CC=C2)P(C)(C)=O)=C(Cl)C=N1 XEUXLBPKFACCHV-UHFFFAOYSA-N 0.000 claims description 2
- 125000003282 alkyl amino group Chemical group 0.000 claims description 2
- 239000003085 diluting agent Substances 0.000 claims description 2
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 2
- 239000008194 pharmaceutical composition Substances 0.000 claims description 2
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 2
- 125000004437 phosphorous atom Chemical group 0.000 claims description 2
- 229910052698 phosphorus Inorganic materials 0.000 claims description 2
- YAAWASYJIRZXSZ-UHFFFAOYSA-N pyrimidine-2,4-diamine Chemical compound NC1=CC=NC(N)=N1 YAAWASYJIRZXSZ-UHFFFAOYSA-N 0.000 claims description 2
- 238000006467 substitution reaction Methods 0.000 claims description 2
- 229910052717 sulfur Inorganic materials 0.000 claims description 2
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 2
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 claims description 2
- 239000000203 mixture Substances 0.000 claims 7
- CORHJJNVWGMXIV-UHFFFAOYSA-N 8-[[5-chloro-4-(2-dimethylphosphorylanilino)pyrimidin-2-yl]amino]-7-methoxy-2-methyl-4,5-dihydro-3H-2-benzazepin-1-one Chemical compound ClC=1C(=NC(=NC=1)NC=1C(=CC2=C(C(N(CCC2)C)=O)C=1)OC)NC1=C(C=CC=C1)P(=O)(C)C CORHJJNVWGMXIV-UHFFFAOYSA-N 0.000 claims 1
- HGDIHUZVQPKSMO-UHFFFAOYSA-N methylphosphonoylmethane Chemical compound CP(C)=O HGDIHUZVQPKSMO-UHFFFAOYSA-N 0.000 claims 1
- 125000004527 pyrimidin-4-yl group Chemical group N1=CN=C(C=C1)* 0.000 claims 1
- 238000000034 method Methods 0.000 description 8
- 0 *C1(*)c2cc(Nc3ncc(*)c(Nc4c(*)cccc4)n3)c(*)cc2*CC*1 Chemical compound *C1(*)c2cc(Nc3ncc(*)c(Nc4c(*)cccc4)n3)c(*)cc2*CC*1 0.000 description 3
- BRXHMPPDBUOUQS-UHFFFAOYSA-N 4-N-(2-dimethylphosphorylphenyl)-2-N-(6-methoxy-2-methyl-3,4-dihydro-1H-isoquinolin-7-yl)pyrimidine-2,4-diamine Chemical compound COC1=CC2=C(CN(C)CC2)C=C1NC1=NC(NC2=C(C=CC=C2)P(C)(C)=O)=CC=N1 BRXHMPPDBUOUQS-UHFFFAOYSA-N 0.000 description 1
- YXJNHAGAOHGMPU-UHFFFAOYSA-N CCC1=CN=C(NC(C=C(CN(C)CC2)C2=C2)=C2OC)N=C1NC(C=CC=C1)=C1P(C)C Chemical compound CCC1=CN=C(NC(C=C(CN(C)CC2)C2=C2)=C2OC)N=C1NC(C=CC=C1)=C1P(C)C YXJNHAGAOHGMPU-UHFFFAOYSA-N 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 208000037765 diseases and disorders Diseases 0.000 description 1
- 230000010534 mechanism of action Effects 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 description 1
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201662428191P | 2016-11-30 | 2016-11-30 | |
| US62/428,191 | 2016-11-30 | ||
| PCT/US2017/063633 WO2018102366A1 (en) | 2016-11-30 | 2017-11-29 | Anilinopyrimidines as haematopoietic progenitor kinase 1 (hpk1) inhibitors |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2020503271A JP2020503271A (ja) | 2020-01-30 |
| JP2020503271A5 true JP2020503271A5 (enExample) | 2021-01-07 |
| JP7025426B2 JP7025426B2 (ja) | 2022-02-24 |
Family
ID=60629854
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2019528807A Active JP7025426B2 (ja) | 2016-11-30 | 2017-11-29 | 造血前駆体キナーゼ１（ｈｐｋ１）阻害剤としてのアニリノピリミジンａｓ |
Country Status (5)
| Country | Link |
|---|---|
| US (1) | US11180482B2 (enExample) |
| EP (1) | EP3548479A1 (enExample) |
| JP (1) | JP7025426B2 (enExample) |
| MA (1) | MA46942A (enExample) |
| WO (1) | WO2018102366A1 (enExample) |
Families Citing this family (86)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| SG11201908940UA (en) | 2017-03-30 | 2019-10-30 | Hoffmann La Roche | Isoquinolines as inhibitors of hpk1 |
| WO2019090198A1 (en) | 2017-11-06 | 2019-05-09 | Bristol-Myers Squibb Company | Isofuranone compounds useful as hpk1 inhibitors |
| TW202012405A (zh) * | 2018-07-24 | 2020-04-01 | 瑞士商赫孚孟拉羅股份公司 | 萘啶化合物及其用途 |
| TW202019905A (zh) | 2018-07-24 | 2020-06-01 | 瑞士商赫孚孟拉羅股份公司 | 異喹啉化合物及其用途 |
| CN113454070A (zh) * | 2018-09-30 | 2021-09-28 | 豪夫迈·罗氏有限公司 | 噌啉化合物及用于hpk1依赖性疾患诸如癌症的治疗 |
| TW202024053A (zh) | 2018-10-02 | 2020-07-01 | 美商建南德克公司 | 異喹啉化合物及其用途 |
| US11612606B2 (en) | 2018-10-03 | 2023-03-28 | Genentech, Inc. | 8-aminoisoquinoline compounds and uses thereof |
| PE20211655A1 (es) | 2018-10-31 | 2021-08-24 | Gilead Sciences Inc | Compuestos de 6-azabencimidazol sustituidos como inhibidores de hpk1 |
| WO2020092528A1 (en) * | 2018-10-31 | 2020-05-07 | Gilead Sciences, Inc. | Substituted 6-azabenzimidazole compounds having hpk1 inhibitory activity |
| US20220047603A1 (en) | 2018-12-11 | 2022-02-17 | Bayer Aktiengesellschaft | Substituted pyrrolopyridine-derivatives |
| US12492194B2 (en) | 2019-03-26 | 2025-12-09 | Janssen Pharmaceutica Nv | HPK1 inhibitors |
| CA3129772A1 (en) | 2019-03-26 | 2020-10-01 | Janssen Pharmaceutica Nv | Bicyclic hpk1 inhibitors |
| TWI826690B (zh) | 2019-05-23 | 2023-12-21 | 美商基利科學股份有限公司 | 經取代之烯吲哚酮化物及其用途 |
| AU2020301161B2 (en) | 2019-06-25 | 2023-10-26 | Gilead Sciences, Inc. | FLT3L-Fc fusion proteins and methods of use |
| US12612424B2 (en) | 2019-07-04 | 2026-04-28 | Regor Pharmaceuticals, Inc. | HPK1 inhibitors and uses thereof |
| TW202116753A (zh) * | 2019-07-11 | 2021-05-01 | 大陸商南京征祥醫藥有限公司 | 以噌啉作為hpk1的抑制劑 |
| CN110428982B (zh) * | 2019-07-31 | 2021-03-02 | 太仓碧奇新材料研发有限公司 | 一种超级电容器隔膜的制备方法 |
| PH12022550605A1 (en) | 2019-09-13 | 2023-09-25 | Nimbus Saturn Inc | Hpk1 antagonists and uses thereof |
| KR102902719B1 (ko) | 2019-10-18 | 2025-12-24 | 포티 세븐, 엘엘씨 | 골수이형성 증후군 및 급성 골수성 백혈병을 치료하기 위한 조합 치료 |
| CA3153636A1 (en) | 2019-10-31 | 2021-05-06 | Forty Seven, Inc. | Anti-cd47 and anti-cd20 based treatment of blood cancer |
| TWI778443B (zh) | 2019-11-12 | 2022-09-21 | 美商基利科學股份有限公司 | Mcl1抑制劑 |
| CA3161667A1 (en) * | 2019-12-16 | 2021-06-24 | Pil Ho Kim | Novel pyrimidine derivative and use thereof |
| AU2020406824A1 (en) * | 2019-12-16 | 2022-08-11 | Korea Research Institute Of Chemical Technology | Novel pyrimidine derivative and use thereof |
| EP4445902A3 (en) | 2019-12-24 | 2024-12-18 | Carna Biosciences, Inc. | Diacylglycerol kinase modulating compounds |
| TW202140473A (zh) * | 2020-01-15 | 2021-11-01 | 美商纜圖藥品公司 | Map4k1抑制劑 |
| CN117964757A (zh) | 2020-02-14 | 2024-05-03 | 吉利德科学公司 | 与ccr8结合的抗体和融合蛋白及其用途 |
| AU2021218739A1 (en) * | 2020-02-14 | 2022-09-22 | Salk Institute For Biological Studies | Inhibitors of ULK1/2 and methods of using same |
| CN115515588A (zh) | 2020-02-14 | 2022-12-23 | 萨克生物研究学院 | 大环ulk1/2抑制剂 |
| KR20230002721A (ko) * | 2020-04-14 | 2023-01-05 | 치루 파머수티컬 컴퍼니 리미티드 | Egfr 억제제로서의 삼환계 화합물 |
| US12110294B2 (en) | 2020-05-01 | 2024-10-08 | Gilead Sciences, Inc. | CD73 compounds |
| JP2023527242A (ja) * | 2020-05-29 | 2023-06-27 | 南京正大天晴制薬有限公司 | Ａｘｌ阻害剤であるピリミジン系化合物 |
| WO2021249913A1 (en) | 2020-06-09 | 2021-12-16 | Bayer Aktiengesellschaft | 2'-(quinolin-3-yl)-5',6'-dihydrospiro[azetidine-3,4'-pyrrolo[1,2-b]pyrazole]-1-carboxylate derivatives and related compounds as map4k1 (hpk1) inhibitors for the treatment of cancer |
| WO2022063140A1 (en) * | 2020-09-23 | 2022-03-31 | Shenzhen Ionova Life Science Co., Ltd. | Pyrimidine and pyridine derivatives as hpk1 modulator and methods using same |
| CN114437074A (zh) | 2020-11-03 | 2022-05-06 | 北京伯汇生物技术有限公司 | 一种化合物、含该化合物的药物组合物及其用途 |
| WO2022098809A1 (en) * | 2020-11-09 | 2022-05-12 | Merck Sharp & Dohme Corp. | Diaminopyrimidine carboxamide inhibitors of hpk1 |
| WO2022100688A1 (zh) * | 2020-11-13 | 2022-05-19 | 南京红云生物科技有限公司 | Hpk1激酶调节剂、其制备方法与应用 |
| CN116472041B (zh) * | 2020-11-24 | 2024-12-06 | 正大天晴药业集团股份有限公司 | 氘修饰的噻吩并吡啶酮化合物 |
| CN121851009A (zh) * | 2021-01-22 | 2026-04-14 | 苏州信诺维医药科技股份有限公司 | Hpk1抑制剂、其制备方法、药物组合物及其应用 |
| US20240174683A1 (en) | 2021-02-05 | 2024-05-30 | Bayer Aktiengesellschaft | Map4k1 inhibitors |
| CN117295748A (zh) * | 2021-03-08 | 2023-12-26 | 缆图药品公司 | Map4k1抑制剂 |
| EP4305041A1 (en) * | 2021-03-08 | 2024-01-17 | Blueprint Medicines Corporation | Map4k1 inhibitors |
| WO2022199561A1 (zh) * | 2021-03-23 | 2022-09-29 | 杭州阿诺生物医药科技有限公司 | Hpk1激酶抑制剂化合物 |
| WO2022199589A1 (zh) * | 2021-03-23 | 2022-09-29 | 南京明德新药研发有限公司 | 嘧啶衍生物 |
| WO2022213062A1 (en) | 2021-03-29 | 2022-10-06 | Nimbus Saturn, Inc. | Hpk1 antagonists and uses thereof |
| TW202304906A (zh) * | 2021-04-08 | 2023-02-01 | 大陸商杭州阿諾生物醫藥科技有限公司 | 高活性hpk1激酶抑制劑 |
| TW202302145A (zh) | 2021-04-14 | 2023-01-16 | 美商基利科學股份有限公司 | ＣＤ４７／ＳＩＲＰα結合及ＮＥＤＤ８活化酶Ｅ１調節次單元之共抑制以用於治療癌症 |
| TW202313094A (zh) | 2021-05-18 | 2023-04-01 | 美商基利科學股份有限公司 | 使用ＦＬＴ３Ｌ—Ｆｃ融合蛋白之方法 |
| WO2022271659A1 (en) | 2021-06-23 | 2022-12-29 | Gilead Sciences, Inc. | Diacylglyercol kinase modulating compounds |
| WO2022271650A1 (en) | 2021-06-23 | 2022-12-29 | Gilead Sciences, Inc. | Diacylglyercol kinase modulating compounds |
| EP4359415A1 (en) | 2021-06-23 | 2024-05-01 | Gilead Sciences, Inc. | Diacylglyercol kinase modulating compounds |
| US11932634B2 (en) | 2021-06-23 | 2024-03-19 | Gilead Sciences, Inc. | Diacylglycerol kinase modulating compounds |
| KR20240012538A (ko) | 2021-07-06 | 2024-01-29 | 글렌마크 스페셜티 에스. 에이. | Map4k1 억제제로 사용하기 위한 피리미딘 화합물 |
| MX2024000751A (es) | 2021-07-14 | 2024-03-25 | Blueprint Medicines Corp | Compuestos heterociclicos como inhibidores de map4k1. |
| EP4373817B1 (en) | 2021-07-20 | 2025-05-21 | Astrazeneca AB | Substituted pyrazine-2-carboxamides as hpk1 inhibitors for the treatment of cancer |
| CN115838373A (zh) * | 2021-09-18 | 2023-03-24 | 北京伯汇生物技术有限公司 | 氮杂吲唑大环化合物及其用途 |
| CN115838383A (zh) * | 2021-09-22 | 2023-03-24 | 南京正大天晴制药有限公司 | 作为axl抑制剂的苯并环庚烷类化合物 |
| AU2022375782B2 (en) | 2021-10-28 | 2026-02-26 | Gilead Sciences, Inc. | Pyridizin-3(2h)-one derivatives |
| AU2022376954B2 (en) | 2021-10-29 | 2026-04-23 | Gilead Sciences, Inc. | Cd73 compounds |
| CN116178434A (zh) * | 2021-11-26 | 2023-05-30 | 南京正大天晴制药有限公司 | Axl激酶抑制剂的单对甲苯磺酸盐及其晶型 |
| CN116178433A (zh) * | 2021-11-26 | 2023-05-30 | 南京正大天晴制药有限公司 | Axl激酶抑制剂的盐及其制备方法和用途 |
| WO2023107956A1 (en) | 2021-12-08 | 2023-06-15 | Dragonfly Therapeutics, Inc. | Proteins binding nkg2d, cd16 and 5t4 |
| US20230220106A1 (en) | 2021-12-08 | 2023-07-13 | Dragonfly Therapeutics, Inc. | Antibodies targeting 5t4 and uses thereof |
| CA3237577A1 (en) | 2021-12-22 | 2023-06-29 | Gilead Sciences, Inc. | Ikaros zinc finger family degraders and uses thereof |
| AU2022419982B2 (en) | 2021-12-22 | 2026-04-16 | Gilead Sciences, Inc. | Ikaros zinc finger family degraders and uses thereof |
| TW202340168A (zh) | 2022-01-28 | 2023-10-16 | 美商基利科學股份有限公司 | Ｐａｒｐ７抑制劑 |
| EP4493554A1 (en) | 2022-03-17 | 2025-01-22 | Gilead Sciences, Inc. | Ikaros zinc finger family degraders and uses thereof |
| WO2023183817A1 (en) | 2022-03-24 | 2023-09-28 | Gilead Sciences, Inc. | Combination therapy for treating trop-2 expressing cancers |
| TWI876305B (zh) | 2022-04-05 | 2025-03-11 | 美商基利科學股份有限公司 | 用於治療結腸直腸癌之組合療法 |
| CR20240451A (es) | 2022-04-21 | 2024-12-04 | Gilead Sciences Inc | Compuestos de modulación de kras g12d |
| PE20250758A1 (es) | 2022-07-01 | 2025-03-13 | Gilead Sciences Inc | Compuestos de cd73 |
| WO2024064668A1 (en) | 2022-09-21 | 2024-03-28 | Gilead Sciences, Inc. | FOCAL IONIZING RADIATION AND CD47/SIRPα DISRUPTION ANTICANCER COMBINATION THERAPY |
| CN120225509A (zh) | 2022-12-22 | 2025-06-27 | 吉利德科学公司 | Prmt5抑制剂及其用途 |
| CN118184669B (zh) * | 2023-03-17 | 2025-09-23 | 北京伯汇生物技术有限公司 | 作为多靶点激酶抑制剂的大环化合物 |
| AU2024252725A1 (en) | 2023-04-11 | 2025-11-06 | Gilead Sciences, Inc. | Kras modulating compounds |
| PE20260121A1 (es) | 2023-04-21 | 2026-01-16 | Gilead Sciences Inc | Inhibidores de prmt5 y usos de los mismos |
| AU2024306338A1 (en) | 2023-06-30 | 2026-01-08 | Gilead Sciences, Inc. | Kras modulating compounds |
| WO2025024811A1 (en) | 2023-07-26 | 2025-01-30 | Gilead Sciences, Inc. | Parp7 inhibitors |
| KR20260046403A (ko) | 2023-07-26 | 2026-04-07 | 길리애드 사이언시즈, 인코포레이티드 | Parp7 저해제 |
| US20250101042A1 (en) | 2023-09-08 | 2025-03-27 | Gilead Sciences, Inc. | Kras g12d modulating compounds |
| AU2024337913A1 (en) | 2023-09-08 | 2026-03-26 | Gilead Sciences, Inc. | Pyrimidine-containing polycyclic derivatives as kras g12d modulating compounds |
| KR20250041906A (ko) * | 2023-09-19 | 2025-03-26 | (주)엠디바이오팜 | Hpk1 및 mlk3 저해 활성을 갖는 신규한 화합물 및 이를 함유하는 항암용 조성물 |
| US20250154172A1 (en) | 2023-11-03 | 2025-05-15 | Gilead Sciences, Inc. | Prmt5 inhibitors and uses thereof |
| WO2025137640A1 (en) | 2023-12-22 | 2025-06-26 | Gilead Sciences, Inc. | Azaspiro wrn inhibitors |
| WO2025245003A1 (en) | 2024-05-21 | 2025-11-27 | Gilead Sciences, Inc. | Prmt5 inhibitors and uses thereof |
| WO2026039365A1 (en) | 2024-08-12 | 2026-02-19 | Gilead Sciences, Inc. | Kras modulating compounds |
| WO2026089992A1 (en) | 2024-10-21 | 2026-04-30 | Gilead Sciences, Inc. | Prmt5 inhibitors and uses thereof |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5262564A (en) | 1992-10-30 | 1993-11-16 | Octamer, Inc. | Sulfinic acid adducts of organo nitroso compounds useful as retroviral inactivating agents anti-retroviral agents and anti-tumor agents |
| EP2300013B2 (en) * | 2008-05-21 | 2024-11-13 | Takeda Pharmaceutical Company Limited | Phosphorous derivatives as kinase inhibitors |
| US20140024620A1 (en) * | 2010-10-14 | 2014-01-23 | Ariad Pharmaceuticals, Inc. | Methods for Inhibiting Cell Proliferation in EGFR-Driven Cancers |
| WO2015038868A1 (en) * | 2013-09-13 | 2015-03-19 | Cephalon, Inc. | Fused bicyclic 2,4-diaminopyrimidine derivatives |
| JP6878004B2 (ja) | 2013-12-13 | 2021-05-26 | ダナ−ファーバー キャンサー インスティテュート， インコーポレイテッド | リンパ形質細胞性リンパ腫を処置する方法 |
| JP6622726B2 (ja) * | 2014-06-17 | 2019-12-18 | コリア リサーチ インスティチュート オブ ケミカル テクノロジーＫｏｒｅａ Ｒｅｓｅａｒｃｈ Ｉｎｓｔｉｔｕｔｅ Ｏｆ Ｃｈｅｍｉｃａｌ Ｔｅｃｈｎｏｌｏｇｙ | ピリミジン‐２，４‐ジアミン誘導体及びそれを有効成分として含有する抗癌用医薬組成物 |
-
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- 2017-11-29 MA MA046942A patent/MA46942A/fr unknown
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