CA2882158A1 - Vegfr3 inhibitors - Google Patents

Info

Publication number

CA2882158A1

CA2882158A1 CA2882158A CA2882158A CA2882158A1 CA 2882158 A1 CA2882158 A1 CA 2882158A1 CA 2882158 A CA2882158 A CA 2882158A CA 2882158 A CA2882158 A CA 2882158A CA 2882158 A1 CA2882158 A1 CA 2882158A1

Authority

CA

Canada

Prior art keywords

phenyl

ethyl

pyrimidin

amino

cyclopropanecarboxamide

Prior art date

2012-08-17

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.)

Abandoned

Links

• Espacenet
• Global Dossier
• CIPO
• Discuss

• 229940127432 VEGFR3 Inhibitors Drugs 0.000 title description 2
• 150000001875 compounds Chemical class 0.000 claims abstract description 368
• 238000000034 method Methods 0.000 claims abstract description 57
• 206010028980 Neoplasm Diseases 0.000 claims abstract description 50
• 201000011510 cancer Diseases 0.000 claims abstract description 39
• 238000011282 treatment Methods 0.000 claims abstract description 30
• 230000005764 inhibitory process Effects 0.000 claims abstract description 15
• 201000010099 disease Diseases 0.000 claims abstract description 13
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 13
• 238000002360 preparation method Methods 0.000 claims abstract description 11
• 230000001668 ameliorated effect Effects 0.000 claims abstract description 8
• 239000008177 pharmaceutical agent Substances 0.000 claims abstract description 8
• 230000008569 process Effects 0.000 claims abstract description 8
• 239000000203 mixture Substances 0.000 claims description 203
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 160
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 137
• 125000000217 alkyl group Chemical group 0.000 claims description 104
• -1 cyclopropylidene, cyclobutylidene, cyclopentylidene Chemical group 0.000 claims description 103
• 125000001424 substituent group Chemical group 0.000 claims description 97
• AIMMVWOEOZMVMS-UHFFFAOYSA-N cyclopropanecarboxamide Chemical compound NC(=O)C1CC1 AIMMVWOEOZMVMS-UHFFFAOYSA-N 0.000 claims description 76
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 72
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 68
• 150000003839 salts Chemical class 0.000 claims description 60
• 229940002612 prodrug Drugs 0.000 claims description 57
• 239000000651 prodrug Substances 0.000 claims description 57
• 239000012453 solvate Substances 0.000 claims description 55
• 102100033179 Vascular endothelial growth factor receptor 3 Human genes 0.000 claims description 53
• 125000006645 (C3-C4) cycloalkyl group Chemical group 0.000 claims description 37
• 229910052739 hydrogen Inorganic materials 0.000 claims description 35
• 239000003795 chemical substances by application Substances 0.000 claims description 25
• 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 23
• 229910052731 fluorine Inorganic materials 0.000 claims description 20
• 125000005842 heteroatom Chemical group 0.000 claims description 20
• 125000005843 halogen group Chemical group 0.000 claims description 18
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 18
• 125000004076 pyridyl group Chemical group 0.000 claims description 17
• 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 16
• 229910052799 carbon Inorganic materials 0.000 claims description 16
• 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 claims description 14
• 125000004527 pyrimidin-4-yl group Chemical group N1=CN=C(C=C1)* 0.000 claims description 14
• 125000006164 6-membered heteroaryl group Chemical group 0.000 claims description 13
• 125000003226 pyrazolyl group Chemical group 0.000 claims description 13
• YNPZQOCKZKZHEM-UHFFFAOYSA-N 1-[2-[2-[5-chloro-2-[(6-piperidin-4-ylpyridin-3-yl)amino]pyrimidin-4-yl]ethyl]phenyl]cyclopropane-1-carboxamide Chemical compound C=1C=CC=C(CCC=2C(=CN=C(NC=3C=NC(=CC=3)C3CCNCC3)N=2)Cl)C=1C1(C(=O)N)CC1 YNPZQOCKZKZHEM-UHFFFAOYSA-N 0.000 claims description 12
• 125000001072 heteroaryl group Chemical group 0.000 claims description 12
• RTGQEFNYCLEWPU-UHFFFAOYSA-N 1-[2-[2-[2-[(6-piperidin-4-ylpyridin-3-yl)amino]-5-(trifluoromethyl)pyrimidin-4-yl]ethyl]phenyl]cyclopropane-1-carboxamide Chemical compound C=1C=CC=C(CCC=2C(=CN=C(NC=3C=NC(=CC=3)C3CCNCC3)N=2)C(F)(F)F)C=1C1(C(=O)N)CC1 RTGQEFNYCLEWPU-UHFFFAOYSA-N 0.000 claims description 11
• IALBGKOBFXRYIF-UHFFFAOYSA-N 1-[2-[2-[5-chloro-2-(pyridin-3-ylamino)pyrimidin-4-yl]ethyl]phenyl]cyclopropane-1-carboxamide Chemical compound C=1C=CC=C(CCC=2C(=CN=C(NC=3C=NC=CC=3)N=2)Cl)C=1C1(C(=O)N)CC1 IALBGKOBFXRYIF-UHFFFAOYSA-N 0.000 claims description 10
• 125000006163 5-membered heteroaryl group Chemical group 0.000 claims description 10
• 239000003814 drug Substances 0.000 claims description 10
• 125000000623 heterocyclic group Chemical group 0.000 claims description 10
• YCIIZJUIBNPNED-UHFFFAOYSA-N 1-[2-[2-[2-(4-piperidin-4-ylanilino)-5-(trifluoromethyl)pyrimidin-4-yl]ethyl]phenyl]cyclopropane-1-carboxamide Chemical compound C=1C=CC=C(CCC=2C(=CN=C(NC=3C=CC(=CC=3)C3CCNCC3)N=2)C(F)(F)F)C=1C1(C(=O)N)CC1 YCIIZJUIBNPNED-UHFFFAOYSA-N 0.000 claims description 9
• SFMZLILRNZSYMD-UHFFFAOYSA-N 1-[2-[2-[5-chloro-2-(1,3-oxazol-2-ylamino)pyrimidin-4-yl]ethyl]phenyl]cyclopropane-1-carboxamide Chemical compound C=1C=CC=C(CCC=2C(=CN=C(NC=3OC=CN=3)N=2)Cl)C=1C1(C(=O)N)CC1 SFMZLILRNZSYMD-UHFFFAOYSA-N 0.000 claims description 9
• MHBVMQSXQLYCRO-UHFFFAOYSA-N 1-[2-[2-[2-[(6-acetylpyridin-3-yl)amino]-5-chloropyrimidin-4-yl]ethyl]phenyl]cyclopropane-1-carboxamide Chemical compound C1=NC(C(=O)C)=CC=C1NC1=NC=C(Cl)C(CCC=2C(=CC=CC=2)C2(CC2)C(N)=O)=N1 MHBVMQSXQLYCRO-UHFFFAOYSA-N 0.000 claims description 8
• IDBAAYPNWLPEBC-UHFFFAOYSA-N 1-[2-[2-[5-chloro-2-(1h-pyrazol-4-ylamino)pyrimidin-4-yl]ethyl]phenyl]cyclopropane-1-carboxamide Chemical compound C=1C=CC=C(CCC=2C(=CN=C(NC3=CNN=C3)N=2)Cl)C=1C1(C(=O)N)CC1 IDBAAYPNWLPEBC-UHFFFAOYSA-N 0.000 claims description 8
• OZGDLMQYSZELNV-UHFFFAOYSA-N 1-[2-[2-[5-chloro-2-(pyrimidin-5-ylamino)pyrimidin-4-yl]ethyl]phenyl]cyclopropane-1-carboxamide Chemical compound C=1C=CC=C(CCC=2C(=CN=C(NC=3C=NC=NC=3)N=2)Cl)C=1C1(C(=O)N)CC1 OZGDLMQYSZELNV-UHFFFAOYSA-N 0.000 claims description 8
• KUZRTSMZHWGUIV-UHFFFAOYSA-N 1-[2-[2-[5-chloro-2-[(1-methylpyrazol-4-yl)amino]pyrimidin-4-yl]ethyl]phenyl]cyclopropane-1-carboxamide Chemical compound C1=NN(C)C=C1NC1=NC=C(Cl)C(CCC=2C(=CC=CC=2)C2(CC2)C(N)=O)=N1 KUZRTSMZHWGUIV-UHFFFAOYSA-N 0.000 claims description 8
• USEUEHCDMYWPSG-UHFFFAOYSA-N 1-[2-[2-[5-chloro-2-[[5-(1-methylpiperidin-3-yl)pyridin-3-yl]amino]pyrimidin-4-yl]ethyl]phenyl]cyclopropane-1-carboxamide Chemical compound C1N(C)CCCC1C1=CN=CC(NC=2N=C(CCC=3C(=CC=CC=3)C3(CC3)C(N)=O)C(Cl)=CN=2)=C1 USEUEHCDMYWPSG-UHFFFAOYSA-N 0.000 claims description 8
• JKWCRJGFBDYBDW-UHFFFAOYSA-N 2-[2-[2-[5-chloro-2-[(6-piperidin-4-ylpyridin-3-yl)amino]pyrimidin-4-yl]ethyl]phenyl]propanamide Chemical compound NC(=O)C(C)C1=CC=CC=C1CCC1=NC(NC=2C=NC(=CC=2)C2CCNCC2)=NC=C1Cl JKWCRJGFBDYBDW-UHFFFAOYSA-N 0.000 claims description 8
• 230000002401 inhibitory effect Effects 0.000 claims description 8
• 238000002560 therapeutic procedure Methods 0.000 claims description 8
• QXWHXZVEZDYDHA-UHFFFAOYSA-N 1-[2-[2-[2-[4-(azetidin-3-yl)anilino]-5-(trifluoromethyl)pyrimidin-4-yl]ethyl]phenyl]cyclopropane-1-carboxamide Chemical compound C=1C=CC=C(CCC=2C(=CN=C(NC=3C=CC(=CC=3)C3CNC3)N=2)C(F)(F)F)C=1C1(C(=O)N)CC1 QXWHXZVEZDYDHA-UHFFFAOYSA-N 0.000 claims description 7
• INJXBWVPVJXXSO-UHFFFAOYSA-N 2-[2-[2-[5-chloro-2-(pyrimidin-5-ylamino)pyrimidin-4-yl]ethyl]phenyl]propanamide Chemical compound NC(=O)C(C)C1=CC=CC=C1CCC1=NC(NC=2C=NC=NC=2)=NC=C1Cl INJXBWVPVJXXSO-UHFFFAOYSA-N 0.000 claims description 7
• 241001465754 Metazoa Species 0.000 claims description 7
• 238000001727 in vivo Methods 0.000 claims description 7
• XUPSPUNWHXFDCO-UHFFFAOYSA-N 1-[2-[2-(2-anilino-5-chloropyrimidin-4-yl)ethyl]phenyl]cyclopropane-1-carboxamide Chemical compound C=1C=CC=C(CCC=2C(=CN=C(NC=3C=CC=CC=3)N=2)Cl)C=1C1(C(=O)N)CC1 XUPSPUNWHXFDCO-UHFFFAOYSA-N 0.000 claims description 6
• RLIHQICAODIXMW-UHFFFAOYSA-N 1-[2-[2-[2-[4-(1-methylpiperidin-4-yl)anilino]-5-(trifluoromethyl)pyrimidin-4-yl]ethyl]phenyl]cyclopropane-1-carboxamide Chemical compound C1CN(C)CCC1C(C=C1)=CC=C1NC1=NC=C(C(F)(F)F)C(CCC=2C(=CC=CC=2)C2(CC2)C(N)=O)=N1 RLIHQICAODIXMW-UHFFFAOYSA-N 0.000 claims description 6
• ADECUQYWGSIQCQ-UHFFFAOYSA-N 1-[2-[2-[2-[[6-(1-aminoethyl)pyridin-3-yl]amino]-5-chloropyrimidin-4-yl]ethyl]phenyl]cyclopropane-1-carboxamide Chemical compound C1=NC(C(N)C)=CC=C1NC1=NC=C(Cl)C(CCC=2C(=CC=CC=2)C2(CC2)C(N)=O)=N1 ADECUQYWGSIQCQ-UHFFFAOYSA-N 0.000 claims description 6
• PPFXUUIFCFAGQI-UHFFFAOYSA-N 1-[2-[2-[5-chloro-2-(pyridazin-4-ylamino)pyrimidin-4-yl]ethyl]phenyl]cyclopropane-1-carboxamide Chemical compound C=1C=CC=C(CCC=2C(=CN=C(NC=3C=NN=CC=3)N=2)Cl)C=1C1(C(=O)N)CC1 PPFXUUIFCFAGQI-UHFFFAOYSA-N 0.000 claims description 6
• VWIGHYQLPWBDMA-UHFFFAOYSA-N 1-[2-[2-[5-chloro-2-[(6-cyanopyridin-3-yl)amino]pyrimidin-4-yl]ethyl]phenyl]cyclopropane-1-carboxamide Chemical compound C=1C=CC=C(CCC=2C(=CN=C(NC=3C=NC(=CC=3)C#N)N=2)Cl)C=1C1(C(=O)N)CC1 VWIGHYQLPWBDMA-UHFFFAOYSA-N 0.000 claims description 6
• VDXARSHJPFZWJT-UHFFFAOYSA-N 1-[2-[2-[5-chloro-2-[4-(1-methylpiperidin-4-yl)anilino]pyrimidin-4-yl]ethyl]phenyl]cyclopropane-1-carboxamide Chemical compound C1CN(C)CCC1C(C=C1)=CC=C1NC1=NC=C(Cl)C(CCC=2C(=CC=CC=2)C2(CC2)C(N)=O)=N1 VDXARSHJPFZWJT-UHFFFAOYSA-N 0.000 claims description 6
• JGVFAQMWQRTRLJ-UHFFFAOYSA-N 2-[2-[2-[5-chloro-2-(pyridazin-4-ylamino)pyrimidin-4-yl]ethyl]phenyl]propanamide Chemical compound NC(=O)C(C)C1=CC=CC=C1CCC1=NC(NC=2C=NN=CC=2)=NC=C1Cl JGVFAQMWQRTRLJ-UHFFFAOYSA-N 0.000 claims description 6
• VYDHVXKWBJAYCG-UHFFFAOYSA-N 2-[2-[2-[5-chloro-2-(pyridin-3-ylamino)pyrimidin-4-yl]ethyl]phenyl]propanamide Chemical compound NC(=O)C(C)C1=CC=CC=C1CCC1=NC(NC=2C=NC=CC=2)=NC=C1Cl VYDHVXKWBJAYCG-UHFFFAOYSA-N 0.000 claims description 6
• JAHMDTQVHMQVJF-UHFFFAOYSA-N 2-[2-[2-[5-chloro-2-[(1-methylpyrazol-4-yl)amino]pyrimidin-4-yl]ethyl]phenyl]propanamide Chemical compound NC(=O)C(C)C1=CC=CC=C1CCC1=NC(NC2=CN(C)N=C2)=NC=C1Cl JAHMDTQVHMQVJF-UHFFFAOYSA-N 0.000 claims description 6
• OCHGDSBDDOYVSU-UHFFFAOYSA-N 2-[2-[2-[5-chloro-2-[(6-methylpyridin-3-yl)amino]pyrimidin-4-yl]ethyl]phenyl]propanamide Chemical compound NC(=O)C(C)C1=CC=CC=C1CCC1=NC(NC=2C=NC(C)=CC=2)=NC=C1Cl OCHGDSBDDOYVSU-UHFFFAOYSA-N 0.000 claims description 6
• LTCMPYHWTMXQPF-UHFFFAOYSA-N 2-[2-[2-[5-chloro-2-[[6-(1-methylpiperidin-4-yl)pyridin-3-yl]amino]pyrimidin-4-yl]ethyl]phenyl]propanamide Chemical compound NC(=O)C(C)C1=CC=CC=C1CCC1=NC(NC=2C=NC(=CC=2)C2CCN(C)CC2)=NC=C1Cl LTCMPYHWTMXQPF-UHFFFAOYSA-N 0.000 claims description 6
• 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 claims description 6
• 239000003085 diluting agent Substances 0.000 claims description 6
• MZYDUEWRHJEHIO-UHFFFAOYSA-N 1-[2-[2-[5-chloro-2-[[6-(trifluoromethyl)pyridin-3-yl]amino]pyrimidin-4-yl]ethyl]phenyl]cyclopropane-1-carboxamide Chemical compound C=1C=CC=C(CCC=2C(=CN=C(NC=3C=NC(=CC=3)C(F)(F)F)N=2)Cl)C=1C1(C(=O)N)CC1 MZYDUEWRHJEHIO-UHFFFAOYSA-N 0.000 claims description 5
• RKVTUBMTXZINFU-UHFFFAOYSA-N 2-[2-[2-[5-chloro-2-(1h-pyrazol-4-ylamino)pyrimidin-4-yl]ethyl]phenyl]propanamide Chemical compound NC(=O)C(C)C1=CC=CC=C1CCC1=NC(NC2=CNN=C2)=NC=C1Cl RKVTUBMTXZINFU-UHFFFAOYSA-N 0.000 claims description 5
• 230000000259 anti-tumor effect Effects 0.000 claims description 5
• 125000001313 C5-C10 heteroaryl group Chemical group 0.000 claims description 4
• 238000011394 anticancer treatment Methods 0.000 claims description 4
• 239000003937 drug carrier Substances 0.000 claims description 4
• 208000014829 head and neck neoplasm Diseases 0.000 claims description 4
• 238000000338 in vitro Methods 0.000 claims description 4
• 206010006187 Breast cancer Diseases 0.000 claims description 3
• 208000026310 Breast neoplasm Diseases 0.000 claims description 3
• 201000001441 melanoma Diseases 0.000 claims description 3
• 201000010536 head and neck cancer Diseases 0.000 claims description 2
• 101000851030 Homo sapiens Vascular endothelial growth factor receptor 3 Proteins 0.000 claims 3
• UMEFYEWFNFNLHP-UHFFFAOYSA-N 1-[2-[2-[2-[(1-methylpyrazol-4-yl)amino]-5-(trifluoromethyl)pyrimidin-4-yl]ethyl]phenyl]cyclopropane-1-carboxamide Chemical compound C1=NN(C)C=C1NC1=NC=C(C(F)(F)F)C(CCC=2C(=CC=CC=2)C2(CC2)C(N)=O)=N1 UMEFYEWFNFNLHP-UHFFFAOYSA-N 0.000 claims 2
• REZLRWDJAZYYMQ-UHFFFAOYSA-N 1-[2-[2-[2-[(6-methoxypyridin-3-yl)amino]-5-(trifluoromethyl)pyrimidin-4-yl]ethyl]phenyl]cyclopropane-1-carboxamide Chemical compound C1=NC(OC)=CC=C1NC1=NC=C(C(F)(F)F)C(CCC=2C(=CC=CC=2)C2(CC2)C(N)=O)=N1 REZLRWDJAZYYMQ-UHFFFAOYSA-N 0.000 claims 2
• SDAONRBNOVJNMM-UHFFFAOYSA-N 1-[2-[2-[2-[4-(1-acetamidoethyl)anilino]-5-(trifluoromethyl)pyrimidin-4-yl]ethyl]phenyl]cyclopropane-1-carboxamide Chemical compound C1=CC(C(NC(C)=O)C)=CC=C1NC1=NC=C(C(F)(F)F)C(CCC=2C(=CC=CC=2)C2(CC2)C(N)=O)=N1 SDAONRBNOVJNMM-UHFFFAOYSA-N 0.000 claims 2
• TVHISEZISKGSQX-UHFFFAOYSA-N 1-[2-[2-[2-[4-(1-aminoethyl)anilino]-5-methylpyrimidin-4-yl]ethyl]phenyl]cyclopropane-1-carboxamide Chemical compound C1=CC(C(N)C)=CC=C1NC1=NC=C(C)C(CCC=2C(=CC=CC=2)C2(CC2)C(N)=O)=N1 TVHISEZISKGSQX-UHFFFAOYSA-N 0.000 claims 2
• FBOOAKYRDMGTPS-UHFFFAOYSA-N 1-[2-[2-[2-[[1-(1-methylpiperidin-4-yl)pyrazol-4-yl]amino]-5-(trifluoromethyl)pyrimidin-4-yl]ethyl]phenyl]cyclopropane-1-carboxamide Chemical compound C1CN(C)CCC1N1N=CC(NC=2N=C(CCC=3C(=CC=CC=3)C3(CC3)C(N)=O)C(=CN=2)C(F)(F)F)=C1 FBOOAKYRDMGTPS-UHFFFAOYSA-N 0.000 claims 2
• HQRUNGNEQLUCLO-UHFFFAOYSA-N 1-[2-[2-[2-[[1-(azetidin-3-yl)pyrazol-4-yl]amino]-5-chloropyrimidin-4-yl]ethyl]phenyl]cyclopropane-1-carboxamide Chemical compound C=1C=CC=C(CCC=2C(=CN=C(NC3=CN(N=C3)C3CNC3)N=2)Cl)C=1C1(C(=O)N)CC1 HQRUNGNEQLUCLO-UHFFFAOYSA-N 0.000 claims 2
• TUDRKGHTUBUSSR-UHFFFAOYSA-N 1-[2-[2-[2-[[6-(1-aminoethyl)pyridin-3-yl]amino]-5-(trifluoromethyl)pyrimidin-4-yl]ethyl]phenyl]cyclopropane-1-carboxamide Chemical compound C1=NC(C(N)C)=CC=C1NC1=NC=C(C(F)(F)F)C(CCC=2C(=CC=CC=2)C2(CC2)C(N)=O)=N1 TUDRKGHTUBUSSR-UHFFFAOYSA-N 0.000 claims 2
• DQQWJKOTZMUAHI-UHFFFAOYSA-N 1-[2-[2-[2-[[6-(1-methylpiperidin-4-yl)pyridin-3-yl]amino]-5-(trifluoromethyl)pyrimidin-4-yl]ethyl]phenyl]cyclopropane-1-carboxamide Chemical compound C1CN(C)CCC1C(N=C1)=CC=C1NC1=NC=C(C(F)(F)F)C(CCC=2C(=CC=CC=2)C2(CC2)C(N)=O)=N1 DQQWJKOTZMUAHI-UHFFFAOYSA-N 0.000 claims 2
• YAJCXJFEIUTXQV-UHFFFAOYSA-N 1-[2-[2-[2-[[6-(1-morpholin-4-ylethyl)pyridin-3-yl]amino]-5-(trifluoromethyl)pyrimidin-4-yl]ethyl]phenyl]cyclopropane-1-carboxamide Chemical compound C=1C=C(NC=2N=C(CCC=3C(=CC=CC=3)C3(CC3)C(N)=O)C(=CN=2)C(F)(F)F)C=NC=1C(C)N1CCOCC1 YAJCXJFEIUTXQV-UHFFFAOYSA-N 0.000 claims 2
• SWDNTDUABLQVFS-UHFFFAOYSA-N 1-[2-[2-[2-[[6-[1-(azetidin-1-yl)ethyl]pyridin-3-yl]amino]-5-(trifluoromethyl)pyrimidin-4-yl]ethyl]phenyl]cyclopropane-1-carboxamide Chemical compound C=1C=C(NC=2N=C(CCC=3C(=CC=CC=3)C3(CC3)C(N)=O)C(=CN=2)C(F)(F)F)C=NC=1C(C)N1CCC1 SWDNTDUABLQVFS-UHFFFAOYSA-N 0.000 claims 2
• QMYVWOJMXILKNP-UHFFFAOYSA-N 1-[2-[2-[2-[[6-[1-(methylamino)ethyl]pyridin-3-yl]amino]-5-(trifluoromethyl)pyrimidin-4-yl]ethyl]phenyl]cyclopropane-1-carboxamide Chemical compound C1=NC(C(C)NC)=CC=C1NC1=NC=C(C(F)(F)F)C(CCC=2C(=CC=CC=2)C2(CC2)C(N)=O)=N1 QMYVWOJMXILKNP-UHFFFAOYSA-N 0.000 claims 2
• JRVVFSGIVLNBFG-UHFFFAOYSA-N 1-[2-[2-[5-(trifluoromethyl)-2-[[6-(trifluoromethyl)pyridin-3-yl]amino]pyrimidin-4-yl]ethyl]phenyl]cyclopropane-1-carboxamide Chemical compound C=1C=CC=C(CCC=2C(=CN=C(NC=3C=NC(=CC=3)C(F)(F)F)N=2)C(F)(F)F)C=1C1(C(=O)N)CC1 JRVVFSGIVLNBFG-UHFFFAOYSA-N 0.000 claims 2
• PXZFWIYLLCBPCU-UHFFFAOYSA-N 1-[2-[2-[5-chloro-2-[(1,3-dimethylpyrazol-4-yl)amino]pyrimidin-4-yl]ethyl]phenyl]cyclopropane-1-carboxamide Chemical compound CC1=NN(C)C=C1NC1=NC=C(Cl)C(CCC=2C(=CC=CC=2)C2(CC2)C(N)=O)=N1 PXZFWIYLLCBPCU-UHFFFAOYSA-N 0.000 claims 2
• NEDBGDZTHCKDJL-UHFFFAOYSA-N 1-[2-[2-[5-chloro-2-[(1-methylpyrazol-3-yl)amino]pyrimidin-4-yl]ethyl]phenyl]cyclopropane-1-carboxamide Chemical compound CN1C=CC(NC=2N=C(CCC=3C(=CC=CC=3)C3(CC3)C(N)=O)C(Cl)=CN=2)=N1 NEDBGDZTHCKDJL-UHFFFAOYSA-N 0.000 claims 2
• GVZZEKBXTZEWOA-UHFFFAOYSA-N 1-[2-[2-[5-chloro-2-[(1-piperidin-4-ylpyrazol-4-yl)amino]pyrimidin-4-yl]ethyl]phenyl]cyclopropane-1-carboxamide Chemical compound C=1C=CC=C(CCC=2C(=CN=C(NC3=CN(N=C3)C3CCNCC3)N=2)Cl)C=1C1(C(=O)N)CC1 GVZZEKBXTZEWOA-UHFFFAOYSA-N 0.000 claims 2
• MPAJFLQBHBSWNO-UHFFFAOYSA-N 1-[2-[2-[5-chloro-2-[(1-propan-2-ylpyrazol-4-yl)amino]pyrimidin-4-yl]ethyl]phenyl]cyclopropane-1-carboxamide Chemical compound C1=NN(C(C)C)C=C1NC1=NC=C(Cl)C(CCC=2C(=CC=CC=2)C2(CC2)C(N)=O)=N1 MPAJFLQBHBSWNO-UHFFFAOYSA-N 0.000 claims 2
• UMAZVUGSOHOIKQ-UHFFFAOYSA-N 1-[2-[2-[5-chloro-2-[(1-pyrrolidin-3-ylpyrazol-4-yl)amino]pyrimidin-4-yl]ethyl]phenyl]cyclopropane-1-carboxamide Chemical compound C=1C=CC=C(CCC=2C(=CN=C(NC3=CN(N=C3)C3CNCC3)N=2)Cl)C=1C1(C(=O)N)CC1 UMAZVUGSOHOIKQ-UHFFFAOYSA-N 0.000 claims 2
• WQAZWPJKTOEOQF-UHFFFAOYSA-N 1-[2-[2-[5-chloro-2-[(5-methyl-1h-pyrazol-3-yl)amino]pyrimidin-4-yl]ethyl]phenyl]cyclopropane-1-carboxamide Chemical compound N1C(C)=CC(NC=2N=C(CCC=3C(=CC=CC=3)C3(CC3)C(N)=O)C(Cl)=CN=2)=N1 WQAZWPJKTOEOQF-UHFFFAOYSA-N 0.000 claims 2
• NSNISTVSHKRGGN-UHFFFAOYSA-N 1-[2-[2-[5-chloro-2-[(5-methyl-1h-pyrazol-4-yl)amino]pyrimidin-4-yl]ethyl]phenyl]cyclopropane-1-carboxamide Chemical compound CC1=NNC=C1NC1=NC=C(Cl)C(CCC=2C(=CC=CC=2)C2(CC2)C(N)=O)=N1 NSNISTVSHKRGGN-UHFFFAOYSA-N 0.000 claims 2
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