CA2882158A1 - Vegfr3 inhibitors - Google Patents
Vegfr3 inhibitors Download PDFInfo
- 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
- 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
- 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
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
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- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
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- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/04—Antineoplastic agents specific for metastasis
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
- C07D239/32—One oxygen, sulfur or nitrogen atom
- C07D239/42—One nitrogen atom
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing three or more hetero rings
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Oncology (AREA)
- Hematology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201261684202P | 2012-08-17 | 2012-08-17 | |
| US61/684,202 | 2012-08-17 | ||
| PCT/AU2013/000913 WO2014026243A1 (en) | 2012-08-17 | 2013-08-16 | Vegfr3 inhibitors |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2882158A1 true CA2882158A1 (en) | 2014-02-20 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2882158A Abandoned CA2882158A1 (en) | 2012-08-17 | 2013-08-16 | Vegfr3 inhibitors |
Country Status (8)
| Country | Link |
|---|---|
| US (2) | US20160009686A1 (enExample) |
| EP (1) | EP2885291A4 (enExample) |
| JP (1) | JP2015524826A (enExample) |
| CN (1) | CN104736533B (enExample) |
| AU (1) | AU2013302320A1 (enExample) |
| CA (1) | CA2882158A1 (enExample) |
| HK (1) | HK1209105A1 (enExample) |
| WO (1) | WO2014026243A1 (enExample) |
Families Citing this family (8)
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| EP2885292A4 (en) * | 2012-08-17 | 2015-07-01 | Cancer Therapeutics Crc Pty Ltd | VEGFR3 INHIBITORS |
| WO2015123722A1 (en) * | 2014-02-19 | 2015-08-27 | Bionomics Limited | Inhibitors |
| CN106588885B (zh) * | 2016-11-10 | 2019-03-19 | 浙江大学 | 2-取代芳环-嘧啶类衍生物及制备和应用 |
| CN112088003B (zh) * | 2017-12-20 | 2023-10-13 | 戴纳立制药公司 | 制备嘧啶基-4-氨基吡唑化合物的工艺 |
| BR112020013198A2 (pt) | 2017-12-29 | 2020-12-01 | Glycomimetics, Inc. | inibidores heterobifuncionais de e-selectina e galectina-3 |
| WO2020139962A1 (en) | 2018-12-27 | 2020-07-02 | Glycomimetics, Inc. | Heterobifunctional inhibitors of e-selectin and galectin-3 |
| CN109942616A (zh) * | 2019-04-18 | 2019-06-28 | 广东工业大学 | 一种含炔基的芳基酰胺类衍生物及其制备方法和应用 |
| WO2023073148A1 (en) * | 2021-10-29 | 2023-05-04 | Janssen Pharmaceutica Nv | Vascular endothelial growth factor receptor 3 as biomarker for bace2 activity |
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| GB9624482D0 (en) | 1995-12-18 | 1997-01-15 | Zeneca Phaema S A | Chemical compounds |
| WO1997030035A1 (en) | 1996-02-13 | 1997-08-21 | Zeneca Limited | Quinazoline derivatives as vegf inhibitors |
| PT885198E (pt) | 1996-03-05 | 2002-06-28 | Astrazeneca Ab | Derivados de 4-anilinoquinazolina |
| GB9718972D0 (en) | 1996-09-25 | 1997-11-12 | Zeneca Ltd | Chemical compounds |
| DE69837529T2 (de) | 1997-02-12 | 2007-07-26 | Electrophoretics Ltd., Cobham | Proteinmarker für lungenkrebs und deren verwendung |
| GB9714249D0 (en) | 1997-07-08 | 1997-09-10 | Angiogene Pharm Ltd | Vascular damaging agents |
| GB9900334D0 (en) | 1999-01-07 | 1999-02-24 | Angiogene Pharm Ltd | Tricylic vascular damaging agents |
| GB9900752D0 (en) | 1999-01-15 | 1999-03-03 | Angiogene Pharm Ltd | Benzimidazole vascular damaging agents |
| BRPI0017548B8 (pt) | 1999-02-10 | 2023-05-02 | Astrazeneca Ab | Composto |
| EE05330B1 (et) | 1999-11-05 | 2010-08-16 | Astrazeneca Ab | Kinasoliini derivaadid kui VEGF-i inhibiitorid |
| US6573293B2 (en) | 2000-02-15 | 2003-06-03 | Sugen, Inc. | Pyrrole substituted 2-indolinone protein kinase inhibitors |
| AU2001258628A1 (en) | 2000-05-31 | 2001-12-11 | Astrazeneca Ab | Indole derivatives with vascular damaging activity |
| UA73993C2 (uk) | 2000-06-06 | 2005-10-17 | Астразенека Аб | Хіназолінові похідні для лікування пухлин та фармацевтична композиція |
| BR0112225A (pt) | 2000-07-07 | 2003-05-06 | Angiogene Pharm Ltd | Composto, composição farmacêutica, uso de um composto, e, processo papa preparar um composto |
| MXPA02012905A (es) | 2000-07-07 | 2004-07-30 | Angiogene Pharm Ltd | Derivados de colquinol como agentes de dano vascular.. |
| ES2314106T3 (es) | 2001-10-17 | 2009-03-16 | BOEHRINGER INGELHEIM PHARMA GMBH & CO.KG | Derivados de pirimidina, agentes farmaceuticos que contiene dichos compuestos, uso y metodo para su obtencion. |
| WO2008008234A1 (en) * | 2006-07-07 | 2008-01-17 | Targegen, Inc. | 2-amino-5-substituted pyrimidine inhibitors |
| JP5311673B2 (ja) * | 2006-12-14 | 2013-10-09 | エグゼリクシス， インコーポレイテッド | Ｍｅｋ阻害剤の使用方法 |
| TW200922590A (en) * | 2007-09-10 | 2009-06-01 | Curis Inc | VEGFR inhibitors containing a zinc binding moiety |
| CN102272133A (zh) | 2008-11-06 | 2011-12-07 | 阿斯利康(瑞典)有限公司 | 淀粉样β的调节剂 |
| KR101639642B1 (ko) * | 2008-12-05 | 2016-07-14 | 애브비 바하마스 리미티드 | 암 치료에 사용하기 위한 키나제 억제제로서의 티에노［3,2-ｃ］피리딘 유도체 |
| WO2010111406A2 (en) | 2009-03-24 | 2010-09-30 | Myriad Pharmaceuticals, Inc. | Compounds and therapeutic uses thereof |
| EP2429520A1 (en) * | 2009-05-14 | 2012-03-21 | Boehringer Ingelheim International GmbH | New combination therapy in treatment of oncological and fibrotic diseases |
| DE102010034699A1 (de) * | 2010-08-18 | 2012-02-23 | Merck Patent Gmbh | Pyrimidinderivate |
| JP6185839B2 (ja) * | 2010-09-14 | 2017-08-23 | ノバルティス アーゲー | Ｂｒａｆ阻害薬とｖｅｇｆ阻害薬との組み合わせ |
| ES2691673T3 (es) | 2011-02-17 | 2018-11-28 | Cancer Therapeutics Crc Pty Limited | Inhibidores de Fak |
| JP5937112B2 (ja) | 2011-02-17 | 2016-06-22 | カンサー・セラピューティクス・シーアールシー・プロプライエタリー・リミテッドＣａｎｃｅｒ Ｔｈｅｒａｐｅｕｔｉｃｓ Ｃｒｃ Ｐｔｙ Ｌｉｍｉｔｅｄ | 選択的ｆａｋ阻害剤 |
| KR101682417B1 (ko) | 2011-02-25 | 2016-12-06 | 주식회사유한양행 | 다이아미노피리미딘 유도체 및 그의 제조방법 |
| EP2874625B1 (en) | 2012-07-17 | 2017-05-17 | Sanofi | Use of vegfr-3 inhibitors for treating hepatocellular carcinoma |
| WO2014027199A1 (en) * | 2012-08-14 | 2014-02-20 | Cancer Therapeutics Crc Pty Ltd | Fak and flt3 inhibitors |
| CN103113355B (zh) | 2013-02-27 | 2014-08-13 | 无锡爱内特生物科技有限公司 | 一种Bcr/Abl酪氨酸激酶抑制剂及其制备方法和在治疗慢性粒细胞白血病中的应用 |
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2013
- 2013-08-16 HK HK15109687.2A patent/HK1209105A1/xx unknown
- 2013-08-16 EP EP13829265.1A patent/EP2885291A4/en not_active Withdrawn
- 2013-08-16 WO PCT/AU2013/000913 patent/WO2014026243A1/en not_active Ceased
- 2013-08-16 CN CN201380052158.7A patent/CN104736533B/zh not_active Expired - Fee Related
- 2013-08-16 AU AU2013302320A patent/AU2013302320A1/en not_active Abandoned
- 2013-08-16 US US14/422,093 patent/US20160009686A1/en not_active Abandoned
- 2013-08-16 CA CA2882158A patent/CA2882158A1/en not_active Abandoned
- 2013-08-16 US US13/969,037 patent/US9238644B2/en not_active Expired - Fee Related
- 2013-08-16 JP JP2015526836A patent/JP2015524826A/ja active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| US9238644B2 (en) | 2016-01-19 |
| US20140073620A1 (en) | 2014-03-13 |
| EP2885291A1 (en) | 2015-06-24 |
| CN104736533A (zh) | 2015-06-24 |
| HK1209105A1 (en) | 2016-03-24 |
| JP2015524826A (ja) | 2015-08-27 |
| EP2885291A4 (en) | 2015-11-04 |
| AU2013302320A1 (en) | 2015-02-26 |
| US20160009686A1 (en) | 2016-01-14 |
| CN104736533B (zh) | 2016-12-07 |
| WO2014026243A1 (en) | 2014-02-20 |
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Legal Events
| Date | Code | Title | Description |
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| FZDE | Discontinued |
Effective date: 20180816 |