JP2020503271A5 - - Google Patents
Download PDFInfo
- Publication number
- 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
- Authority
- 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.)
- Granted
Links
- 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 (https=) | 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 (https=) |
| EP (1) | EP3548479A1 (https=) |
| JP (1) | JP7025426B2 (https=) |
| MA (1) | MA46942A (https=) |
| WO (1) | WO2018102366A1 (https=) |
Families Citing this family (85)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP3601259B1 (en) | 2017-03-30 | 2022-02-23 | F. Hoffmann-La Roche AG | Isoquinolines as inhibitors of hpk1 |
| EP3707138B1 (en) | 2017-11-06 | 2022-07-13 | Bristol-Myers Squibb Company | Isofuranone compounds useful as hpk1 inhibitors |
| 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 |
| 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 |
| EP3856724A1 (en) * | 2018-09-30 | 2021-08-04 | F. Hoffmann-La Roche AG | Cinnoline compounds and for the treatment of hpk1-dependent disorders such as cancer |
| 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 |
| US11203591B2 (en) | 2018-10-31 | 2021-12-21 | Gilead Sciences, Inc. | Substituted 6-azabenzimidazole compounds |
| WO2020092528A1 (en) | 2018-10-31 | 2020-05-07 | Gilead Sciences, Inc. | Substituted 6-azabenzimidazole compounds having hpk1 inhibitory activity |
| WO2020120257A1 (en) | 2018-12-11 | 2020-06-18 | Bayer Aktiengesellschaft | Substituted pyrrolopyridine-derivatives |
| US12486264B2 (en) | 2019-03-26 | 2025-12-02 | Janssen Pharmaceutica Nv | Bicyclic HPK1 inhibitors |
| US12492194B2 (en) | 2019-03-26 | 2025-12-09 | Janssen Pharmaceutica Nv | HPK1 inhibitors |
| EP3972695A1 (en) | 2019-05-23 | 2022-03-30 | Gilead Sciences, Inc. | Substituted exo-methylene-oxindoles which are hpk1/map4k1 inhibitors |
| WO2020263830A1 (en) | 2019-06-25 | 2020-12-30 | Gilead Sciences, Inc. | Flt3l-fc fusion proteins and methods of use |
| MA56462A (fr) | 2019-07-04 | 2022-05-11 | Qilu Regor Therapeutics Inc | Inhibiteurs de hpk1 et leurs utilisations |
| 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 |
| MX2022002877A (es) * | 2019-09-13 | 2022-08-08 | Nimbus Saturn Inc | Antagonistas de cinasa progenitora hematopoyetica 1 (hpk1) y sus usos. |
| ES2973832T3 (es) | 2019-10-18 | 2024-06-24 | Forty Seven Inc | Terapias combinadas para el tratamiento de síndromes mielodisplásicos y leucemia mieloide aguda |
| JP2022552748A (ja) | 2019-10-31 | 2022-12-19 | フォーティ セブン， インコーポレイテッド | 抗ｃｄ４７及び抗ｃｄ２０による血液癌の治療 |
| TWI778443B (zh) | 2019-11-12 | 2022-09-21 | 美商基利科學股份有限公司 | Mcl1抑制劑 |
| AU2020406824A1 (en) * | 2019-12-16 | 2022-08-11 | Korea Research Institute Of Chemical Technology | Novel pyrimidine derivative and use thereof |
| JP7659560B2 (ja) * | 2019-12-16 | 2025-04-09 | 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 | 新規なピリミジン誘導体及びその用途 |
| IL294032A (en) | 2019-12-24 | 2022-08-01 | Carna Biosciences Inc | Compounds that regulate diacylglycerol kinase |
| TW202140473A (zh) * | 2020-01-15 | 2021-11-01 | 美商纜圖藥品公司 | Map4k1抑制劑 |
| KR20220153581A (ko) * | 2020-02-14 | 2022-11-18 | 솔크 인스티튜트 포 바이올로지칼 스터디즈 | Ulk1/2 의 억제제 및 이의 사용 방법 |
| TWI890283B (zh) | 2020-02-14 | 2025-07-11 | 美商基利科學股份有限公司 | 結合ccr8之抗體及融合蛋白及其用途 |
| KR20220153582A (ko) | 2020-02-14 | 2022-11-18 | 솔크 인스티튜트 포 바이올로지칼 스터디즈 | 마크로시클릭 ulk1/2 억제제 |
| KR20230002721A (ko) * | 2020-04-14 | 2023-01-05 | 치루 파머수티컬 컴퍼니 리미티드 | Egfr 억제제로서의 삼환계 화합물 |
| IL297327B2 (en) | 2020-05-01 | 2026-01-01 | Gilead Sciences Inc | 4,2-dioxopyrimidine compounds CD73 inhibitors |
| WO2021239133A1 (zh) * | 2020-05-29 | 2021-12-02 | 南京正大天晴制药有限公司 | 作为axl抑制剂的嘧啶类化合物 |
| 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 |
| US20230416225A1 (en) * | 2020-11-09 | 2023-12-28 | Merck Sharp & Dohme Llc | Diaminopyrimidine carboxamide inhibitors of hpk1 |
| CN116438172A (zh) * | 2020-11-13 | 2023-07-14 | 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 |
| US20240002394A1 (en) * | 2020-11-24 | 2024-01-04 | Chia Tai Tianqing Pharmaceutical Group Co., Ltd. | Deuterium-modified thienopyridone compound |
| 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 |
| 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 |
| CN116854687B (zh) * | 2021-03-23 | 2025-07-25 | 杭州阿诺生物医药科技有限公司 | Hpk1激酶抑制剂化合物 |
| 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 |
| WO2022245671A1 (en) | 2021-05-18 | 2022-11-24 | Gilead Sciences, Inc. | Methods of using flt3l-fc fusion proteins |
| MX2023014762A (es) | 2021-06-23 | 2024-01-15 | Gilead Sciences Inc | Compuestos moduladores de diacilglicerol quinasa. |
| AU2022299051B2 (en) | 2021-06-23 | 2025-03-13 | Gilead Sciences, Inc. | Diacylglyercol kinase modulating compounds |
| JP7651018B2 (ja) | 2021-06-23 | 2025-03-25 | ギリアード サイエンシーズ， インコーポレイテッド | ジアシルグリセロールキナーゼ調節化合物 |
| JP7686091B2 (ja) | 2021-06-23 | 2025-05-30 | ギリアード サイエンシーズ， インコーポレイテッド | ジアシルグリセロールキナーゼ調節化合物 |
| CA3223874A1 (en) | 2021-07-06 | 2023-01-12 | Pravin Iyer | Pyrimidine compounds for use as map4k1 inhibitors |
| WO2023288254A1 (en) * | 2021-07-14 | 2023-01-19 | Blueprint Medicines Corporation | Heterocyclic compounds as map4k1 inhibitors |
| TW202321239A (zh) | 2021-07-20 | 2023-06-01 | 瑞典商阿斯特捷利康公司 | 作為ｈｐｋ１抑制劑用於治療癌症之經取代的吡𠯤—２—甲醯胺 |
| 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 |
| JP7787991B2 (ja) | 2021-10-29 | 2025-12-17 | ギリアード サイエンシーズ， インコーポレイテッド | Ｃｄ７３化合物 |
| 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 |
| US20230220106A1 (en) | 2021-12-08 | 2023-07-13 | Dragonfly Therapeutics, Inc. | Antibodies targeting 5t4 and uses thereof |
| WO2023107956A1 (en) | 2021-12-08 | 2023-06-15 | Dragonfly Therapeutics, Inc. | Proteins binding nkg2d, cd16 and 5t4 |
| US12122764B2 (en) | 2021-12-22 | 2024-10-22 | Gilead Sciences, Inc. | IKAROS zinc finger family degraders and uses thereof |
| KR20240123836A (ko) | 2021-12-22 | 2024-08-14 | 길리애드 사이언시즈, 인코포레이티드 | 이카로스 아연 핑거 패밀리 분해제 및 이의 용도 |
| TW202340168A (zh) | 2022-01-28 | 2023-10-16 | 美商基利科學股份有限公司 | Ｐａｒｐ７抑制劑 |
| WO2023178181A1 (en) | 2022-03-17 | 2023-09-21 | Gilead Sciences, Inc. | Ikaros zinc finger family degraders and uses thereof |
| KR20240165995A (ko) | 2022-03-24 | 2024-11-25 | 길리애드 사이언시즈, 인코포레이티드 | Trop-2 발현 암의 치료를 위한 병용요법 |
| 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 |
| KR20250028371A (ko) | 2022-07-01 | 2025-02-28 | 길리애드 사이언시즈, 인코포레이티드 | Cd73 화합물 |
| WO2024064668A1 (en) | 2022-09-21 | 2024-03-28 | Gilead Sciences, Inc. | FOCAL IONIZING RADIATION AND CD47/SIRPα DISRUPTION ANTICANCER COMBINATION THERAPY |
| AU2023409398A1 (en) | 2022-12-22 | 2025-06-05 | Gilead Sciences, Inc. | Prmt5 inhibitors and uses thereof |
| 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 |
| CR20250446A (es) | 2023-04-21 | 2025-12-02 | 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 |
| CN121620513A (zh) | 2023-07-26 | 2026-03-06 | 吉利德科学公司 | Parp7抑制剂 |
| KR20260046403A (ko) | 2023-07-26 | 2026-04-07 | 길리애드 사이언시즈, 인코포레이티드 | Parp7 저해제 |
| US20250109147A1 (en) | 2023-09-08 | 2025-04-03 | Gilead Sciences, Inc. | Kras g12d modulating compounds |
| US20250101042A1 (en) | 2023-09-08 | 2025-03-27 | Gilead Sciences, Inc. | 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 |
| US20260098049A1 (en) | 2024-08-12 | 2026-04-09 | Gilead Sciences, Inc. | Kras modulating compounds |
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 |
| MX353308B (es) | 2008-05-21 | 2018-01-08 | Ariad Pharma Inc | Derivados fosforosos como inhibidores de cinasa. |
| WO2012051587A1 (en) | 2010-10-14 | 2012-04-19 | 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 |
| CA2932353A1 (en) * | 2013-12-13 | 2015-06-18 | Steven P. Treon | Methods to treat lymphoplasmacytic lymphoma |
| EP3159338A4 (en) | 2014-06-17 | 2018-01-24 | Korea Research Institute of Chemical Technology | Pyrimidine-2,4-diamine derivative and anticancer pharmaceutical composition comprising same as effective ingredient |
-
2017
- 2017-11-29 WO PCT/US2017/063633 patent/WO2018102366A1/en not_active Ceased
- 2017-11-29 MA MA046942A patent/MA46942A/fr unknown
- 2017-11-29 EP EP17811814.7A patent/EP3548479A1/en not_active Withdrawn
- 2017-11-29 JP JP2019528807A patent/JP7025426B2/ja active Active
- 2017-11-29 US US16/465,073 patent/US11180482B2/en active Active
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP2020503271A5 (https=) | ||
| CN114430739A (zh) | Egfr抑制剂、组合物及其制备方法 | |
| SI3074386T1 (en) | New aminopyrimidine derivatives | |
| RU2016103938A (ru) | Модуляторы протеин-тирозинкиназы и способы их применения | |
| IL271291B2 (en) | History of n2,n4-diphenylpyrimidine-2,4-diamine, a method for their preparation, and a pharmaceutical preparation containing them as an active ingredient for the prevention or treatment of cancer | |
| CA2577937A1 (en) | Pyrazole-substituted aminoheteroaryl compounds as protein kinase inhibitors | |
| JP2018012712A5 (https=) | ||
| PE20090493A1 (es) | DERIVADOS DE LA 6-CICLOAMINO-3-(PIRIDAZIN-4-IL)IMIDAZO[1,2-b]-PIRIDAZINA, SU PREPARACION Y SU APLICACION EN TERAPEUTICA | |
| JP2020524719A5 (https=) | ||
| JP2014513110A5 (https=) | ||
| JP2007517807A5 (https=) | ||
| JP2011509309A5 (https=) | ||
| JP2016514717A5 (https=) | ||
| RU2016134751A (ru) | Соединения | |
| JP2016538313A5 (https=) | ||
| JP2016106095A (ja) | イミダゾピロリジノン化合物 | |
| JP2016514719A5 (https=) | ||
| ME02630B (me) | Makrociklički derivati, namijenjeni liječenju proliferativnih bolesti | |
| JP2016525076A5 (https=) | ||
| AR077468A1 (es) | Compuestos de pirazolo (1,5 -a) pirimidina sustituidos como inhibidores de trk- quinasa | |
| JP2009520685A5 (https=) | ||
| JP2014525432A5 (https=) | ||
| JP2009538897A5 (https=) | ||
| JP2018507899A5 (https=) | ||
| JP2013538811A5 (https=) |