AU2014289762B2 - Protein tyrosine kinase modulators and methods of use - Google Patents

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Publication number

AU2014289762B2

AU2014289762B2 AU2014289762A AU2014289762A AU2014289762B2 AU 2014289762 B2 AU2014289762 B2 AU 2014289762B2 AU 2014289762 A AU2014289762 A AU 2014289762A AU 2014289762 A AU2014289762 A AU 2014289762A AU 2014289762 B2 AU2014289762 B2 AU 2014289762B2

Authority

AU

Australia

Prior art keywords

chloro

phenyl

pyrimidin

dimethylamino

ylamino

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.)

Ceased

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• 238000000034 method Methods 0.000 title claims abstract description 35
• 102000004022 Protein-Tyrosine Kinases Human genes 0.000 title description 5
• 108090000412 Protein-Tyrosine Kinases Proteins 0.000 title description 5
• -1 Heterocyclic pyrimidine compounds Chemical class 0.000 claims abstract description 58
• 102100033793 ALK tyrosine kinase receptor Human genes 0.000 claims abstract description 57
• 101710168331 ALK tyrosine kinase receptor Proteins 0.000 claims abstract description 50
• 208000002154 non-small cell lung carcinoma Diseases 0.000 claims abstract description 29
• 108091000080 Phosphotransferase Proteins 0.000 claims abstract description 27
• 102000020233 phosphotransferase Human genes 0.000 claims abstract description 27
• 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 25
• 238000011282 treatment Methods 0.000 claims abstract description 17
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 13
• 201000010099 disease Diseases 0.000 claims abstract description 12
• 208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 claims abstract description 10
• 150000001875 compounds Chemical class 0.000 claims description 208
• 229910052736 halogen Inorganic materials 0.000 claims description 59
• 206010028980 Neoplasm Diseases 0.000 claims description 57
• 150000002367 halogens Chemical group 0.000 claims description 54
• 125000000623 heterocyclic group Chemical group 0.000 claims description 49
• 102200048955 rs121434569 Human genes 0.000 claims description 49
• 201000011510 cancer Diseases 0.000 claims description 42
• 125000000217 alkyl group Chemical group 0.000 claims description 39
• 150000003839 salts Chemical class 0.000 claims description 30
• 125000003545 alkoxy group Chemical group 0.000 claims description 29
• 102200048928 rs121434568 Human genes 0.000 claims description 29
• 230000035772 mutation Effects 0.000 claims description 27
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 26
• 125000001188 haloalkyl group Chemical group 0.000 claims description 22
• 125000003342 alkenyl group Chemical group 0.000 claims description 21
• 125000004404 heteroalkyl group Chemical group 0.000 claims description 20
• 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 16
• 125000003118 aryl group Chemical group 0.000 claims description 16
• 102000037865 fusion proteins Human genes 0.000 claims description 13
• 108020001507 fusion proteins Proteins 0.000 claims description 13
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 13
• 125000001072 heteroaryl group Chemical group 0.000 claims description 12
• 125000005842 heteroatom Chemical group 0.000 claims description 12
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 12
• 125000000000 cycloalkoxy group Chemical group 0.000 claims description 11
• 208000014829 head and neck neoplasm Diseases 0.000 claims description 11
• 230000002401 inhibitory effect Effects 0.000 claims description 11
• HRPVXLWXLXDGHG-UHFFFAOYSA-N Acrylamide Chemical compound NC(=O)C=C HRPVXLWXLXDGHG-UHFFFAOYSA-N 0.000 claims description 10
• 125000002837 carbocyclic group Chemical group 0.000 claims description 10
• 229910052739 hydrogen Inorganic materials 0.000 claims description 10
• 208000009956 adenocarcinoma Diseases 0.000 claims description 9
• 125000000304 alkynyl group Chemical group 0.000 claims description 9
• 239000003814 drug Substances 0.000 claims description 9
• 201000010536 head and neck cancer Diseases 0.000 claims description 9
• 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 8
• 206010061902 Pancreatic neoplasm Diseases 0.000 claims description 7
• 208000005017 glioblastoma Diseases 0.000 claims description 7
• 239000001257 hydrogen Substances 0.000 claims description 7
• 208000015486 malignant pancreatic neoplasm Diseases 0.000 claims description 7
• 229910052757 nitrogen Inorganic materials 0.000 claims description 7
• 201000002528 pancreatic cancer Diseases 0.000 claims description 7
• 208000008443 pancreatic carcinoma Diseases 0.000 claims description 7
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 7
• 238000002360 preparation method Methods 0.000 claims description 7
• 206010009944 Colon cancer Diseases 0.000 claims description 6
• 206010060862 Prostate cancer Diseases 0.000 claims description 6
• 208000000236 Prostatic Neoplasms Diseases 0.000 claims description 6
• 208000000102 Squamous Cell Carcinoma of Head and Neck Diseases 0.000 claims description 6
• 125000000392 cycloalkenyl group Chemical group 0.000 claims description 6
• 201000000459 head and neck squamous cell carcinoma Diseases 0.000 claims description 6
• 201000009030 Carcinoma Diseases 0.000 claims description 5
• 206010033128 Ovarian cancer Diseases 0.000 claims description 5
• 206010061535 Ovarian neoplasm Diseases 0.000 claims description 5
• 125000004429 atom Chemical group 0.000 claims description 4
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 4
• 229910052760 oxygen Inorganic materials 0.000 claims description 4
• 239000000546 pharmaceutical excipient Substances 0.000 claims description 4
• 206010041823 squamous cell carcinoma Diseases 0.000 claims description 4
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 3
• 206010027476 Metastases Diseases 0.000 claims description 3
• 125000003302 alkenyloxy group Chemical group 0.000 claims description 3
• 229910052731 fluorine Inorganic materials 0.000 claims description 3
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 3
• 230000009401 metastasis Effects 0.000 claims description 3
• VMFMUJZRXZXYAH-UHFFFAOYSA-N n-[5-[[5-chloro-4-[2-[2-(dimethylamino)-2-oxoacetyl]anilino]pyrimidin-2-yl]amino]-4-methoxy-2-(4-methylpiperazin-1-yl)phenyl]prop-2-enamide Chemical compound C=CC(=O)NC=1C=C(NC=2N=C(NC=3C(=CC=CC=3)C(=O)C(=O)N(C)C)C(Cl)=CN=2)C(OC)=CC=1N1CCN(C)CC1 VMFMUJZRXZXYAH-UHFFFAOYSA-N 0.000 claims description 3
• 230000002265 prevention Effects 0.000 claims description 3
• 229910052717 sulfur Inorganic materials 0.000 claims description 3
• PJFDVBGAJCVKJT-UHFFFAOYSA-N 2-(azetidin-1-ylmethyl)-n-[3-[[5-chloro-4-[2-[2-(dimethylamino)-2-oxoacetyl]anilino]pyrimidin-2-yl]amino]-4-methoxyphenyl]prop-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)CN1CCC1 PJFDVBGAJCVKJT-UHFFFAOYSA-N 0.000 claims description 2
• FOUKQAHZOQZGDF-UHFFFAOYSA-N 2-(aziridin-1-ylmethyl)-n-[3-[[5-chloro-4-[2-[2-(dimethylamino)-2-oxoacetyl]anilino]pyrimidin-2-yl]amino]-4-methoxyphenyl]prop-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)CN1CC1 FOUKQAHZOQZGDF-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
• VAZJPWRFIIAFOG-UHFFFAOYSA-N 2-[2-[[2-[4-(4-acetylpiperazin-1-yl)-2-methoxyanilino]-5-chloropyrimidin-4-yl]amino]phenyl]-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(N)=O VAZJPWRFIIAFOG-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
• DCYQQOSGSUVQOP-UHFFFAOYSA-N 2-[2-[[5-chloro-2-(5-methyl-4-piperidin-4-yl-2-propan-2-yloxyanilino)pyrimidin-4-yl]amino]phenyl]-2-oxoacetamide Chemical compound CC=1C=C(NC=2N=C(NC=3C(=CC=CC=3)C(=O)C(N)=O)C(Cl)=CN=2)C(OC(C)C)=CC=1C1CCNCC1 DCYQQOSGSUVQOP-UHFFFAOYSA-N 0.000 claims description 2
• MVLGFIGPCZYXSX-UHFFFAOYSA-N 2-[2-[[5-chloro-2-[2-methoxy-4-(1-methylpiperidin-4-yl)anilino]pyrimidin-4-yl]amino]phenyl]prop-2-enoic acid Chemical compound COC1=CC(C2CCN(C)CC2)=CC=C1NC(N=1)=NC=C(Cl)C=1NC1=CC=CC=C1C(=C)C(O)=O MVLGFIGPCZYXSX-UHFFFAOYSA-N 0.000 claims description 2
• ZYWWKSPNANEDRB-UHFFFAOYSA-N 2-[2-[[5-chloro-2-[2-methoxy-4-(4-methoxypiperidin-1-yl)anilino]pyrimidin-4-yl]amino]phenyl]prop-2-enamide Chemical compound C1CC(OC)CCN1C(C=C1OC)=CC=C1NC1=NC=C(Cl)C(NC=2C(=CC=CC=2)C(=C)C(N)=O)=N1 ZYWWKSPNANEDRB-UHFFFAOYSA-N 0.000 claims description 2
• JLWCHILGPBXURH-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-enoylazetidin-3-yl)acetamide Chemical compound COC1=CC(N2CCN(C)CC2)=CC=C1NC(N=1)=NC=C(Cl)C=1NC1=CC=CC=C1C(=O)C(=O)NC1CN(C(=O)C=C)C1 JLWCHILGPBXURH-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
• NGVDIADNZJLPMD-UHFFFAOYSA-N 2-[2-[[5-chloro-2-[2-methoxy-4-(4-methylpiperazin-1-yl)anilino]pyrimidin-4-yl]amino]phenyl]-2-oxoacetamide Chemical compound COC1=CC(N2CCN(C)CC2)=CC=C1NC(N=1)=NC=C(Cl)C=1NC1=CC=CC=C1C(=O)C(N)=O NGVDIADNZJLPMD-UHFFFAOYSA-N 0.000 claims description 2
• HUSAFYCXYIUNPB-UHFFFAOYSA-N 2-[2-[[5-chloro-2-[2-methoxy-4-(4-methylpiperazin-1-yl)anilino]pyrimidin-4-yl]amino]phenyl]-n,n-dimethyl-2-oxoacetamide Chemical compound COC1=CC(N2CCN(C)CC2)=CC=C1NC(N=1)=NC=C(Cl)C=1NC1=CC=CC=C1C(=O)C(=O)N(C)C HUSAFYCXYIUNPB-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
• WMJNZVCMRZGYMH-UHFFFAOYSA-N 2-[2-[[5-chloro-2-[2-methoxy-4-(4-methylpiperazin-1-yl)anilino]pyrimidin-4-yl]amino]phenyl]-n-methyl-2-oxoacetamide Chemical compound CNC(=O)C(=O)C1=CC=CC=C1NC1=NC(NC=2C(=CC(=CC=2)N2CCN(C)CC2)OC)=NC=C1Cl WMJNZVCMRZGYMH-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
• XNFZIAAEOHTBMQ-UHFFFAOYSA-N 2-[2-[[5-chloro-2-[2-methoxy-4-(4-prop-2-enoylpiperazin-1-yl)anilino]pyrimidin-4-yl]amino]phenyl]-n,n-dimethyl-2-oxoacetamide Chemical compound COC1=CC(N2CCN(CC2)C(=O)C=C)=CC=C1NC(N=1)=NC=C(Cl)C=1NC1=CC=CC=C1C(=O)C(=O)N(C)C XNFZIAAEOHTBMQ-UHFFFAOYSA-N 0.000 claims description 2
• IQISRWVHSPSIIQ-UHFFFAOYSA-N 2-[2-[[5-chloro-2-[2-methoxy-4-(4-propanoylpiperazin-1-yl)anilino]pyrimidin-4-yl]amino]phenyl]-n,n-dimethyl-2-oxoacetamide Chemical compound C1CN(C(=O)CC)CCN1C(C=C1OC)=CC=C1NC1=NC=C(Cl)C(NC=2C(=CC=CC=2)C(=O)C(=O)N(C)C)=N1 IQISRWVHSPSIIQ-UHFFFAOYSA-N 0.000 claims description 2
• ACUPPRKZIQHZNP-UHFFFAOYSA-N 2-[2-[[5-chloro-2-[2-methoxy-4-(4-propanoylpiperazin-1-yl)anilino]pyrimidin-4-yl]amino]phenyl]-n-methyl-2-oxoacetamide Chemical compound C1CN(C(=O)CC)CCN1C(C=C1OC)=CC=C1NC1=NC=C(Cl)C(NC=2C(=CC=CC=2)C(=O)C(=O)NC)=N1 ACUPPRKZIQHZNP-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
• LCWFBNTYQSRCSA-UHFFFAOYSA-N 2-[2-[[5-chloro-2-[3-methoxy-4-(1-methylpiperidin-4-yl)anilino]pyrimidin-4-yl]amino]phenyl]-N,N-dimethyl-2-oxoacetamide Chemical compound COc1cc(Nc2ncc(Cl)c(Nc3ccccc3C(=O)C(=O)N(C)C)n2)ccc1C1CCN(C)CC1 LCWFBNTYQSRCSA-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
• UBPDOQYPGGLAJG-UHFFFAOYSA-N 2-[2-[[5-chloro-2-[3-methoxy-4-(4-methylpiperazin-1-yl)anilino]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(N3CCN(C)CC3)=CC=2)=NC=C1Cl UBPDOQYPGGLAJG-UHFFFAOYSA-N 0.000 claims description 2
• GUKXDBLCVTYCCQ-UHFFFAOYSA-N 2-[2-[[5-chloro-2-[4-[4-(dimethylamino)piperidin-1-yl]-2-methoxyanilino]pyrimidin-4-yl]amino]phenyl]-2-oxo-n-piperidin-4-ylacetamide Chemical compound COC1=CC(N2CCC(CC2)N(C)C)=CC=C1NC(N=1)=NC=C(Cl)C=1NC1=CC=CC=C1C(=O)C(=O)NC1CCNCC1 GUKXDBLCVTYCCQ-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
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• 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
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• 125000001627 3 membered heterocyclic group Chemical group 0.000 claims description 2
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• 125000002373 5 membered heterocyclic group Chemical group 0.000 claims description 2
• 125000004070 6 membered heterocyclic group Chemical group 0.000 claims description 2
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• MZFLYNFLSFBMGV-UHFFFAOYSA-N ClC=1C(=NC(=NC=1)NC1=CC(=C(C=C1)C1CCN(CC1)C(C)C)OC)NC1=C(C=CC=C1)C(C(=O)N(C)C)=O Chemical compound ClC=1C(=NC(=NC=1)NC1=CC(=C(C=C1)C1CCN(CC1)C(C)C)OC)NC1=C(C=CC=C1)C(C(=O)N(C)C)=O MZFLYNFLSFBMGV-UHFFFAOYSA-N 0.000 claims description 2
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• DUKRJKCPYLPIHS-UHFFFAOYSA-N ClC=1C(=NC(=NC=1)NC=1C=CC(=C(C=1)NC(C(=C)CN1CCCCC1)=O)N1CCOCC1)NC1=C(C=CC=C1)C(C(=O)N(C)C)=O Chemical compound ClC=1C(=NC(=NC=1)NC=1C=CC(=C(C=1)NC(C(=C)CN1CCCCC1)=O)N1CCOCC1)NC1=C(C=CC=C1)C(C(=O)N(C)C)=O DUKRJKCPYLPIHS-UHFFFAOYSA-N 0.000 claims description 2
• LPGXRLSRVXWDEY-UHFFFAOYSA-N ClC=1C(=NC(=NC=1)NC=1C=CC(=C(C=1)NC(C=C)=O)N1CCOCC1)NC1=C(C=CC=C1)C(C(=O)N(C)C)=O Chemical compound ClC=1C(=NC(=NC=1)NC=1C=CC(=C(C=1)NC(C=C)=O)N1CCOCC1)NC1=C(C=CC=C1)C(C(=O)N(C)C)=O LPGXRLSRVXWDEY-UHFFFAOYSA-N 0.000 claims description 2
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• CDHPTZZAPQRQAT-UHFFFAOYSA-N ClC=1C(=NC(=NC=1)NC=1C=CC(=C(C=1)NC(CCN1CCOCC1)=O)F)NC1=C(C=CC=C1)C(C(=O)N(C)C)=O Chemical compound ClC=1C(=NC(=NC=1)NC=1C=CC(=C(C=1)NC(CCN1CCOCC1)=O)F)NC1=C(C=CC=C1)C(C(=O)N(C)C)=O CDHPTZZAPQRQAT-UHFFFAOYSA-N 0.000 claims description 2
• GSOMKMCGWICHRE-UHFFFAOYSA-N N-[3-[[5-chloro-4-[2-[2-(dimethylamino)-2-oxoacetyl]anilino]pyrimidin-2-yl]amino]-4-(oxolan-3-yloxy)phenyl]prop-2-enamide Chemical compound CN(C)C(=O)C(=O)c1ccccc1Nc1nc(Nc2cc(NC(=O)C=C)ccc2OC2CCOC2)ncc1Cl GSOMKMCGWICHRE-UHFFFAOYSA-N 0.000 claims description 2
• DSUNARYCAHZWRM-UHFFFAOYSA-N N-[3-[[5-chloro-4-[2-[2-(dimethylamino)-2-oxoacetyl]anilino]pyrimidin-2-yl]amino]-5-(trifluoromethyl)phenyl]prop-2-enamide Chemical compound CN(C)C(=O)C(=O)c1ccccc1Nc1nc(Nc2cc(NC(=O)C=C)cc(c2)C(F)(F)F)ncc1Cl DSUNARYCAHZWRM-UHFFFAOYSA-N 0.000 claims description 2
• XYNNIPLGJWWVEF-UHFFFAOYSA-N N-[5-[[5-chloro-4-[2-[2-(dimethylamino)-2-oxoacetyl]anilino]pyrimidin-2-yl]amino]-2-(1-methylazetidin-3-yl)oxyphenyl]prop-2-enamide Chemical compound ClC=1C(=NC(=NC1)NC=1C=CC(=C(C1)NC(C=C)=O)OC1CN(C1)C)NC1=C(C=CC=C1)C(C(=O)N(C)C)=O XYNNIPLGJWWVEF-UHFFFAOYSA-N 0.000 claims description 2
• DCURRGFFXYVFDO-UHFFFAOYSA-N N-[5-[[5-chloro-4-[2-[2-(dimethylamino)-2-oxoacetyl]anilino]pyrimidin-2-yl]amino]-2-[(dimethylamino)methyl]phenyl]prop-2-enamide Chemical compound CN(C)Cc1ccc(Nc2ncc(Cl)c(Nc3ccccc3C(=O)C(=O)N(C)C)n2)cc1NC(=O)C=C DCURRGFFXYVFDO-UHFFFAOYSA-N 0.000 claims description 2
• ULBWXUAQOGKPQB-UHFFFAOYSA-N N-[5-[[5-chloro-4-[2-[2-(dimethylamino)-2-oxoacetyl]anilino]pyrimidin-2-yl]amino]-2-[2-(dimethylamino)ethoxymethyl]phenyl]prop-2-enamide Chemical compound CN(C)CCOCc1ccc(Nc2ncc(Cl)c(Nc3ccccc3C(=O)C(=O)N(C)C)n2)cc1NC(=O)C=C ULBWXUAQOGKPQB-UHFFFAOYSA-N 0.000 claims description 2
• QLCRPNOOSLGYJX-UHFFFAOYSA-N N-[5-[[5-chloro-4-[2-[2-(dimethylamino)-2-oxoacetyl]anilino]pyrimidin-2-yl]amino]-2-[2-(dimethylamino)ethyl-methylamino]phenyl]prop-2-enamide Chemical compound ClC=1C(=NC(=NC=1)NC=1C=CC(=C(C=1)NC(C=C)=O)N(C)CCN(C)C)NC1=C(C=CC=C1)C(C(=O)N(C)C)=O QLCRPNOOSLGYJX-UHFFFAOYSA-N 0.000 claims description 2
• LTJQFOVXGLAFSY-UHFFFAOYSA-N N1CC(C1)OC1=C(C=C(C=C1)NC1=NC=C(C(=N1)NC1=C(C=CC=C1)C(C(=O)N(C)C)=O)Cl)NC(C=C)=O Chemical compound N1CC(C1)OC1=C(C=C(C=C1)NC1=NC=C(C(=N1)NC1=C(C=CC=C1)C(C(=O)N(C)C)=O)Cl)NC(C=C)=O LTJQFOVXGLAFSY-UHFFFAOYSA-N 0.000 claims description 2
• YNPNZTXNASCQKK-UHFFFAOYSA-N Phenanthrene Natural products C1=CC=C2C3=CC=CC=C3C=CC2=C1 YNPNZTXNASCQKK-UHFFFAOYSA-N 0.000 claims description 2
• DGEZNRSVGBDHLK-UHFFFAOYSA-N [1,10]phenanthroline Chemical compound C1=CN=C2C3=NC=CC=C3C=CC2=C1 DGEZNRSVGBDHLK-UHFFFAOYSA-N 0.000 claims description 2
• 125000003710 aryl alkyl group Chemical group 0.000 claims description 2
• YMAKLKBXEXREET-UHFFFAOYSA-N ethyl 2-[2-[[5-chloro-2-[4-[4-(dimethylamino)piperidin-1-yl]-2-methoxyanilino]pyrimidin-4-yl]amino]phenyl]-2-oxoacetate Chemical compound CCOC(=O)C(=O)C1=CC=CC=C1NC1=NC(NC=2C(=CC(=CC=2)N2CCC(CC2)N(C)C)OC)=NC=C1Cl YMAKLKBXEXREET-UHFFFAOYSA-N 0.000 claims description 2
• XOBKPQQVWGGIIJ-UHFFFAOYSA-N ethyl 2-[2-[[5-chloro-2-[4-[4-(dimethylamino)piperidin-1-yl]-2-methoxyanilino]pyrimidin-4-yl]amino]phenyl]prop-2-enoate Chemical compound CCOC(=O)C(=C)C1=CC=CC=C1NC1=NC(NC=2C(=CC(=CC=2)N2CCC(CC2)N(C)C)OC)=NC=C1Cl XOBKPQQVWGGIIJ-UHFFFAOYSA-N 0.000 claims description 2
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 2
• DLAKQYWOJCLWQC-UHFFFAOYSA-N n-(azetidin-3-yl)-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(=O)NC1CNC1 DLAKQYWOJCLWQC-UHFFFAOYSA-N 0.000 claims description 2
• YEOXWZJHNLGDRP-UHFFFAOYSA-N n-[3-[[5-chloro-4-[2-(2-morpholin-4-yl-2-oxoacetyl)anilino]pyrimidin-2-yl]amino]-4-methoxyphenyl]prop-2-enamide Chemical compound COC1=CC=C(NC(=O)C=C)C=C1NC1=NC=C(Cl)C(NC=2C(=CC=CC=2)C(=O)C(=O)N2CCOCC2)=N1 YEOXWZJHNLGDRP-UHFFFAOYSA-N 0.000 claims description 2
• GZHUIDLHDWAWMB-UHFFFAOYSA-N n-[3-[[5-chloro-4-[2-[2-(4-methylpiperazin-1-yl)-2-oxoacetyl]anilino]pyrimidin-2-yl]amino]-4-methoxyphenyl]prop-2-enamide Chemical compound COC1=CC=C(NC(=O)C=C)C=C1NC1=NC=C(Cl)C(NC=2C(=CC=CC=2)C(=O)C(=O)N2CCN(C)CC2)=N1 GZHUIDLHDWAWMB-UHFFFAOYSA-N 0.000 claims description 2
• WPUHCLIWMAWHIW-UHFFFAOYSA-N n-[3-[[5-chloro-4-[2-[2-(4-methylpiperazin-1-yl)-2-oxoacetyl]anilino]pyrimidin-2-yl]amino]phenyl]prop-2-enamide Chemical compound C1CN(C)CCN1C(=O)C(=O)C1=CC=CC=C1NC1=NC(NC=2C=C(NC(=O)C=C)C=CC=2)=NC=C1Cl WPUHCLIWMAWHIW-UHFFFAOYSA-N 0.000 claims description 2
• BLXSVBQFQSWEMG-UHFFFAOYSA-N n-[3-[[5-chloro-4-[2-[2-(dimethylamino)-2-oxoacetyl]anilino]pyrimidin-2-yl]amino]-4-methoxyphenyl]-2-(piperidin-1-ylmethyl)prop-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)CN1CCCCC1 BLXSVBQFQSWEMG-UHFFFAOYSA-N 0.000 claims description 2
• JEXXFCCMAHOJFM-UHFFFAOYSA-N n-[3-[[5-chloro-4-[2-[2-(dimethylamino)-2-oxoacetyl]anilino]pyrimidin-2-yl]amino]-4-methoxyphenyl]-2-(pyrrolidin-1-ylmethyl)prop-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)CN1CCCC1 JEXXFCCMAHOJFM-UHFFFAOYSA-N 0.000 claims description 2
• PVLSVSXTXJIWQT-UHFFFAOYSA-N n-[3-[[5-chloro-4-[2-[2-(dimethylamino)-2-oxoacetyl]anilino]pyrimidin-2-yl]amino]-4-methoxyphenyl]-2-[(dimethylamino)methyl]prop-2-enamide Chemical compound COC1=CC=C(NC(=O)C(=C)CN(C)C)C=C1NC1=NC=C(Cl)C(NC=2C(=CC=CC=2)C(=O)C(=O)N(C)C)=N1 PVLSVSXTXJIWQT-UHFFFAOYSA-N 0.000 claims description 2
• BHTWOBOPKRZPIA-UHFFFAOYSA-N n-[3-[[5-chloro-4-[2-[2-(dimethylamino)-2-oxoacetyl]anilino]pyrimidin-2-yl]amino]-4-methoxyphenyl]-3-methylbut-2-enamide Chemical compound COC1=CC=C(NC(=O)C=C(C)C)C=C1NC1=NC=C(Cl)C(NC=2C(=CC=CC=2)C(=O)C(=O)N(C)C)=N1 BHTWOBOPKRZPIA-UHFFFAOYSA-N 0.000 claims description 2
• OKCOQQXHDZUFTL-UHFFFAOYSA-N n-[3-[[5-chloro-4-[2-[2-(dimethylamino)-2-oxoacetyl]anilino]pyrimidin-2-yl]amino]-4-methoxyphenyl]prop-2-enamide Chemical compound COC1=CC=C(NC(=O)C=C)C=C1NC1=NC=C(Cl)C(NC=2C(=CC=CC=2)C(=O)C(=O)N(C)C)=N1 OKCOQQXHDZUFTL-UHFFFAOYSA-N 0.000 claims description 2
• ZFWDXCCOEDXJEO-UHFFFAOYSA-N n-[3-[[5-chloro-4-[2-[2-[2-(dimethylamino)ethylamino]-2-oxoacetyl]anilino]pyrimidin-2-yl]amino]-4-methoxyphenyl]prop-2-enamide Chemical compound COC1=CC=C(NC(=O)C=C)C=C1NC1=NC=C(Cl)C(NC=2C(=CC=CC=2)C(=O)C(=O)NCCN(C)C)=N1 ZFWDXCCOEDXJEO-UHFFFAOYSA-N 0.000 claims description 2
• FGVHSXSFGJBPAC-UHFFFAOYSA-N n-[3-[[5-chloro-4-[2-[2-[2-(dimethylamino)ethylamino]-2-oxoacetyl]anilino]pyrimidin-2-yl]amino]phenyl]prop-2-enamide Chemical compound CN(C)CCNC(=O)C(=O)C1=CC=CC=C1NC1=NC(NC=2C=C(NC(=O)C=C)C=CC=2)=NC=C1Cl FGVHSXSFGJBPAC-UHFFFAOYSA-N 0.000 claims description 2
• BUYIBJZIHKSKDT-UHFFFAOYSA-N n-[5-[[4-[2-[2-(dimethylamino)-2-oxoacetyl]anilino]-5-methylpyrimidin-2-yl]amino]-2-methoxyphenyl]prop-2-enamide Chemical compound C1=C(NC(=O)C=C)C(OC)=CC=C1NC1=NC=C(C)C(NC=2C(=CC=CC=2)C(=O)C(=O)N(C)C)=N1 BUYIBJZIHKSKDT-UHFFFAOYSA-N 0.000 claims description 2
• LMGLKFHIVGJIEB-UHFFFAOYSA-N n-[5-[[5-chloro-4-[2-(2-morpholin-4-yl-2-oxoacetyl)anilino]pyrimidin-2-yl]amino]-2-methoxyphenyl]prop-2-enamide Chemical compound C1=C(NC(=O)C=C)C(OC)=CC=C1NC1=NC=C(Cl)C(NC=2C(=CC=CC=2)C(=O)C(=O)N2CCOCC2)=N1 LMGLKFHIVGJIEB-UHFFFAOYSA-N 0.000 claims description 2
• UOUZXAIBJBCTIX-UHFFFAOYSA-N n-[5-[[5-chloro-4-[2-[2-(4-methylpiperazin-1-yl)-2-oxoacetyl]anilino]pyrimidin-2-yl]amino]-2-methoxyphenyl]prop-2-enamide Chemical compound C1=C(NC(=O)C=C)C(OC)=CC=C1NC1=NC=C(Cl)C(NC=2C(=CC=CC=2)C(=O)C(=O)N2CCN(C)CC2)=N1 UOUZXAIBJBCTIX-UHFFFAOYSA-N 0.000 claims description 2
• BQGJJCRERBDMEC-UHFFFAOYSA-N n-[5-[[5-chloro-4-[2-[2-(dimethylamino)-2-oxoacetyl]anilino]pyrimidin-2-yl]amino]-2-[2-(dimethylamino)ethoxy]phenyl]-3-methoxypropanamide Chemical compound C1=C(OCCN(C)C)C(NC(=O)CCOC)=CC(NC=2N=C(NC=3C(=CC=CC=3)C(=O)C(=O)N(C)C)C(Cl)=CN=2)=C1 BQGJJCRERBDMEC-UHFFFAOYSA-N 0.000 claims description 2
• YLORQIIPEBGMJH-UHFFFAOYSA-N n-[5-[[5-chloro-4-[2-[2-(dimethylamino)-2-oxoacetyl]anilino]pyrimidin-2-yl]amino]-2-cyclopentyloxyphenyl]prop-2-enamide Chemical compound CN(C)C(=O)C(=O)C1=CC=CC=C1NC1=NC(NC=2C=C(NC(=O)C=C)C(OC3CCCC3)=CC=2)=NC=C1Cl YLORQIIPEBGMJH-UHFFFAOYSA-N 0.000 claims description 2
• ZWECPWDKNQOSQQ-UHFFFAOYSA-N n-[5-[[5-chloro-4-[2-[2-(dimethylamino)-2-oxoacetyl]anilino]pyrimidin-2-yl]amino]-2-cyclopropyloxyphenyl]prop-2-enamide Chemical compound CN(C)C(=O)C(=O)C1=CC=CC=C1NC1=NC(NC=2C=C(NC(=O)C=C)C(OC3CC3)=CC=2)=NC=C1Cl ZWECPWDKNQOSQQ-UHFFFAOYSA-N 0.000 claims description 2
• LUIUMZOKTAQVPT-UHFFFAOYSA-N n-[5-[[5-chloro-4-[2-[2-(dimethylamino)-2-oxoacetyl]anilino]pyrimidin-2-yl]amino]-2-fluoro-4-methoxyphenyl]prop-2-enamide Chemical compound COC1=CC(F)=C(NC(=O)C=C)C=C1NC1=NC=C(Cl)C(NC=2C(=CC=CC=2)C(=O)C(=O)N(C)C)=N1 LUIUMZOKTAQVPT-UHFFFAOYSA-N 0.000 claims description 2
• DDNLSAZMIXQCQD-UHFFFAOYSA-N n-[5-[[5-chloro-4-[2-[2-(dimethylamino)-2-oxoacetyl]anilino]pyrimidin-2-yl]amino]-2-methoxyphenyl]prop-2-enamide Chemical compound C1=C(NC(=O)C=C)C(OC)=CC=C1NC1=NC=C(Cl)C(NC=2C(=CC=CC=2)C(=O)C(=O)N(C)C)=N1 DDNLSAZMIXQCQD-UHFFFAOYSA-N 0.000 claims description 2
• UAIQANFZHONYNQ-UHFFFAOYSA-N n-[5-[[5-chloro-4-[2-[2-(dimethylamino)-2-oxoacetyl]anilino]pyrimidin-2-yl]amino]-4-fluoro-2-methoxyphenyl]prop-2-enamide Chemical compound C1=C(NC(=O)C=C)C(OC)=CC(F)=C1NC1=NC=C(Cl)C(NC=2C(=CC=CC=2)C(=O)C(=O)N(C)C)=N1 UAIQANFZHONYNQ-UHFFFAOYSA-N 0.000 claims description 2
• HMVFMTSRDAEQCX-UHFFFAOYSA-N n-[5-[[5-chloro-4-[2-[2-(dimethylamino)-2-oxoacetyl]anilino]pyrimidin-2-yl]amino]-4-methoxy-2-(2-morpholin-4-ylethoxy)phenyl]prop-2-enamide Chemical compound C=CC(=O)NC=1C=C(NC=2N=C(NC=3C(=CC=CC=3)C(=O)C(=O)N(C)C)C(Cl)=CN=2)C(OC)=CC=1OCCN1CCOCC1 HMVFMTSRDAEQCX-UHFFFAOYSA-N 0.000 claims description 2
• RHWLUCXWTWQGHA-UHFFFAOYSA-N n-[5-[[5-chloro-4-[2-[2-(dimethylamino)-2-oxoacetyl]anilino]pyrimidin-2-yl]amino]-4-methoxy-2-(3-morpholin-4-ylpropoxy)phenyl]prop-2-enamide Chemical compound C=CC(=O)NC=1C=C(NC=2N=C(NC=3C(=CC=CC=3)C(=O)C(=O)N(C)C)C(Cl)=CN=2)C(OC)=CC=1OCCCN1CCOCC1 RHWLUCXWTWQGHA-UHFFFAOYSA-N 0.000 claims description 2
• KZEIBELCNXRNPM-UHFFFAOYSA-N n-[5-[[5-chloro-4-[2-[2-(methylamino)-2-oxoacetyl]anilino]pyrimidin-2-yl]amino]-2-[2-(dimethylamino)ethoxy]-4-methoxyphenyl]prop-2-enamide Chemical compound CNC(=O)C(=O)C1=CC=CC=C1NC1=NC(NC=2C(=CC(OCCN(C)C)=C(NC(=O)C=C)C=2)OC)=NC=C1Cl KZEIBELCNXRNPM-UHFFFAOYSA-N 0.000 claims description 2
• VMSMCXTZJPUKBB-UHFFFAOYSA-N n-[5-[[5-chloro-4-[2-[2-(methylamino)-2-oxoacetyl]anilino]pyrimidin-2-yl]amino]-2-methoxyphenyl]prop-2-enamide Chemical compound CNC(=O)C(=O)C1=CC=CC=C1NC1=NC(NC=2C=C(NC(=O)C=C)C(OC)=CC=2)=NC=C1Cl VMSMCXTZJPUKBB-UHFFFAOYSA-N 0.000 claims description 2
• HKNYNUXSBRUGNV-UHFFFAOYSA-N n-[5-[[5-chloro-4-[2-[2-(methylamino)-2-oxoacetyl]anilino]pyrimidin-2-yl]amino]-4-methoxy-2-(4-methylpiperazin-1-yl)phenyl]prop-2-enamide Chemical compound CNC(=O)C(=O)C1=CC=CC=C1NC1=NC(NC=2C(=CC(=C(NC(=O)C=C)C=2)N2CCN(C)CC2)OC)=NC=C1Cl HKNYNUXSBRUGNV-UHFFFAOYSA-N 0.000 claims description 2
• UJROFNGOCICAHD-UHFFFAOYSA-N n-[5-[[5-chloro-4-[2-[2-[2-(dimethylamino)ethyl-methylamino]-2-oxoacetyl]anilino]pyrimidin-2-yl]amino]-2-methoxyphenyl]prop-2-enamide Chemical compound C1=C(NC(=O)C=C)C(OC)=CC=C1NC1=NC=C(Cl)C(NC=2C(=CC=CC=2)C(=O)C(=O)N(C)CCN(C)C)=N1 UJROFNGOCICAHD-UHFFFAOYSA-N 0.000 claims description 2
• DPYULPSMGNLETO-UHFFFAOYSA-N n-[5-[[5-chloro-4-[2-[2-[2-(dimethylamino)ethylamino]-2-oxoacetyl]anilino]pyrimidin-2-yl]amino]-2-methoxyphenyl]prop-2-enamide Chemical compound C1=C(NC(=O)C=C)C(OC)=CC=C1NC1=NC=C(Cl)C(NC=2C(=CC=CC=2)C(=O)C(=O)NCCN(C)C)=N1 DPYULPSMGNLETO-UHFFFAOYSA-N 0.000 claims description 2
• 125000004433 nitrogen atom Chemical group N* 0.000 claims description 2
• 229910052698 phosphorus Inorganic materials 0.000 claims description 2
• 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 claims description 2
• 229920002554 vinyl polymer Chemical group 0.000 claims description 2
• 102000052116 epidermal growth factor receptor activity proteins Human genes 0.000 claims 13
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• YOHYSYJDKVYCJI-UHFFFAOYSA-N n-[3-[[6-[3-(trifluoromethyl)anilino]pyrimidin-4-yl]amino]phenyl]cyclopropanecarboxamide Chemical compound FC(F)(F)C1=CC=CC(NC=2N=CN=C(NC=3C=C(NC(=O)C4CC4)C=CC=3)C=2)=C1 YOHYSYJDKVYCJI-UHFFFAOYSA-N 0.000 claims 13
• 229940117913 acrylamide Drugs 0.000 claims 6
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• DADKXUOVSZYHMW-MDWZMJQESA-N (E)-N-[3-[[5-chloro-4-[2-[2-(dimethylamino)-2-oxoacetyl]anilino]pyrimidin-2-yl]amino]phenyl]-4-(dimethylamino)but-2-enamide Chemical compound ClC=1C(=NC(=NC=1)NC=1C=C(C=CC=1)NC(\C=C\CN(C)C)=O)NC1=C(C=CC=C1)C(C(=O)N(C)C)=O DADKXUOVSZYHMW-MDWZMJQESA-N 0.000 claims 1
• MRBIBUMZUMFILI-DHZHZOJOSA-N (e)-n-[3-[[5-chloro-4-[2-[2-(dimethylamino)-2-oxoacetyl]anilino]pyrimidin-2-yl]amino]-4-methoxyphenyl]-4-(dimethylamino)but-2-enamide Chemical compound COC1=CC=C(NC(=O)\C=C\CN(C)C)C=C1NC1=NC=C(Cl)C(NC=2C(=CC=CC=2)C(=O)C(=O)N(C)C)=N1 MRBIBUMZUMFILI-DHZHZOJOSA-N 0.000 claims 1
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• ODYWZOHJRMOVNL-FMIVXFBMSA-N (e)-n-[3-[[5-chloro-4-[2-[2-(dimethylamino)-2-oxoacetyl]anilino]pyrimidin-2-yl]amino]-4-methoxyphenyl]-4-piperidin-1-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\CN1CCCCC1 ODYWZOHJRMOVNL-FMIVXFBMSA-N 0.000 claims 1
• 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 1
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• MHBWCASJSCTIPX-UHFFFAOYSA-N 1-[2-[[5-chloro-2-[4-[4-(dimethylamino)piperidin-1-yl]-2-methoxyanilino]pyrimidin-4-yl]amino]phenyl]-3-(dimethylamino)propane-1,2-dione Chemical compound COC1=CC(N2CCC(CC2)N(C)C)=CC=C1NC(N=1)=NC=C(Cl)C=1NC1=CC=CC=C1C(=O)C(=O)CN(C)C MHBWCASJSCTIPX-UHFFFAOYSA-N 0.000 claims 1
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• CEVCZHWHGPPYAQ-UHFFFAOYSA-N 2-[2-[[2-(5-methyl-4-piperidin-4-yl-2-propan-2-yloxyanilino)-5-(trifluoromethyl)pyrimidin-4-yl]amino]phenyl]-2-oxoacetamide Chemical compound CC=1C=C(NC=2N=C(NC=3C(=CC=CC=3)C(=O)C(N)=O)C(=CN=2)C(F)(F)F)C(OC(C)C)=CC=1C1CCNCC1 CEVCZHWHGPPYAQ-UHFFFAOYSA-N 0.000 claims 1
• CDIFEYRGCVEXIK-UHFFFAOYSA-N 2-[2-[[2-[4-(1-acetylpiperidin-4-yl)-3-methoxyanilino]-5-chloropyrimidin-4-yl]amino]phenyl]-N,N-dimethyl-2-oxoacetamide Chemical compound C(C)(=O)N1CCC(CC1)C1=C(C=C(C=C1)NC1=NC=C(C(=N1)NC1=C(C=CC=C1)C(C(=O)N(C)C)=O)Cl)OC CDIFEYRGCVEXIK-UHFFFAOYSA-N 0.000 claims 1
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• NUMIRKOBHLNKEQ-UHFFFAOYSA-N 2-[2-[[5-chloro-2-(4-fluoro-3-methoxyanilino)pyrimidin-4-yl]amino]phenyl]-2-oxo-n-(1-prop-2-enoylpiperidin-4-yl)acetamide Chemical compound C1=C(F)C(OC)=CC(NC=2N=C(NC=3C(=CC=CC=3)C(=O)C(=O)NC3CCN(CC3)C(=O)C=C)C(Cl)=CN=2)=C1 NUMIRKOBHLNKEQ-UHFFFAOYSA-N 0.000 claims 1
• 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 1
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