JP6510510B2 - プロテインチロシンキナーゼモジュレーター及び使用方法 - Google Patents

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Publication number

JP6510510B2

JP6510510B2 JP2016524675A JP2016524675A JP6510510B2 JP 6510510 B2 JP6510510 B2 JP 6510510B2 JP 2016524675 A JP2016524675 A JP 2016524675A JP 2016524675 A JP2016524675 A JP 2016524675A JP 6510510 B2 JP6510510 B2 JP 6510510B2

Authority

JP

Japan

Prior art keywords

pyrimidin

chloro

phenyl

ylamino

dimethylamino

Prior art date

2013-07-11

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.)

Expired - Fee Related

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• 238000000034 method Methods 0.000 title description 25
• 102000004022 Protein-Tyrosine Kinases Human genes 0.000 title description 4
• 108090000412 Protein-Tyrosine Kinases Proteins 0.000 title description 4
• 150000001875 compounds Chemical class 0.000 claims description 189
• -1 -O-heterocycle Chemical group 0.000 claims description 131
• 125000000217 alkyl group Chemical group 0.000 claims description 64
• 206010028980 Neoplasm Diseases 0.000 claims description 59
• 102100033793 ALK tyrosine kinase receptor Human genes 0.000 claims description 54
• 101710168331 ALK tyrosine kinase receptor Proteins 0.000 claims description 51
• 201000011510 cancer Diseases 0.000 claims description 45
• 125000000623 heterocyclic group Chemical group 0.000 claims description 44
• 229910052736 halogen Inorganic materials 0.000 claims description 38
• HRPVXLWXLXDGHG-UHFFFAOYSA-N Acrylamide Chemical compound NC(=O)C=C HRPVXLWXLXDGHG-UHFFFAOYSA-N 0.000 claims description 32
• 125000003545 alkoxy group Chemical group 0.000 claims description 32
• 150000002367 halogens Chemical group 0.000 claims description 31
• 108091000080 Phosphotransferase Proteins 0.000 claims description 30
• 102000020233 phosphotransferase Human genes 0.000 claims description 30
• 150000003839 salts Chemical class 0.000 claims description 30
• CYRMSUTZVYGINF-UHFFFAOYSA-N trichlorofluoromethane Chemical compound FC(Cl)(Cl)Cl CYRMSUTZVYGINF-UHFFFAOYSA-N 0.000 claims description 28
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 27
• 230000035772 mutation Effects 0.000 claims description 25
• 208000002154 non-small cell lung carcinoma Diseases 0.000 claims description 25
• 208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 claims description 25
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 24
• 125000003342 alkenyl group Chemical group 0.000 claims description 23
• 229910052739 hydrogen Inorganic materials 0.000 claims description 22
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 20
• 239000008194 pharmaceutical composition Substances 0.000 claims description 20
• 125000004404 heteroalkyl group Chemical group 0.000 claims description 18
• 229910052799 carbon Inorganic materials 0.000 claims description 17
• 239000003814 drug Substances 0.000 claims description 17
• 125000003118 aryl group Chemical group 0.000 claims description 16
• XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 15
• 125000000304 alkynyl group Chemical group 0.000 claims description 14
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 14
• 125000000000 cycloalkoxy group Chemical group 0.000 claims description 13
• 102000037865 fusion proteins Human genes 0.000 claims description 13
• 108020001507 fusion proteins Proteins 0.000 claims description 13
• 125000001072 heteroaryl group Chemical group 0.000 claims description 13
• 125000005842 heteroatom Chemical group 0.000 claims description 13
• 125000004070 6 membered heterocyclic group Chemical group 0.000 claims description 12
• 201000010099 disease Diseases 0.000 claims description 12
• 238000011282 treatment Methods 0.000 claims description 12
• 125000001188 haloalkyl group Chemical group 0.000 claims description 11
• 229910052760 oxygen Inorganic materials 0.000 claims description 10
• 239000001257 hydrogen Substances 0.000 claims description 9
• 229910052757 nitrogen Inorganic materials 0.000 claims description 9
• 125000002373 5 membered heterocyclic group Chemical group 0.000 claims description 8
• 206010006187 Breast cancer Diseases 0.000 claims description 8
• 208000026310 Breast neoplasm Diseases 0.000 claims description 8
• 208000001333 Colorectal Neoplasms Diseases 0.000 claims description 7
• 125000002837 carbocyclic group Chemical group 0.000 claims description 7
• 125000000392 cycloalkenyl group Chemical group 0.000 claims description 7
• 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 6
• 206010009944 Colon cancer Diseases 0.000 claims description 6
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 6
• 206010061902 Pancreatic neoplasm Diseases 0.000 claims description 6
• 125000003302 alkenyloxy group Chemical group 0.000 claims description 6
• 238000012217 deletion Methods 0.000 claims description 6
• 230000037430 deletion Effects 0.000 claims description 6
• 208000005017 glioblastoma Diseases 0.000 claims description 6
• 208000015486 malignant pancreatic neoplasm Diseases 0.000 claims description 6
• 208000008443 pancreatic carcinoma Diseases 0.000 claims description 6
• 208000024172 Cardiovascular disease Diseases 0.000 claims description 5
• 206010027476 Metastases Diseases 0.000 claims description 5
• 101100335081 Mus musculus Flt3 gene Proteins 0.000 claims description 5
• 206010060862 Prostate cancer Diseases 0.000 claims description 5
• 208000000236 Prostatic Neoplasms Diseases 0.000 claims description 5
• 208000009956 adenocarcinoma Diseases 0.000 claims description 5
• 208000026278 immune system disease Diseases 0.000 claims description 5
• 230000009401 metastasis Effects 0.000 claims description 5
• 201000002528 pancreatic cancer Diseases 0.000 claims description 5
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 5
• 229910052717 sulfur Inorganic materials 0.000 claims description 5
• 101001012157 Homo sapiens Receptor tyrosine-protein kinase erbB-2 Proteins 0.000 claims description 4
• 101150069380 JAK3 gene Proteins 0.000 claims description 4
• WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 claims description 4
• 101100381649 Mus musculus Bik gene Proteins 0.000 claims description 4
• 101100381845 Mus musculus Blk gene Proteins 0.000 claims description 4
• 101100272634 Mus musculus Bmx gene Proteins 0.000 claims description 4
• 206010033128 Ovarian cancer Diseases 0.000 claims description 4
• 206010061535 Ovarian neoplasm Diseases 0.000 claims description 4
• 102100030086 Receptor tyrosine-protein kinase erbB-2 Human genes 0.000 claims description 4
• 102100029981 Receptor tyrosine-protein kinase erbB-4 Human genes 0.000 claims description 4
• 101710100963 Receptor tyrosine-protein kinase erbB-4 Proteins 0.000 claims description 4
• 125000004429 atom Chemical group 0.000 claims description 4
• 229910052731 fluorine Inorganic materials 0.000 claims description 4
• 239000000546 pharmaceutical excipient Substances 0.000 claims description 4
• GVNVAWHJIKLAGL-UHFFFAOYSA-N 2-(cyclohexen-1-yl)cyclohexan-1-one Chemical compound O=C1CCCCC1C1=CCCCC1 GVNVAWHJIKLAGL-UHFFFAOYSA-N 0.000 claims description 3
• 239000004475 Arginine Substances 0.000 claims description 3
• 201000009030 Carcinoma Diseases 0.000 claims description 3
• 101150065749 Churc1 gene Proteins 0.000 claims description 3
• 102100038239 Protein Churchill Human genes 0.000 claims description 3
• 125000002490 anilino group Chemical group [H]N(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 3
• ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 claims description 3
• 125000003710 aryl alkyl group Chemical group 0.000 claims description 3
• 229920001577 copolymer Chemical group 0.000 claims description 3
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 3
• 208000030533 eye disease Diseases 0.000 claims description 3
• 150000002431 hydrogen Chemical class 0.000 claims description 3
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 3
• 230000002265 prevention Effects 0.000 claims description 3
• 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 claims description 3
• 229920002554 vinyl polymer Chemical group 0.000 claims description 3
• ILLYKAKXONHJRD-RMKNXTFCSA-N (e)-n-[3-[[5-chloro-4-[2-[2-(dimethylamino)-2-oxoacetyl]anilino]pyrimidin-2-yl]amino]-4-methoxyphenyl]-4-morpholin-4-ylbut-2-enamide Chemical compound C1=C(NC=2N=C(NC=3C(=CC=CC=3)C(=O)C(=O)N(C)C)C(Cl)=CN=2)C(OC)=CC=C1NC(=O)\C=C\CN1CCOCC1 ILLYKAKXONHJRD-RMKNXTFCSA-N 0.000 claims description 2
• RWVBCVGNYVHDIE-VMPITWQZSA-N (e)-n-[3-[[5-chloro-4-[2-[2-(dimethylamino)-2-oxoacetyl]anilino]pyrimidin-2-yl]amino]-4-methoxyphenyl]but-2-enamide Chemical compound COC1=CC=C(NC(=O)\C=C\C)C=C1NC1=NC=C(Cl)C(NC=2C(=CC=CC=2)C(=O)C(=O)N(C)C)=N1 RWVBCVGNYVHDIE-VMPITWQZSA-N 0.000 claims description 2
• PVOAHINGSUIXLS-UHFFFAOYSA-N 1-Methylpiperazine Chemical compound CN1CCNCC1 PVOAHINGSUIXLS-UHFFFAOYSA-N 0.000 claims description 2
• FRRCZEINUNMNNX-UHFFFAOYSA-N 1-[2-[[2-[2-methoxy-4-(4-methylpiperazin-1-yl)anilino]-5-(trifluoromethyl)pyrimidin-4-yl]amino]phenyl]-2-morpholin-4-ylethane-1,2-dione Chemical compound COC1=CC(N2CCN(C)CC2)=CC=C1NC(N=1)=NC=C(C(F)(F)F)C=1NC1=CC=CC=C1C(=O)C(=O)N1CCOCC1 FRRCZEINUNMNNX-UHFFFAOYSA-N 0.000 claims description 2
• HGXZFEHOKFOTQQ-UHFFFAOYSA-N 1-[2-[[2-[4-(4-acetylpiperazin-1-yl)-2-methoxyanilino]-5-chloropyrimidin-4-yl]amino]phenyl]-2-morpholin-4-ylethane-1,2-dione Chemical compound COC1=CC(N2CCN(CC2)C(C)=O)=CC=C1NC(N=1)=NC=C(Cl)C=1NC1=CC=CC=C1C(=O)C(=O)N1CCOCC1 HGXZFEHOKFOTQQ-UHFFFAOYSA-N 0.000 claims description 2
• OOURWTXSGRFQDW-UHFFFAOYSA-N 1-[2-[[2-[4-[4-(dimethylamino)piperidin-1-yl]-2-methoxyanilino]-5-(trifluoromethyl)pyrimidin-4-yl]amino]phenyl]-2-morpholin-4-ylethane-1,2-dione Chemical compound COC1=CC(N2CCC(CC2)N(C)C)=CC=C1NC(N=1)=NC=C(C(F)(F)F)C=1NC1=CC=CC=C1C(=O)C(=O)N1CCOCC1 OOURWTXSGRFQDW-UHFFFAOYSA-N 0.000 claims description 2
• MMCUGRPNLUIXRH-UHFFFAOYSA-N 1-[2-[[5-chloro-2-[2-methoxy-4-(4-methylpiperazin-1-yl)anilino]pyrimidin-4-yl]amino]phenyl]-2-morpholin-4-ylethane-1,2-dione Chemical compound COC1=CC(N2CCN(C)CC2)=CC=C1NC(N=1)=NC=C(Cl)C=1NC1=CC=CC=C1C(=O)C(=O)N1CCOCC1 MMCUGRPNLUIXRH-UHFFFAOYSA-N 0.000 claims description 2
• XOOXHSGUXZVMHW-UHFFFAOYSA-N 2-[2-[[2-[2-methoxy-4-(4-methylpiperazin-1-yl)anilino]-5-(trifluoromethyl)pyrimidin-4-yl]amino]phenyl]-2-oxoacetamide Chemical compound COC1=CC(N2CCN(C)CC2)=CC=C1NC(N=1)=NC=C(C(F)(F)F)C=1NC1=CC=CC=C1C(=O)C(N)=O XOOXHSGUXZVMHW-UHFFFAOYSA-N 0.000 claims description 2
• RKRWLTRLAVJFEK-UHFFFAOYSA-N 2-[2-[[2-[4-(4-acetylpiperazin-1-yl)-2-methoxyanilino]-5-chloropyrimidin-4-yl]amino]phenyl]-n-cyclopropyl-2-oxoacetamide Chemical compound COC1=CC(N2CCN(CC2)C(C)=O)=CC=C1NC(N=1)=NC=C(Cl)C=1NC1=CC=CC=C1C(=O)C(=O)NC1CC1 RKRWLTRLAVJFEK-UHFFFAOYSA-N 0.000 claims description 2
• OPGVLJXVFJLLDZ-UHFFFAOYSA-N 2-[2-[[2-[4-[4-(dimethylamino)piperidin-1-yl]-2-methoxyanilino]-5-(trifluoromethyl)pyrimidin-4-yl]amino]phenyl]-2-oxoacetic acid Chemical compound COC1=CC(N2CCC(CC2)N(C)C)=CC=C1NC(N=1)=NC=C(C(F)(F)F)C=1NC1=CC=CC=C1C(=O)C(O)=O OPGVLJXVFJLLDZ-UHFFFAOYSA-N 0.000 claims description 2
• LAQSBYOOKAWFSV-UHFFFAOYSA-N 2-[2-[[2-[4-[[1-(2-fluoroethyl)azetidin-3-yl]amino]-2-methoxyanilino]-5-(trifluoromethyl)pyrimidin-4-yl]amino]phenyl]-2-oxoacetamide Chemical compound C=1C=C(NC=2N=C(NC=3C(=CC=CC=3)C(=O)C(N)=O)C(=CN=2)C(F)(F)F)C(OC)=CC=1NC1CN(CCF)C1 LAQSBYOOKAWFSV-UHFFFAOYSA-N 0.000 claims description 2
• AERYPYJUMMERSC-UHFFFAOYSA-N 2-[2-[[5-chloro-2-(2-methoxy-4-morpholin-4-ylanilino)pyrimidin-4-yl]amino]phenyl]-n,n-dimethyl-2-oxoacetamide Chemical compound COC1=CC(N2CCOCC2)=CC=C1NC(N=1)=NC=C(Cl)C=1NC1=CC=CC=C1C(=O)C(=O)N(C)C AERYPYJUMMERSC-UHFFFAOYSA-N 0.000 claims description 2
• RSIQSLXNWUEYCL-UHFFFAOYSA-N 2-[2-[[5-chloro-2-(2-methoxy-4-morpholin-4-ylanilino)pyrimidin-4-yl]amino]phenyl]-n-cyclopropyl-2-oxoacetamide Chemical compound COC1=CC(N2CCOCC2)=CC=C1NC(N=1)=NC=C(Cl)C=1NC1=CC=CC=C1C(=O)C(=O)NC1CC1 RSIQSLXNWUEYCL-UHFFFAOYSA-N 0.000 claims description 2
• YPHMDPDDBHBKPH-UHFFFAOYSA-N 2-[2-[[5-chloro-2-(2-methoxy-4-piperidin-4-ylanilino)pyrimidin-4-yl]amino]phenyl]prop-2-enoic acid Chemical compound COC1=CC(C2CCNCC2)=CC=C1NC(N=1)=NC=C(Cl)C=1NC1=CC=CC=C1C(=C)C(O)=O YPHMDPDDBHBKPH-UHFFFAOYSA-N 0.000 claims description 2
• CUOFJQAAYKJYJM-UHFFFAOYSA-N 2-[2-[[5-chloro-2-(4-fluoro-3-methoxyanilino)pyrimidin-4-yl]amino]phenyl]-n,n-dimethyl-2-oxoacetamide Chemical compound C1=C(F)C(OC)=CC(NC=2N=C(NC=3C(=CC=CC=3)C(=O)C(=O)N(C)C)C(Cl)=CN=2)=C1 CUOFJQAAYKJYJM-UHFFFAOYSA-N 0.000 claims description 2
• FWPFRLAKYIVTFY-UHFFFAOYSA-N 2-[2-[[5-chloro-2-(4-fluoro-3-methoxyanilino)pyrimidin-4-yl]amino]phenyl]-n-methyl-2-oxoacetamide Chemical compound CNC(=O)C(=O)C1=CC=CC=C1NC1=NC(NC=2C=C(OC)C(F)=CC=2)=NC=C1Cl FWPFRLAKYIVTFY-UHFFFAOYSA-N 0.000 claims description 2
• KXPICMSXZCNILY-UHFFFAOYSA-N 2-[2-[[5-chloro-2-[(4-prop-2-enoyl-2,3-dihydro-1,4-benzoxazin-6-yl)amino]pyrimidin-4-yl]amino]phenyl]-n,n-dimethyl-2-oxoacetamide Chemical compound CN(C)C(=O)C(=O)C1=CC=CC=C1NC1=NC(NC=2C=C3N(C(=O)C=C)CCOC3=CC=2)=NC=C1Cl KXPICMSXZCNILY-UHFFFAOYSA-N 0.000 claims description 2
• WHAGLQJWJWUYFE-UHFFFAOYSA-N 2-[2-[[5-chloro-2-[2-methoxy-4-(4-methylpiperazin-1-yl)anilino]pyrimidin-4-yl]amino]phenyl]-2-oxo-n-(1-prop-2-enoylpiperidin-4-yl)acetamide Chemical compound COC1=CC(N2CCN(C)CC2)=CC=C1NC(N=1)=NC=C(Cl)C=1NC1=CC=CC=C1C(=O)C(=O)NC1CCN(C(=O)C=C)CC1 WHAGLQJWJWUYFE-UHFFFAOYSA-N 0.000 claims description 2
• XINCMWVRVWORPO-UHFFFAOYSA-N 2-[2-[[5-chloro-2-[2-methoxy-4-(4-methylpiperazin-1-yl)anilino]pyrimidin-4-yl]amino]phenyl]-n-cyclopropyl-2-oxoacetamide Chemical compound COC1=CC(N2CCN(C)CC2)=CC=C1NC(N=1)=NC=C(Cl)C=1NC1=CC=CC=C1C(=O)C(=O)NC1CC1 XINCMWVRVWORPO-UHFFFAOYSA-N 0.000 claims description 2
• XACHZVJBZTVCPK-UHFFFAOYSA-N 2-[2-[[5-chloro-2-[2-methoxy-4-(4-methylpiperazin-1-yl)anilino]pyrimidin-4-yl]amino]phenyl]prop-2-enoic acid Chemical compound COC1=CC(N2CCN(C)CC2)=CC=C1NC(N=1)=NC=C(Cl)C=1NC1=CC=CC=C1C(=C)C(O)=O XACHZVJBZTVCPK-UHFFFAOYSA-N 0.000 claims description 2
• BJFDBMNLCPJVHU-UHFFFAOYSA-N 2-[2-[[5-chloro-2-[2-methoxy-4-[4-(methylamino)piperidin-1-yl]anilino]pyrimidin-4-yl]amino]phenyl]-n-(2-hydroxyethyl)-2-oxoacetamide Chemical compound C1CC(NC)CCN1C(C=C1OC)=CC=C1NC1=NC=C(Cl)C(NC=2C(=CC=CC=2)C(=O)C(=O)NCCO)=N1 BJFDBMNLCPJVHU-UHFFFAOYSA-N 0.000 claims description 2
• DIQHRPNVYBPCQW-UHFFFAOYSA-N 2-[2-[[5-chloro-2-[3-methoxy-4-(4-methylpiperazin-1-yl)anilino]pyrimidin-4-yl]amino]phenyl]-n,n-dimethyl-2-oxoacetamide Chemical compound C=1C=C(N2CCN(C)CC2)C(OC)=CC=1NC(N=1)=NC=C(Cl)C=1NC1=CC=CC=C1C(=O)C(=O)N(C)C DIQHRPNVYBPCQW-UHFFFAOYSA-N 0.000 claims description 2
• AMSONZZHZCNUHV-UHFFFAOYSA-N 2-[2-[[5-chloro-2-[4-[4-(dimethylamino)piperidin-1-yl]-2-methoxyanilino]pyrimidin-4-yl]amino]phenyl]-2-oxoacetamide Chemical compound COC1=CC(N2CCC(CC2)N(C)C)=CC=C1NC(N=1)=NC=C(Cl)C=1NC1=CC=CC=C1C(=O)C(N)=O AMSONZZHZCNUHV-UHFFFAOYSA-N 0.000 claims description 2
• KTONNTOWXWZRTD-UHFFFAOYSA-N 2-[2-[[5-chloro-2-[4-[4-(dimethylamino)piperidin-1-yl]-2-methoxyanilino]pyrimidin-4-yl]amino]phenyl]-2-oxoacetic acid Chemical compound COC1=CC(N2CCC(CC2)N(C)C)=CC=C1NC(N=1)=NC=C(Cl)C=1NC1=CC=CC=C1C(=O)C(O)=O KTONNTOWXWZRTD-UHFFFAOYSA-N 0.000 claims description 2
• MYIWVWKTSMMMKQ-UHFFFAOYSA-N 2-[2-[[5-chloro-2-[4-[4-(dimethylamino)piperidin-1-yl]-2-methoxyanilino]pyrimidin-4-yl]amino]phenyl]-n,n-dimethyl-2-oxoacetamide Chemical compound COC1=CC(N2CCC(CC2)N(C)C)=CC=C1NC(N=1)=NC=C(Cl)C=1NC1=CC=CC=C1C(=O)C(=O)N(C)C MYIWVWKTSMMMKQ-UHFFFAOYSA-N 0.000 claims description 2
• CPYWRIFWULRBFC-UHFFFAOYSA-N 2-[2-[[5-chloro-2-[4-[4-(dimethylamino)piperidin-1-yl]-2-methoxyanilino]pyrimidin-4-yl]amino]phenyl]-n-cyclopropyl-2-oxoacetamide Chemical compound COC1=CC(N2CCC(CC2)N(C)C)=CC=C1NC(N=1)=NC=C(Cl)C=1NC1=CC=CC=C1C(=O)C(=O)NC1CC1 CPYWRIFWULRBFC-UHFFFAOYSA-N 0.000 claims description 2
• JLFPEHXJEYWJFT-UHFFFAOYSA-N 2-[2-[[5-chloro-2-[4-[4-(dimethylamino)piperidin-1-yl]-2-methoxyanilino]pyrimidin-4-yl]amino]phenyl]-n-hydroxy-2-oxoacetamide Chemical compound COC1=CC(N2CCC(CC2)N(C)C)=CC=C1NC(N=1)=NC=C(Cl)C=1NC1=CC=CC=C1C(=O)C(=O)NO JLFPEHXJEYWJFT-UHFFFAOYSA-N 0.000 claims description 2
• YAJAQZIBHSVGQC-UHFFFAOYSA-N 2-[2-[[5-chloro-2-[4-[[1-(2-fluoroethyl)azetidin-3-yl]amino]-2-methoxyanilino]pyrimidin-4-yl]amino]phenyl]-2-oxoacetamide Chemical compound C=1C=C(NC=2N=C(NC=3C(=CC=CC=3)C(=O)C(N)=O)C(Cl)=CN=2)C(OC)=CC=1NC1CN(CCF)C1 YAJAQZIBHSVGQC-UHFFFAOYSA-N 0.000 claims description 2
• PHGJBYINNNRCCL-UHFFFAOYSA-N 2-[2-[[5-chloro-2-[4-[[1-(2-fluoroethyl)azetidin-3-yl]amino]-2-methoxyanilino]pyrimidin-4-yl]amino]phenyl]prop-2-enoic acid Chemical compound C=1C=C(NC=2N=C(NC=3C(=CC=CC=3)C(=C)C(O)=O)C(Cl)=CN=2)C(OC)=CC=1NC1CN(CCF)C1 PHGJBYINNNRCCL-UHFFFAOYSA-N 0.000 claims description 2
• 125000001627 3 membered heterocyclic group Chemical group 0.000 claims description 2
• 125000001963 4 membered heterocyclic group Chemical group 0.000 claims description 2
• 125000003341 7 membered heterocyclic group Chemical group 0.000 claims description 2
• 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 2
• JDNLUZNUMAVAJW-UHFFFAOYSA-N CCCOc1ccc(Nc2ncc(Cl)c(Nc3ccccc3C(=O)C(=O)N(C)C)n2)cc1NC(=O)C=C Chemical compound CCCOc1ccc(Nc2ncc(Cl)c(Nc3ccccc3C(=O)C(=O)N(C)C)n2)cc1NC(=O)C=C JDNLUZNUMAVAJW-UHFFFAOYSA-N 0.000 claims description 2
• OWBOSFMMDBVZFQ-UHFFFAOYSA-N CN(C)C(=O)C(=O)c1ccccc1Nc1nc(Nc2ccc(OC(F)F)c(NC(=O)C=C)c2)ncc1Cl Chemical compound CN(C)C(=O)C(=O)c1ccccc1Nc1nc(Nc2ccc(OC(F)F)c(NC(=O)C=C)c2)ncc1Cl OWBOSFMMDBVZFQ-UHFFFAOYSA-N 0.000 claims description 2
• NBSGAVFJNFMDSN-UHFFFAOYSA-N CN(C)C(=O)C(=O)c1ccccc1Nc1nc(Nc2ccc(OC3CCOC3)c(NC(=O)C=C)c2)ncc1Cl Chemical compound CN(C)C(=O)C(=O)c1ccccc1Nc1nc(Nc2ccc(OC3CCOC3)c(NC(=O)C=C)c2)ncc1Cl NBSGAVFJNFMDSN-UHFFFAOYSA-N 0.000 claims description 2
• OPTXICWCRDMSMG-UHFFFAOYSA-N CN(C)CCCc1ccc(Nc2ncc(Cl)c(Nc3ccccc3C(=O)C(=O)N(C)C)n2)cc1NC(=O)C=C Chemical compound CN(C)CCCc1ccc(Nc2ncc(Cl)c(Nc3ccccc3C(=O)C(=O)N(C)C)n2)cc1NC(=O)C=C OPTXICWCRDMSMG-UHFFFAOYSA-N 0.000 claims description 2
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