RU2015155604A - Водные офтальмологические композиции для наружного применения, содержащие производное 1h-индол-1-карбоксамида, и их применение для лечения офтальмологического заболевания - Google Patents
Водные офтальмологические композиции для наружного применения, содержащие производное 1h-индол-1-карбоксамида, и их применение для лечения офтальмологического заболевания Download PDFInfo
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- RU2015155604A RU2015155604A RU2015155604A RU2015155604A RU2015155604A RU 2015155604 A RU2015155604 A RU 2015155604A RU 2015155604 A RU2015155604 A RU 2015155604A RU 2015155604 A RU2015155604 A RU 2015155604A RU 2015155604 A RU2015155604 A RU 2015155604A
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- RU
- Russia
- Prior art keywords
- carboxamide
- yloxy
- methyl
- indole
- pyrimidin
- Prior art date
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- 239000000203 mixture Substances 0.000 title claims 70
- CQILOHWHIWNQOE-UHFFFAOYSA-N indole-1-carboxamide Chemical class C1=CC=C2N(C(=O)N)C=CC2=C1 CQILOHWHIWNQOE-UHFFFAOYSA-N 0.000 title claims 10
- 201000010099 disease Diseases 0.000 title claims 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 title claims 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 title claims 2
- -1 CO 2 C 1 -C 6 alkyl Chemical group 0.000 claims 28
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims 8
- 229910052739 hydrogen Inorganic materials 0.000 claims 7
- 239000001257 hydrogen Substances 0.000 claims 7
- 230000001575 pathological effect Effects 0.000 claims 7
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims 6
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 claims 6
- 239000000375 suspending agent Substances 0.000 claims 6
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims 5
- 239000003002 pH adjusting agent Substances 0.000 claims 5
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims 4
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 claims 4
- 206010064930 age-related macular degeneration Diseases 0.000 claims 4
- 210000004087 cornea Anatomy 0.000 claims 4
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 claims 4
- 208000002780 macular degeneration Diseases 0.000 claims 4
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims 4
- 229920005862 polyol Polymers 0.000 claims 4
- 150000003077 polyols Chemical class 0.000 claims 4
- HFHDHCJBZVLPGP-UHFFFAOYSA-N schardinger α-dextrin Chemical class O1C(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(O)C2O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC2C(O)C(O)C1OC2CO HFHDHCJBZVLPGP-UHFFFAOYSA-N 0.000 claims 4
- 206010029113 Neovascularisation Diseases 0.000 claims 3
- 229910052736 halogen Inorganic materials 0.000 claims 3
- 150000002367 halogens Chemical class 0.000 claims 3
- 125000000623 heterocyclic group Chemical group 0.000 claims 3
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 3
- 229910052760 oxygen Inorganic materials 0.000 claims 3
- 210000001525 retina Anatomy 0.000 claims 3
- 150000003839 salts Chemical class 0.000 claims 3
- 229910052717 sulfur Inorganic materials 0.000 claims 3
- 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 claims 2
- XPIHPLVWOUDMPF-UHFFFAOYSA-N 5-[6-(methylaminomethyl)pyrimidin-4-yl]oxy-n-[1-methyl-5-(trifluoromethyl)pyrazol-3-yl]indole-1-carboxamide Chemical compound C1=NC(CNC)=CC(OC=2C=C3C=CN(C3=CC=2)C(=O)NC2=NN(C)C(=C2)C(F)(F)F)=N1 XPIHPLVWOUDMPF-UHFFFAOYSA-N 0.000 claims 2
- BTBUEUYNUDRHOZ-UHFFFAOYSA-N Borate Chemical group [O-]B([O-])[O-] BTBUEUYNUDRHOZ-UHFFFAOYSA-N 0.000 claims 2
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 claims 2
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 claims 2
- 206010012689 Diabetic retinopathy Diseases 0.000 claims 2
- 229930195725 Mannitol Natural products 0.000 claims 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims 2
- 229910000147 aluminium phosphate Inorganic materials 0.000 claims 2
- 230000033115 angiogenesis Effects 0.000 claims 2
- 229910052799 carbon Inorganic materials 0.000 claims 2
- 125000000753 cycloalkyl group Chemical group 0.000 claims 2
- 238000004299 exfoliation Methods 0.000 claims 2
- 235000011187 glycerol Nutrition 0.000 claims 2
- 125000001072 heteroaryl group Chemical group 0.000 claims 2
- 125000005842 heteroatom Chemical group 0.000 claims 2
- 239000004310 lactic acid Substances 0.000 claims 2
- 235000014655 lactic acid Nutrition 0.000 claims 2
- 239000000594 mannitol Substances 0.000 claims 2
- 235000010355 mannitol Nutrition 0.000 claims 2
- 125000001624 naphthyl group Chemical group 0.000 claims 2
- 239000003755 preservative agent Substances 0.000 claims 2
- 230000002335 preservative effect Effects 0.000 claims 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims 2
- 239000000600 sorbitol Substances 0.000 claims 2
- FYTIBTOYFZUROX-HNNXBMFYSA-N (6s)-4-[1-[(5-cyclopropyl-1,2-oxazol-3-yl)carbamoyl]indol-5-yl]oxy-n-ethyl-6-methyl-6,8-dihydro-5h-pyrido[3,4-d]pyrimidine-7-carboxamide Chemical compound CCNC(=O)N([C@H](CC1=2)C)CC1=NC=NC=2OC(C=C1C=C2)=CC=C1N2C(=O)NC(=NO1)C=C1C1CC1 FYTIBTOYFZUROX-HNNXBMFYSA-N 0.000 claims 1
- 125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 claims 1
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 1
- 125000004739 (C1-C6) alkylsulfonyl group Chemical group 0.000 claims 1
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims 1
- QXEURSHPNILVJO-UHFFFAOYSA-N 4-chloro-5-(6,7-dihydro-5h-pyrrolo[3,4-d]pyrimidin-4-yloxy)-n-(5-propan-2-yl-1,2-oxazol-3-yl)indole-1-carboxamide Chemical compound O1C(C(C)C)=CC(NC(=O)N2C3=CC=C(OC=4C=5CNCC=5N=CN=4)C(Cl)=C3C=C2)=N1 QXEURSHPNILVJO-UHFFFAOYSA-N 0.000 claims 1
- FSKMFOGKEJREJJ-UHFFFAOYSA-N 4-fluoro-5-(5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-4-yloxy)-n-[3-(trifluoromethyl)phenyl]indole-1-carboxamide Chemical compound C1=CC=2C(F)=C(OC=3C=4CCNCC=4N=CN=3)C=CC=2N1C(=O)NC1=CC=CC(C(F)(F)F)=C1 FSKMFOGKEJREJJ-UHFFFAOYSA-N 0.000 claims 1
- JSVVJBUEGUUJRR-UHFFFAOYSA-N 4-fluoro-5-[6-(methylaminomethyl)pyrimidin-4-yl]oxy-n-[5-(trifluoromethyl)-1h-pyrazol-3-yl]indole-1-carboxamide Chemical compound C1=NC(CNC)=CC(OC=2C(=C3C=CN(C3=CC=2)C(=O)NC2=NNC(=C2)C(F)(F)F)F)=N1 JSVVJBUEGUUJRR-UHFFFAOYSA-N 0.000 claims 1
- PERSGUPEEZKPPV-UHFFFAOYSA-N 4-methyl-5-[6-(methylaminomethyl)pyrimidin-4-yl]oxy-N-[1-methyl-5-(trifluoromethyl)pyrazol-3-yl]indole-1-carboxamide Chemical compound CNCc1cc(Oc2ccc3n(ccc3c2C)C(=O)Nc2cc(n(C)n2)C(F)(F)F)ncn1 PERSGUPEEZKPPV-UHFFFAOYSA-N 0.000 claims 1
- TYIBUHXCUGBDBD-AWEZNQCLSA-N 4-methyl-5-[[(6s)-6-methyl-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-4-yl]oxy]-n-(5-propan-2-yl-1,2-oxazol-3-yl)indole-1-carboxamide Chemical compound O1C(C(C)C)=CC(NC(=O)N2C3=CC=C(OC=4C=5C[C@H](C)NCC=5N=CN=4)C(C)=C3C=C2)=N1 TYIBUHXCUGBDBD-AWEZNQCLSA-N 0.000 claims 1
- XZGJJVFCLGBJES-LBPRGKRZSA-N 4-methyl-5-[[(6s)-6-methyl-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-4-yl]oxy]-n-[1-methyl-5-(trifluoromethyl)pyrazol-3-yl]indole-1-carboxamide Chemical compound C([C@@H](NC1)C)C2=C1N=CN=C2OC(C(=C1C=C2)C)=CC=C1N2C(=O)NC=1C=C(C(F)(F)F)N(C)N=1 XZGJJVFCLGBJES-LBPRGKRZSA-N 0.000 claims 1
- LJJLDTPVOBKYLW-ZDUSSCGKSA-N 4-methyl-5-[[(6s)-6-methyl-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-4-yl]oxy]-n-[5-[1-(trifluoromethyl)cyclopropyl]-1,2-oxazol-3-yl]indole-1-carboxamide Chemical compound C([C@@H](NC1)C)C2=C1N=CN=C2OC(C(=C1C=C2)C)=CC=C1N2C(=O)NC(=NO1)C=C1C1(C(F)(F)F)CC1 LJJLDTPVOBKYLW-ZDUSSCGKSA-N 0.000 claims 1
- BLNHHUHLQLPYEK-AWEZNQCLSA-N 4-methyl-n-[5-(1-methylcyclopropyl)-1,2-oxazol-3-yl]-5-[[(6s)-6-methyl-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-4-yl]oxy]indole-1-carboxamide Chemical compound C([C@@H](NC1)C)C2=C1N=CN=C2OC(C(=C1C=C2)C)=CC=C1N2C(=O)NC(=NO1)C=C1C1(C)CC1 BLNHHUHLQLPYEK-AWEZNQCLSA-N 0.000 claims 1
- RTNBWCYGJNXZBW-UHFFFAOYSA-N 5-(5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-4-yloxy)-n-[5-[1-(trifluoromethyl)cyclopropyl]-1,2-oxazol-3-yl]indole-1-carboxamide Chemical compound C=1C(NC(=O)N2C3=CC=C(OC=4C=5CCNCC=5N=CN=4)C=C3C=C2)=NOC=1C1(C(F)(F)F)CC1 RTNBWCYGJNXZBW-UHFFFAOYSA-N 0.000 claims 1
- KUOVYGJWXOPARC-UHFFFAOYSA-N 5-(5,7-dihydrothieno[3,4-d]pyrimidin-4-yloxy)-N-[1-methyl-5-(trifluoromethyl)pyrazol-3-yl]indole-1-carboxamide Chemical compound Cn1nc(NC(=O)n2ccc3cc(Oc4ncnc5CSCc45)ccc23)cc1C(F)(F)F KUOVYGJWXOPARC-UHFFFAOYSA-N 0.000 claims 1
- YMXKYXWPWJHZAV-UHFFFAOYSA-N 5-(5,7-dihydrothieno[3,4-d]pyrimidin-4-yloxy)-n-[2-fluoro-3-(trifluoromethyl)phenyl]indole-1-carboxamide Chemical compound C1=CC=C(C(F)(F)F)C(F)=C1NC(=O)N1C2=CC=C(OC=3C=4CSCC=4N=CN=3)C=C2C=C1 YMXKYXWPWJHZAV-UHFFFAOYSA-N 0.000 claims 1
- ZTBXTRLECRIMHA-UHFFFAOYSA-N 5-(5,7-dihydrothieno[3,4-d]pyrimidin-4-yloxy)-n-[5-(1-methylcyclopropyl)-1,2-oxazol-3-yl]indole-1-carboxamide Chemical compound C=1C(NC(=O)N2C3=CC=C(OC=4C=5CSCC=5N=CN=4)C=C3C=C2)=NOC=1C1(C)CC1 ZTBXTRLECRIMHA-UHFFFAOYSA-N 0.000 claims 1
- LYTBRTKAUNRWIC-UHFFFAOYSA-N 5-(5,7-dihydrothieno[3,4-d]pyrimidin-4-yloxy)-n-[5-[1-(trifluoromethyl)cyclopropyl]-1,2-oxazol-3-yl]indole-1-carboxamide Chemical compound C=1C(NC(=O)N2C3=CC=C(OC=4C=5CSCC=5N=CN=4)C=C3C=C2)=NOC=1C1(C(F)(F)F)CC1 LYTBRTKAUNRWIC-UHFFFAOYSA-N 0.000 claims 1
- NEMHNIVRHDHMPS-UHFFFAOYSA-N 5-(6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-4-yloxy)-N-(1-ethyl-5-methylpyrazol-3-yl)indole-1-carboxamide Chemical compound CCn1nc(NC(=O)n2ccc3cc(Oc4ncnc5CNCc45)ccc23)cc1C NEMHNIVRHDHMPS-UHFFFAOYSA-N 0.000 claims 1
- KEMACVMWDYIFSX-UHFFFAOYSA-N 5-(6,7-dihydro-5h-pyrrolo[3,4-d]pyrimidin-4-yloxy)-4-methyl-n-(5-propan-2-yl-1,2-oxazol-3-yl)indole-1-carboxamide Chemical compound O1C(C(C)C)=CC(NC(=O)N2C3=CC=C(OC=4C=5CNCC=5N=CN=4)C(C)=C3C=C2)=N1 KEMACVMWDYIFSX-UHFFFAOYSA-N 0.000 claims 1
- ABMNSLXSPONTJW-UHFFFAOYSA-N 5-(6,7-dihydro-5h-pyrrolo[3,4-d]pyrimidin-4-yloxy)-n-(4-methyl-5-propan-2-yl-1,2-oxazol-3-yl)indole-1-carboxamide Chemical compound CC1=C(C(C)C)ON=C1NC(=O)N1C2=CC=C(OC=3C=4CNCC=4N=CN=3)C=C2C=C1 ABMNSLXSPONTJW-UHFFFAOYSA-N 0.000 claims 1
- NFEGZWRWJVHIQY-UHFFFAOYSA-N 5-(6,7-dihydro-5h-pyrrolo[3,4-d]pyrimidin-4-yloxy)-n-(5-methyl-1-propan-2-ylpyrazol-3-yl)indole-1-carboxamide Chemical compound C1=C(C)N(C(C)C)N=C1NC(=O)N1C2=CC=C(OC=3C=4CNCC=4N=CN=3)C=C2C=C1 NFEGZWRWJVHIQY-UHFFFAOYSA-N 0.000 claims 1
- AWBYRRKKYLMHJC-UHFFFAOYSA-N 5-(6,7-dihydro-5h-pyrrolo[3,4-d]pyrimidin-4-yloxy)-n-[1-methyl-5-(trifluoromethyl)pyrazol-3-yl]indole-1-carboxamide Chemical compound C1=C(C(F)(F)F)N(C)N=C1NC(=O)N1C2=CC=C(OC=3C=4CNCC=4N=CN=3)C=C2C=C1 AWBYRRKKYLMHJC-UHFFFAOYSA-N 0.000 claims 1
- MZQWCIIFQKKAQS-UHFFFAOYSA-N 5-(6,7-dihydro-5h-pyrrolo[3,4-d]pyrimidin-4-yloxy)-n-[3-(trifluoromethyl)phenyl]indole-1-carboxamide Chemical compound FC(F)(F)C1=CC=CC(NC(=O)N2C3=CC=C(OC=4C=5CNCC=5N=CN=4)C=C3C=C2)=C1 MZQWCIIFQKKAQS-UHFFFAOYSA-N 0.000 claims 1
- HOBUPLCMPWNYAQ-UHFFFAOYSA-N 5-(6,7-dihydro-5h-pyrrolo[3,4-d]pyrimidin-4-yloxy)-n-[4-methyl-5-(1-methylcyclopropyl)-1,2-oxazol-3-yl]indole-1-carboxamide Chemical compound CC=1C(NC(=O)N2C3=CC=C(OC=4C=5CNCC=5N=CN=4)C=C3C=C2)=NOC=1C1(C)CC1 HOBUPLCMPWNYAQ-UHFFFAOYSA-N 0.000 claims 1
- NLPLUYRSIUXZHN-UHFFFAOYSA-N 5-(6,7-dihydro-5h-pyrrolo[3,4-d]pyrimidin-4-yloxy)-n-[5-[1-(trifluoromethyl)cyclopropyl]-1,2-oxazol-3-yl]indole-1-carboxamide Chemical compound C=1C(NC(=O)N2C3=CC=C(OC=4C=5CNCC=5N=CN=4)C=C3C=C2)=NOC=1C1(C(F)(F)F)CC1 NLPLUYRSIUXZHN-UHFFFAOYSA-N 0.000 claims 1
- ICWUFLXTRHJQRM-UHFFFAOYSA-N 5-[(6-acetyl-5,7-dihydropyrrolo[3,4-d]pyrimidin-4-yl)oxy]-4-methyl-n-[5-(1-methylcyclopropyl)-1,2-oxazol-3-yl]indole-1-carboxamide Chemical compound C=12CN(C(=O)C)CC2=NC=NC=1OC(C(=C1C=C2)C)=CC=C1N2C(=O)NC(=NO1)C=C1C1(C)CC1 ICWUFLXTRHJQRM-UHFFFAOYSA-N 0.000 claims 1
- BZBPDLCTQCATOP-UHFFFAOYSA-N 5-[(6-acetyl-5,7-dihydropyrrolo[3,4-d]pyrimidin-4-yl)oxy]-4-methyl-n-[5-[1-(trifluoromethyl)cyclopropyl]-1,2-oxazol-3-yl]indole-1-carboxamide Chemical compound C=12CN(C(=O)C)CC2=NC=NC=1OC(C(=C1C=C2)C)=CC=C1N2C(=O)NC(=NO1)C=C1C1(C(F)(F)F)CC1 BZBPDLCTQCATOP-UHFFFAOYSA-N 0.000 claims 1
- JEEFZPRJVIZNJN-UHFFFAOYSA-N 5-[(6-acetyl-5,7-dihydropyrrolo[3,4-d]pyrimidin-4-yl)oxy]-N-(5-cyclopropyl-1-methylpyrazol-3-yl)indole-1-carboxamide Chemical compound CC(=O)N1Cc2ncnc(Oc3ccc4n(ccc4c3)C(=O)Nc3cc(C4CC4)n(C)n3)c2C1 JEEFZPRJVIZNJN-UHFFFAOYSA-N 0.000 claims 1
- GWFFCLLCDHAOED-UHFFFAOYSA-N 5-[(6-acetyl-5,7-dihydropyrrolo[3,4-d]pyrimidin-4-yl)oxy]-N-[1-methyl-5-(trifluoromethyl)pyrazol-3-yl]indole-1-carboxamide Chemical compound CC(=O)N1Cc2ncnc(Oc3ccc4n(ccc4c3)C(=O)Nc3cc(n(C)n3)C(F)(F)F)c2C1 GWFFCLLCDHAOED-UHFFFAOYSA-N 0.000 claims 1
- BYIZTNXRPHXGHI-UHFFFAOYSA-N 5-[(6-acetyl-5,7-dihydropyrrolo[3,4-d]pyrimidin-4-yl)oxy]-n-(5-cyclopropyl-1,2-oxazol-3-yl)-4-methylindole-1-carboxamide Chemical compound C=12CN(C(=O)C)CC2=NC=NC=1OC(C(=C1C=C2)C)=CC=C1N2C(=O)NC(=NO1)C=C1C1CC1 BYIZTNXRPHXGHI-UHFFFAOYSA-N 0.000 claims 1
- YUVGBIYMUASXPM-UHFFFAOYSA-N 5-[(6-acetyl-5,7-dihydropyrrolo[3,4-d]pyrimidin-4-yl)oxy]-n-(5-cyclopropyl-1,2-oxazol-3-yl)indole-1-carboxamide Chemical compound C=12CN(C(=O)C)CC2=NC=NC=1OC(C=C1C=C2)=CC=C1N2C(=O)NC(=NO1)C=C1C1CC1 YUVGBIYMUASXPM-UHFFFAOYSA-N 0.000 claims 1
- DIWSXELTMJXYGQ-UHFFFAOYSA-N 5-[(6-acetyl-5,7-dihydropyrrolo[3,4-d]pyrimidin-4-yl)oxy]-n-(5-propan-2-yl-1,2-oxazol-3-yl)indole-1-carboxamide Chemical compound O1C(C(C)C)=CC(NC(=O)N2C3=CC=C(OC=4C=5CN(CC=5N=CN=4)C(C)=O)C=C3C=C2)=N1 DIWSXELTMJXYGQ-UHFFFAOYSA-N 0.000 claims 1
- WGODQOIMFUDLGT-UHFFFAOYSA-N 5-[(6-acetyl-5,7-dihydropyrrolo[3,4-d]pyrimidin-4-yl)oxy]-n-[5-(1-methylcyclopropyl)-1,2-oxazol-3-yl]indole-1-carboxamide Chemical compound C=12CN(C(=O)C)CC2=NC=NC=1OC(C=C1C=C2)=CC=C1N2C(=O)NC(=NO1)C=C1C1(C)CC1 WGODQOIMFUDLGT-UHFFFAOYSA-N 0.000 claims 1
- HGMYCARCPGFMBK-UHFFFAOYSA-N 5-[(6-methyl-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-4-yl)oxy]-n-(5-propan-2-yl-1h-pyrazol-3-yl)indole-1-carboxamide Chemical compound N1C(C(C)C)=CC(NC(=O)N2C3=CC=C(OC=4C=5CC(C)NCC=5N=CN=4)C=C3C=C2)=N1 HGMYCARCPGFMBK-UHFFFAOYSA-N 0.000 claims 1
- WGGSXHRZQATNAN-UHFFFAOYSA-N 5-[(6-methyl-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-4-yl)oxy]-n-[5-[1-(trifluoromethyl)cyclopropyl]-1,2-oxazol-3-yl]indole-1-carboxamide Chemical compound C1NC(C)CC2=C1N=CN=C2OC(C=C1C=C2)=CC=C1N2C(=O)NC(=NO1)C=C1C1(C(F)(F)F)CC1 WGGSXHRZQATNAN-UHFFFAOYSA-N 0.000 claims 1
- ASMFOWOLISPYBP-UHFFFAOYSA-N 5-[(7-acetyl-6,8-dihydro-5h-pyrido[3,4-d]pyrimidin-4-yl)oxy]-n-(5-cyclopropyl-1,2-oxazol-3-yl)indole-1-carboxamide Chemical compound C1N(C(=O)C)CCC2=C1N=CN=C2OC(C=C1C=C2)=CC=C1N2C(=O)NC(=NO1)C=C1C1CC1 ASMFOWOLISPYBP-UHFFFAOYSA-N 0.000 claims 1
- LKRDZDXYUCEKGZ-UHFFFAOYSA-N 5-[(7-methyl-6,8-dihydro-5h-pyrido[3,4-d]pyrimidin-4-yl)oxy]-n-[3-(trifluoromethyl)phenyl]indole-1-carboxamide Chemical compound C1N(C)CCC2=C1N=CN=C2OC(C=C1C=C2)=CC=C1N2C(=O)NC1=CC=CC(C(F)(F)F)=C1 LKRDZDXYUCEKGZ-UHFFFAOYSA-N 0.000 claims 1
- ZAVLXMXZSYYRKP-UHFFFAOYSA-N 5-[(7-propan-2-yl-6,8-dihydro-5h-pyrido[3,4-d]pyrimidin-4-yl)oxy]-n-[3-(trifluoromethyl)phenyl]indole-1-carboxamide Chemical compound C1N(C(C)C)CCC2=C1N=CN=C2OC(C=C1C=C2)=CC=C1N2C(=O)NC1=CC=CC(C(F)(F)F)=C1 ZAVLXMXZSYYRKP-UHFFFAOYSA-N 0.000 claims 1
- IIGMVRQZLODVCV-UHFFFAOYSA-N 5-[(7-propyl-6,8-dihydro-5h-pyrido[3,4-d]pyrimidin-4-yl)oxy]-n-[3-(trifluoromethyl)phenyl]indole-1-carboxamide Chemical compound C1N(CCC)CCC2=C1N=CN=C2OC(C=C1C=C2)=CC=C1N2C(=O)NC1=CC=CC(C(F)(F)F)=C1 IIGMVRQZLODVCV-UHFFFAOYSA-N 0.000 claims 1
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- YQJRMMABUZBLIF-AWEZNQCLSA-N methyl (6S)-6-methyl-4-[1-[[5-[1-(trifluoromethyl)cyclopropyl]-1,2-oxazol-3-yl]carbamoyl]indol-5-yl]oxy-6,8-dihydro-5H-pyrido[3,4-d]pyrimidine-7-carboxylate Chemical compound COC(=O)N1Cc2ncnc(Oc3ccc4n(ccc4c3)C(=O)Nc3cc(on3)C3(CC3)C(F)(F)F)c2C[C@@H]1C YQJRMMABUZBLIF-AWEZNQCLSA-N 0.000 claims 1
- OEYYZMVBVDBPBL-UHFFFAOYSA-N n-(1,5-dicyclopropylpyrazol-3-yl)-5-[6-(methylaminomethyl)pyrimidin-4-yl]oxyindole-1-carboxamide Chemical compound C1=NC(CNC)=CC(OC=2C=C3C=CN(C3=CC=2)C(=O)NC2=NN(C(C3CC3)=C2)C2CC2)=N1 OEYYZMVBVDBPBL-UHFFFAOYSA-N 0.000 claims 1
- HZQFOWOYRUCWMS-HNNXBMFYSA-N n-(1-tert-butyl-5-methylpyrazol-3-yl)-5-[[(6s)-6-methyl-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-4-yl]oxy]indole-1-carboxamide Chemical compound C([C@@H](NC1)C)C2=C1N=CN=C2OC(C=C1C=C2)=CC=C1N2C(=O)NC=1C=C(C)N(C(C)(C)C)N=1 HZQFOWOYRUCWMS-HNNXBMFYSA-N 0.000 claims 1
- ZXJSVQCLNCNZHX-HNNXBMFYSA-N n-(1-tert-butylpyrazol-3-yl)-4-methyl-5-[[(6s)-6-methyl-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-4-yl]oxy]indole-1-carboxamide Chemical compound C([C@@H](NC1)C)C2=C1N=CN=C2OC(C(=C1C=C2)C)=CC=C1N2C(=O)NC=1C=CN(C(C)(C)C)N=1 ZXJSVQCLNCNZHX-HNNXBMFYSA-N 0.000 claims 1
- RTCWIQXEZDXGDV-UHFFFAOYSA-N n-(1-tert-butylpyrazol-3-yl)-5-(5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-4-yloxy)indole-1-carboxamide Chemical compound CC(C)(C)N1C=CC(NC(=O)N2C3=CC=C(OC=4C=5CCNCC=5N=CN=4)C=C3C=C2)=N1 RTCWIQXEZDXGDV-UHFFFAOYSA-N 0.000 claims 1
- GMGGDLVTAWTZJQ-UHFFFAOYSA-N n-(1-tert-butylpyrazol-3-yl)-5-(6,7-dihydro-5h-pyrrolo[3,4-d]pyrimidin-4-yloxy)indole-1-carboxamide Chemical compound CC(C)(C)N1C=CC(NC(=O)N2C3=CC=C(OC=4C=5CNCC=5N=CN=4)C=C3C=C2)=N1 GMGGDLVTAWTZJQ-UHFFFAOYSA-N 0.000 claims 1
- OTLHPXPVTBTRNZ-UHFFFAOYSA-N n-(1-tert-butylpyrazol-3-yl)-5-[6-(methylaminomethyl)pyrimidin-4-yl]oxyindole-1-carboxamide Chemical compound C1=NC(CNC)=CC(OC=2C=C3C=CN(C3=CC=2)C(=O)NC2=NN(C=C2)C(C)(C)C)=N1 OTLHPXPVTBTRNZ-UHFFFAOYSA-N 0.000 claims 1
- CRIJHSHPELSNTD-HNNXBMFYSA-N n-(1-tert-butylpyrazol-3-yl)-5-[[(6s)-6-methyl-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-4-yl]oxy]indole-1-carboxamide Chemical compound C([C@@H](NC1)C)C2=C1N=CN=C2OC(C=C1C=C2)=CC=C1N2C(=O)NC=1C=CN(C(C)(C)C)N=1 CRIJHSHPELSNTD-HNNXBMFYSA-N 0.000 claims 1
- URUVMCCLSSBNTA-UHFFFAOYSA-N n-(4,4-dimethyl-5,6-dihydropyrrolo[1,2-b]pyrazol-2-yl)-5-[6-(methylsulfonylmethyl)pyrimidin-4-yl]oxyindole-1-carboxamide Chemical compound C1=C2C(C)(C)CCN2N=C1NC(=O)N(C1=CC=2)C=CC1=CC=2OC1=CC(CS(C)(=O)=O)=NC=N1 URUVMCCLSSBNTA-UHFFFAOYSA-N 0.000 claims 1
- MRMNXWKEXOJZLM-HNNXBMFYSA-N n-(4,4-dimethyl-5,6-dihydropyrrolo[1,2-b]pyrazol-2-yl)-5-[[(6s)-6-methyl-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-4-yl]oxy]indole-1-carboxamide Chemical compound C1=C2N(C(=O)NC3=NN4C(C(CC4)(C)C)=C3)C=CC2=CC(OC2=NC=NC3=C2C[C@@H](NC3)C)=C1 MRMNXWKEXOJZLM-HNNXBMFYSA-N 0.000 claims 1
- SUMDHQFMHJDWEC-ZDUSSCGKSA-N n-(5-cyclopropyl-1,2-oxazol-3-yl)-4-methyl-5-[[(6s)-6-methyl-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-4-yl]oxy]indole-1-carboxamide Chemical compound C([C@@H](NC1)C)C2=C1N=CN=C2OC(C(=C1C=C2)C)=CC=C1N2C(=O)NC(=NO1)C=C1C1CC1 SUMDHQFMHJDWEC-ZDUSSCGKSA-N 0.000 claims 1
- KXHFQOGUIWSNMX-HNNXBMFYSA-N n-(5-cyclopropyl-1,2-oxazol-3-yl)-4-methyl-5-[[(6s)-6-methyl-7-propanoyl-6,8-dihydro-5h-pyrido[3,4-d]pyrimidin-4-yl]oxy]indole-1-carboxamide Chemical compound CCC(=O)N([C@H](CC1=2)C)CC1=NC=NC=2OC(C(=C1C=C2)C)=CC=C1N2C(=O)NC(=NO1)C=C1C1CC1 KXHFQOGUIWSNMX-HNNXBMFYSA-N 0.000 claims 1
- KAWXURKOQZFLQB-UHFFFAOYSA-N n-(5-cyclopropyl-1,2-oxazol-3-yl)-5-(6,7-dihydro-5h-pyrrolo[3,4-d]pyrimidin-4-yloxy)-4-methylindole-1-carboxamide Chemical compound C1=CC=2C(C)=C(OC=3C=4CNCC=4N=CN=3)C=CC=2N1C(=O)NC(=NO1)C=C1C1CC1 KAWXURKOQZFLQB-UHFFFAOYSA-N 0.000 claims 1
- IFWNPAWLKUVJGK-UHFFFAOYSA-N n-(5-cyclopropyl-1,2-oxazol-3-yl)-5-(6,7-dihydro-5h-pyrrolo[3,4-d]pyrimidin-4-yloxy)indole-1-carboxamide Chemical compound C1=CC2=CC(OC=3C=4CNCC=4N=CN=3)=CC=C2N1C(=O)NC(=NO1)C=C1C1CC1 IFWNPAWLKUVJGK-UHFFFAOYSA-N 0.000 claims 1
- SOUHYNYJXMGGNP-UHFFFAOYSA-N n-(5-cyclopropyl-1,2-oxazol-3-yl)-5-[6-(tetrazol-2-ylmethyl)pyrimidin-4-yl]oxyindole-1-carboxamide Chemical compound C1=CC2=CC(OC=3N=CN=C(CN4N=NC=N4)C=3)=CC=C2N1C(=O)NC(=NO1)C=C1C1CC1 SOUHYNYJXMGGNP-UHFFFAOYSA-N 0.000 claims 1
- GRPZKRAJKSCZOO-CYBMUJFWSA-N n-(5-cyclopropyl-1,2-oxazol-3-yl)-5-[[(6r)-6-methyl-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-4-yl]oxy]indole-1-carboxamide Chemical compound C([C@H](NC1)C)C2=C1N=CN=C2OC(C=C1C=C2)=CC=C1N2C(=O)NC(=NO1)C=C1C1CC1 GRPZKRAJKSCZOO-CYBMUJFWSA-N 0.000 claims 1
- MWSYDHZCWUVTDH-AWEZNQCLSA-N n-(5-cyclopropyl-1,2-oxazol-3-yl)-5-[[(6s)-6,7-dimethyl-6,8-dihydro-5h-pyrido[3,4-d]pyrimidin-4-yl]oxy]indole-1-carboxamide Chemical compound C([C@@H](N(C1)C)C)C2=C1N=CN=C2OC(C=C1C=C2)=CC=C1N2C(=O)NC(=NO1)C=C1C1CC1 MWSYDHZCWUVTDH-AWEZNQCLSA-N 0.000 claims 1
- GRPZKRAJKSCZOO-ZDUSSCGKSA-N n-(5-cyclopropyl-1,2-oxazol-3-yl)-5-[[(6s)-6-methyl-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-4-yl]oxy]indole-1-carboxamide Chemical compound C([C@@H](NC1)C)C2=C1N=CN=C2OC(C=C1C=C2)=CC=C1N2C(=O)NC(=NO1)C=C1C1CC1 GRPZKRAJKSCZOO-ZDUSSCGKSA-N 0.000 claims 1
- AYLPHXBIOOZVAW-INIZCTEOSA-N n-(5-cyclopropyl-1,2-oxazol-3-yl)-5-[[(6s)-6-methyl-7-(2-methylpropanoyl)-6,8-dihydro-5h-pyrido[3,4-d]pyrimidin-4-yl]oxy]indole-1-carboxamide Chemical compound CC(C)C(=O)N([C@H](CC1=2)C)CC1=NC=NC=2OC(C=C1C=C2)=CC=C1N2C(=O)NC(=NO1)C=C1C1CC1 AYLPHXBIOOZVAW-INIZCTEOSA-N 0.000 claims 1
- NENZCXHTIICTFH-KRWDZBQOSA-N n-(5-cyclopropyl-1,2-oxazol-3-yl)-5-[[(6s)-6-methyl-7-(3-methylbutanoyl)-6,8-dihydro-5h-pyrido[3,4-d]pyrimidin-4-yl]oxy]indole-1-carboxamide Chemical compound CC(C)CC(=O)N([C@H](CC1=2)C)CC1=NC=NC=2OC(C=C1C=C2)=CC=C1N2C(=O)NC(=NO1)C=C1C1CC1 NENZCXHTIICTFH-KRWDZBQOSA-N 0.000 claims 1
- VWVGYFLGXIFKNY-SFHVURJKSA-N n-(5-cyclopropyl-1,2-oxazol-3-yl)-5-[[(6s)-6-methyl-7-(3-methylbutyl)-6,8-dihydro-5h-pyrido[3,4-d]pyrimidin-4-yl]oxy]indole-1-carboxamide Chemical compound CC(C)CCN([C@H](CC1=2)C)CC1=NC=NC=2OC(C=C1C=C2)=CC=C1N2C(=O)NC(=NO1)C=C1C1CC1 VWVGYFLGXIFKNY-SFHVURJKSA-N 0.000 claims 1
- FJDMNWCNRWFKEE-HNNXBMFYSA-N n-(5-cyclopropyl-1,2-oxazol-3-yl)-5-[[(6s)-6-methyl-7-[2-(methylamino)-2-oxoethyl]-6,8-dihydro-5h-pyrido[3,4-d]pyrimidin-4-yl]oxy]indole-1-carboxamide Chemical compound CNC(=O)CN([C@H](CC1=2)C)CC1=NC=NC=2OC(C=C1C=C2)=CC=C1N2C(=O)NC(=NO1)C=C1C1CC1 FJDMNWCNRWFKEE-HNNXBMFYSA-N 0.000 claims 1
- AIYPCMUPJGPBDZ-AWEZNQCLSA-N n-(5-cyclopropyl-1,2-oxazol-3-yl)-5-[[(6s)-6-methyl-7-methylsulfonyl-6,8-dihydro-5h-pyrido[3,4-d]pyrimidin-4-yl]oxy]indole-1-carboxamide Chemical compound C([C@@H](N(C1)S(C)(=O)=O)C)C2=C1N=CN=C2OC(C=C1C=C2)=CC=C1N2C(=O)NC(=NO1)C=C1C1CC1 AIYPCMUPJGPBDZ-AWEZNQCLSA-N 0.000 claims 1
- ABSWTUGWJJQOSZ-INIZCTEOSA-N n-(5-cyclopropyl-1,2-oxazol-3-yl)-5-[[(6s)-6-methyl-7-propan-2-yl-6,8-dihydro-5h-pyrido[3,4-d]pyrimidin-4-yl]oxy]indole-1-carboxamide Chemical compound CC(C)N([C@H](CC1=2)C)CC1=NC=NC=2OC(C=C1C=C2)=CC=C1N2C(=O)NC(=NO1)C=C1C1CC1 ABSWTUGWJJQOSZ-INIZCTEOSA-N 0.000 claims 1
- QHVQQSQAJCXBBM-HNNXBMFYSA-N n-(5-cyclopropyl-1,2-oxazol-3-yl)-5-[[(6s)-6-methyl-7-propanoyl-6,8-dihydro-5h-pyrido[3,4-d]pyrimidin-4-yl]oxy]indole-1-carboxamide Chemical compound CCC(=O)N([C@H](CC1=2)C)CC1=NC=NC=2OC(C=C1C=C2)=CC=C1N2C(=O)NC(=NO1)C=C1C1CC1 QHVQQSQAJCXBBM-HNNXBMFYSA-N 0.000 claims 1
- QTKLEUKHHKOAOT-INIZCTEOSA-N n-(5-cyclopropyl-1,2-oxazol-3-yl)-5-[[(6s)-6-methyl-7-propyl-6,8-dihydro-5h-pyrido[3,4-d]pyrimidin-4-yl]oxy]indole-1-carboxamide Chemical compound CCCN([C@H](CC1=2)C)CC1=NC=NC=2OC(C=C1C=C2)=CC=C1N2C(=O)NC(=NO1)C=C1C1CC1 QTKLEUKHHKOAOT-INIZCTEOSA-N 0.000 claims 1
- QZFOLNMCJLFDDY-HNNXBMFYSA-N n-(5-cyclopropyl-1,2-oxazol-3-yl)-5-[[(6s)-7-(2-hydroxyethyl)-6-methyl-6,8-dihydro-5h-pyrido[3,4-d]pyrimidin-4-yl]oxy]indole-1-carboxamide Chemical compound C([C@@H](N(C1)CCO)C)C2=C1N=CN=C2OC(C=C1C=C2)=CC=C1N2C(=O)NC(=NO1)C=C1C1CC1 QZFOLNMCJLFDDY-HNNXBMFYSA-N 0.000 claims 1
- MVJIXNZDBWTNCR-HNNXBMFYSA-N n-(5-cyclopropyl-1,2-oxazol-3-yl)-5-[[(6s)-7-ethyl-6-methyl-6,8-dihydro-5h-pyrido[3,4-d]pyrimidin-4-yl]oxy]indole-1-carboxamide Chemical compound CCN([C@H](CC1=2)C)CC1=NC=NC=2OC(C=C1C=C2)=CC=C1N2C(=O)NC(=NO1)C=C1C1CC1 MVJIXNZDBWTNCR-HNNXBMFYSA-N 0.000 claims 1
- RAYNXXKTXMROGO-UHFFFAOYSA-N n-(5-cyclopropyl-1,2-oxazol-3-yl)-5-[[6-(2-methylpropanoyl)-5,7-dihydropyrrolo[3,4-d]pyrimidin-4-yl]oxy]indole-1-carboxamide Chemical compound C=12CN(C(=O)C(C)C)CC2=NC=NC=1OC(C=C1C=C2)=CC=C1N2C(=O)NC(=NO1)C=C1C1CC1 RAYNXXKTXMROGO-UHFFFAOYSA-N 0.000 claims 1
- RPONGWQSZSNEGI-UHFFFAOYSA-N n-(5-cyclopropyl-1-ethylpyrazol-3-yl)-5-[6-(methylaminomethyl)pyrimidin-4-yl]oxyindole-1-carboxamide Chemical compound C1=C(C2CC2)N(CC)N=C1NC(=O)N(C1=CC=2)C=CC1=CC=2OC1=CC(CNC)=NC=N1 RPONGWQSZSNEGI-UHFFFAOYSA-N 0.000 claims 1
- MMEZSKUNRHGKAR-UHFFFAOYSA-N n-(5-cyclopropyl-1-methylpyrazol-3-yl)-5-[2-(methylaminomethyl)pyridin-4-yl]oxyindole-1-carboxamide Chemical compound C1=NC(CNC)=CC(OC=2C=C3C=CN(C3=CC=2)C(=O)NC2=NN(C)C(C3CC3)=C2)=C1 MMEZSKUNRHGKAR-UHFFFAOYSA-N 0.000 claims 1
- JHQIGDZFHKXPDR-UHFFFAOYSA-N n-(5-cyclopropyl-1-methylpyrazol-3-yl)-5-[6-(methylaminomethyl)pyrimidin-4-yl]oxyindole-1-carboxamide Chemical compound C1=NC(CNC)=CC(OC=2C=C3C=CN(C3=CC=2)C(=O)NC2=NN(C)C(C3CC3)=C2)=N1 JHQIGDZFHKXPDR-UHFFFAOYSA-N 0.000 claims 1
- XAPSXEJRUPBOER-UHFFFAOYSA-N n-(5-cyclopropyl-1-propan-2-ylpyrazol-3-yl)-5-[6-(methylaminomethyl)pyrimidin-4-yl]oxyindole-1-carboxamide Chemical compound C1=NC(CNC)=CC(OC=2C=C3C=CN(C3=CC=2)C(=O)NC2=NN(C(C3CC3)=C2)C(C)C)=N1 XAPSXEJRUPBOER-UHFFFAOYSA-N 0.000 claims 1
- JTGOIECHMKDPOK-INIZCTEOSA-N n-(5-cyclopropyl-1-propan-2-ylpyrazol-3-yl)-5-[[(6s)-6-methyl-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-4-yl]oxy]indole-1-carboxamide Chemical compound CC(C)N1N=C(NC(=O)N2C3=CC=C(OC=4C=5C[C@H](C)NCC=5N=CN=4)C=C3C=C2)C=C1C1CC1 JTGOIECHMKDPOK-INIZCTEOSA-N 0.000 claims 1
- XHAJXWNJRRTFIK-UHFFFAOYSA-N n-(5-cyclopropyl-1h-pyrazol-3-yl)-5-[(6-methyl-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-4-yl)oxy]indole-1-carboxamide Chemical compound C1NC(C)CC2=C1N=CN=C2OC(C=C1C=C2)=CC=C1N2C(=O)NC(=NN1)C=C1C1CC1 XHAJXWNJRRTFIK-UHFFFAOYSA-N 0.000 claims 1
- HCHRZWORJORBKT-UHFFFAOYSA-N n-(5-cyclopropyl-1h-pyrazol-3-yl)-5-[6-(methylaminomethyl)pyrimidin-4-yl]oxyindole-1-carboxamide Chemical compound C1=NC(CNC)=CC(OC=2C=C3C=CN(C3=CC=2)C(=O)NC2=NNC(=C2)C2CC2)=N1 HCHRZWORJORBKT-UHFFFAOYSA-N 0.000 claims 1
- DIGZJIQXGOXDOJ-UHFFFAOYSA-N n-(5-cyclopropyl-4-methyl-1,2-oxazol-3-yl)-5-(6,7-dihydro-5h-pyrrolo[3,4-d]pyrimidin-4-yloxy)indole-1-carboxamide Chemical compound CC=1C(NC(=O)N2C3=CC=C(OC=4C=5CNCC=5N=CN=4)C=C3C=C2)=NOC=1C1CC1 DIGZJIQXGOXDOJ-UHFFFAOYSA-N 0.000 claims 1
- JOTIUJWEBHKJJC-UHFFFAOYSA-N n-(5-propan-2-yl-1,2-oxazol-3-yl)-5-[6-(tetrazol-2-ylmethyl)pyrimidin-4-yl]oxyindole-1-carboxamide Chemical compound O1C(C(C)C)=CC(NC(=O)N2C3=CC=C(OC=4N=CN=C(CN5N=NC=N5)C=4)C=C3C=C2)=N1 JOTIUJWEBHKJJC-UHFFFAOYSA-N 0.000 claims 1
- YRPVJGFEIBZOGU-UHFFFAOYSA-N n-(5-tert-butyl-1,2-oxazol-3-yl)-4-fluoro-5-(5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-4-yloxy)indole-1-carboxamide Chemical compound O1C(C(C)(C)C)=CC(NC(=O)N2C3=CC=C(OC=4C=5CCNCC=5N=CN=4)C(F)=C3C=C2)=N1 YRPVJGFEIBZOGU-UHFFFAOYSA-N 0.000 claims 1
- GKILTERPEQPMQT-UHFFFAOYSA-N n-(5-tert-butyl-1,2-oxazol-3-yl)-5-[(6-methyl-5,7-dihydropyrrolo[3,4-d]pyrimidin-4-yl)oxy]indole-1-carboxamide Chemical compound C=12CN(C)CC2=NC=NC=1OC(C=C1C=C2)=CC=C1N2C(=O)NC=1C=C(C(C)(C)C)ON=1 GKILTERPEQPMQT-UHFFFAOYSA-N 0.000 claims 1
- WUZPWGPRTDZCMN-UHFFFAOYSA-N n-(5-tert-butyl-4-methyl-1,2-oxazol-3-yl)-5-(6,7-dihydro-5h-pyrrolo[3,4-d]pyrimidin-4-yloxy)indole-1-carboxamide Chemical compound O1C(C(C)(C)C)=C(C)C(NC(=O)N2C3=CC=C(OC=4C=5CNCC=5N=CN=4)C=C3C=C2)=N1 WUZPWGPRTDZCMN-UHFFFAOYSA-N 0.000 claims 1
- JJHZWXPGYFADRV-ZDUSSCGKSA-N n-[1-ethyl-5-(trifluoromethyl)pyrazol-3-yl]-5-[[(6s)-6-methyl-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-4-yl]oxy]indole-1-carboxamide Chemical compound C1=C(C(F)(F)F)N(CC)N=C1NC(=O)N1C2=CC=C(OC=3C=4C[C@H](C)NCC=4N=CN=3)C=C2C=C1 JJHZWXPGYFADRV-ZDUSSCGKSA-N 0.000 claims 1
- BYSIUBHELXQEDG-UHFFFAOYSA-N n-[1-methyl-5-(1-methylcyclopropyl)pyrazol-3-yl]-5-(5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-4-yloxy)indole-1-carboxamide Chemical compound CN1N=C(NC(=O)N2C3=CC=C(OC=4C=5CCNCC=5N=CN=4)C=C3C=C2)C=C1C1(C)CC1 BYSIUBHELXQEDG-UHFFFAOYSA-N 0.000 claims 1
- XSASTOMINSRXMM-HNNXBMFYSA-N n-[1-methyl-5-(1-methylcyclopropyl)pyrazol-3-yl]-5-[[(6s)-6-methyl-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-4-yl]oxy]indole-1-carboxamide Chemical compound C([C@@H](NC1)C)C2=C1N=CN=C2OC(C=C1C=C2)=CC=C1N2C(=O)NC(=NN1C)C=C1C1(C)CC1 XSASTOMINSRXMM-HNNXBMFYSA-N 0.000 claims 1
- PGHNRLMKTNYWMX-UHFFFAOYSA-N n-[2-fluoro-3-(trifluoromethyl)phenyl]-5-[6-(methylaminomethyl)pyrimidin-4-yl]oxyindole-1-carboxamide Chemical compound C1=NC(CNC)=CC(OC=2C=C3C=CN(C3=CC=2)C(=O)NC=2C(=C(C=CC=2)C(F)(F)F)F)=N1 PGHNRLMKTNYWMX-UHFFFAOYSA-N 0.000 claims 1
- HJPXIQLHMYRVJE-UHFFFAOYSA-N n-[2-fluoro-3-(trifluoromethyl)phenyl]-5-[6-(methylsulfonylmethyl)pyrimidin-4-yl]oxyindole-1-carboxamide Chemical compound C1=NC(CS(=O)(=O)C)=CC(OC=2C=C3C=CN(C3=CC=2)C(=O)NC=2C(=C(C=CC=2)C(F)(F)F)F)=N1 HJPXIQLHMYRVJE-UHFFFAOYSA-N 0.000 claims 1
- HGKNKHJUWPWRBK-UHFFFAOYSA-N n-[2-fluoro-5-(trifluoromethyl)phenyl]-5-(5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-4-yloxy)indole-1-carboxamide Chemical compound FC1=CC=C(C(F)(F)F)C=C1NC(=O)N1C2=CC=C(OC=3C=4CCNCC=4N=CN=3)C=C2C=C1 HGKNKHJUWPWRBK-UHFFFAOYSA-N 0.000 claims 1
- BZLHTUUSFSJYMO-UHFFFAOYSA-N n-[4-chloro-5-(1-methylcyclopropyl)-1,2-oxazol-3-yl]-5-(6,7-dihydro-5h-pyrrolo[3,4-d]pyrimidin-4-yloxy)indole-1-carboxamide Chemical compound O1N=C(NC(=O)N2C3=CC=C(OC=4C=5CNCC=5N=CN=4)C=C3C=C2)C(Cl)=C1C1(C)CC1 BZLHTUUSFSJYMO-UHFFFAOYSA-N 0.000 claims 1
- OQCQXSQLVCYSLF-UHFFFAOYSA-N n-[4-fluoro-3-(trifluoromethyl)phenyl]-5-[6-(methylaminomethyl)pyrimidin-4-yl]oxyindole-1-carboxamide Chemical compound C1=NC(CNC)=CC(OC=2C=C3C=CN(C3=CC=2)C(=O)NC=2C=C(C(F)=CC=2)C(F)(F)F)=N1 OQCQXSQLVCYSLF-UHFFFAOYSA-N 0.000 claims 1
- KGLDIAWBXBMFEB-UHFFFAOYSA-N n-[4-fluoro-3-(trifluoromethyl)phenyl]-5-[6-(methylsulfonylmethyl)pyrimidin-4-yl]oxyindole-1-carboxamide Chemical compound C1=NC(CS(=O)(=O)C)=CC(OC=2C=C3C=CN(C3=CC=2)C(=O)NC=2C=C(C(F)=CC=2)C(F)(F)F)=N1 KGLDIAWBXBMFEB-UHFFFAOYSA-N 0.000 claims 1
- RTJNJSZZQKVPCN-UHFFFAOYSA-N n-[4-fluoro-3-(trifluoromethyl)phenyl]-5-[6-(tetrazol-2-ylmethyl)pyrimidin-4-yl]oxyindole-1-carboxamide Chemical compound C1=C(C(F)(F)F)C(F)=CC=C1NC(=O)N1C2=CC=C(OC=3N=CN=C(CN4N=NC=N4)C=3)C=C2C=C1 RTJNJSZZQKVPCN-UHFFFAOYSA-N 0.000 claims 1
- MZWRVQDURCOJRF-UHFFFAOYSA-N n-[5-(1-methylcyclopropyl)-1,2-oxazol-3-yl]-5-[6-(tetrazol-2-ylmethyl)pyrimidin-4-yl]oxyindole-1-carboxamide Chemical compound C=1C(NC(=O)N2C3=CC=C(OC=4N=CN=C(CN5N=NC=N5)C=4)C=C3C=C2)=NOC=1C1(C)CC1 MZWRVQDURCOJRF-UHFFFAOYSA-N 0.000 claims 1
- IJSLAHMBRWCXBJ-UHFFFAOYSA-N n-[5-(1-methylcyclopropyl)-1,2-oxazol-3-yl]-5-[[6-(2-methylpropanoyl)-5,7-dihydropyrrolo[3,4-d]pyrimidin-4-yl]oxy]indole-1-carboxamide Chemical compound C=12CN(C(=O)C(C)C)CC2=NC=NC=1OC(C=C1C=C2)=CC=C1N2C(=O)NC(=NO1)C=C1C1(C)CC1 IJSLAHMBRWCXBJ-UHFFFAOYSA-N 0.000 claims 1
- 230000001613 neoplastic effect Effects 0.000 claims 1
- 239000002357 osmotic agent Substances 0.000 claims 1
- 201000007914 proliferative diabetic retinopathy Diseases 0.000 claims 1
- 108060006633 protein kinase Proteins 0.000 claims 1
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- 210000001957 retinal vein Anatomy 0.000 claims 1
- 201000000306 sarcoidosis Diseases 0.000 claims 1
- 229920006395 saturated elastomer Polymers 0.000 claims 1
- SNOOUWRIMMFWNE-UHFFFAOYSA-M sodium;6-[(3,4,5-trimethoxybenzoyl)amino]hexanoate Chemical compound [Na+].COC1=CC(C(=O)NCCCCCC([O-])=O)=CC(OC)=C1OC SNOOUWRIMMFWNE-UHFFFAOYSA-M 0.000 claims 1
- 239000004094 surface-active agent Substances 0.000 claims 1
- 208000006379 syphilis Diseases 0.000 claims 1
- ODLHGICHYURWBS-LKONHMLTSA-N trappsol cyclo Chemical compound CC(O)COC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)COCC(O)C)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1COCC(C)O ODLHGICHYURWBS-LKONHMLTSA-N 0.000 claims 1
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Classifications
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- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
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- 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
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- 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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- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
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- C07D495/04—Ortho-condensed systems
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D519/00—Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
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Applications Claiming Priority (5)
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| US201361831834P | 2013-06-06 | 2013-06-06 | |
| US61/831,834 | 2013-06-06 | ||
| US14/292,082 US10174006B2 (en) | 2013-06-06 | 2014-05-30 | Topical aqueous ophthalmic compositions containing a 1H-indole-1-carboxamide derivative and use thereof for treatment of ophthalmic disease |
| US14/292,082 | 2014-05-30 | ||
| PCT/US2014/040892 WO2014197584A1 (en) | 2013-06-06 | 2014-06-04 | Topical aqueous ophthalmic compositions containing a 1h-indole-1-carboxamide derivative and use thereof for treatment of ophthalmic disease |
Publications (2)
| Publication Number | Publication Date |
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| RU2015155604A true RU2015155604A (ru) | 2017-07-17 |
| RU2015155604A3 RU2015155604A3 (enExample) | 2018-05-28 |
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| RU2015155604A RU2015155604A (ru) | 2013-06-06 | 2014-06-04 | Водные офтальмологические композиции для наружного применения, содержащие производное 1h-индол-1-карбоксамида, и их применение для лечения офтальмологического заболевания |
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| EP (1) | EP3003270A1 (enExample) |
| JP (1) | JP6522592B2 (enExample) |
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| US10174006B2 (en) | 2013-06-06 | 2019-01-08 | Novartis Ag | Topical aqueous ophthalmic compositions containing a 1H-indole-1-carboxamide derivative and use thereof for treatment of ophthalmic disease |
| GB2561355A (en) * | 2017-04-10 | 2018-10-17 | Eaststone Ltd | Pharmaceutical composition and a method for manufacturing the same |
| KR102125256B1 (ko) * | 2018-12-28 | 2020-07-07 | 현대바이오사이언스 주식회사 | 점안용 담체 복합체, 이를 포함하는 약학 조성물, 및 약학 조성물의 제조방법 |
| PT3923923T (pt) | 2019-02-13 | 2024-06-20 | DEBx Medical Holding BV | Composições para remoção de tecidos necróticos ou infectados de lesões da superfície corporal e da cavidade oral |
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| US3931319A (en) | 1974-10-29 | 1976-01-06 | Millmaster Onyx Corporation | Capped polymers |
| US4027020A (en) | 1974-10-29 | 1977-05-31 | Millmaster Onyx Corporation | Randomly terminated capped polymers |
| US4525346A (en) | 1981-09-28 | 1985-06-25 | Alcon Laboratories, Inc. | Aqueous antimicrobial ophthalmic solutions |
| US4407791A (en) | 1981-09-28 | 1983-10-04 | Alcon Laboratories, Inc. | Ophthalmic solutions |
| US4836986A (en) | 1984-09-28 | 1989-06-06 | Bausch & Lomb Incorporated | Disinfecting and preserving systems and methods of use |
| US5037647A (en) | 1988-09-15 | 1991-08-06 | Alcon Laboratories, Inc. | Aqueous antimicrobial opthalmic solutions comprised of quaternary ammonium compound, citric acid, citrate and sodium chloride |
| US5145643A (en) | 1990-01-05 | 1992-09-08 | Allergan, Inc. | Nonoxidative ophthalmic compositions and methods for preserving and using same |
| US5362758A (en) * | 1992-09-18 | 1994-11-08 | Pfizer Inc. | Ophthalmic piroxicam solution |
| US5300287A (en) | 1992-11-04 | 1994-04-05 | Alcon Laboratories, Inc. | Polymeric antimicrobials and their use in pharmaceutical compositions |
| TW434023B (en) | 1995-09-18 | 2001-05-16 | Novartis Ag | Preserved ophthalmic composition |
| US5800807A (en) * | 1997-01-29 | 1998-09-01 | Bausch & Lomb Incorporated | Ophthalmic compositions including glycerin and propylene glycol |
| GB9714917D0 (en) | 1997-07-17 | 1997-09-17 | Hodgkinson William | Can cleaning and delivery apparatus |
| EP0938896A1 (en) * | 1998-01-15 | 1999-09-01 | Novartis AG | Autoclavable pharmaceutical compositions containing a chelating agent |
| US20060141059A1 (en) * | 2004-12-27 | 2006-06-29 | Alcon, Inc. | Self-preserved ophthalmic pharmaceutical compositions containing tobramycin |
| JP5349317B2 (ja) * | 2007-09-28 | 2013-11-20 | ロート製薬株式会社 | 眼科用組成物 |
| JO3265B1 (ar) | 2008-12-09 | 2018-09-16 | Novartis Ag | مثبطات بيريديلوكسى اندولات vegf-r2 واستخدامها لعلاج المرض |
| EP2196941A1 (fr) | 2008-12-11 | 2010-06-16 | Gemalto SA | Dispositif de connexion à une carte à puce |
| BR112013009701A2 (pt) | 2010-10-27 | 2016-07-19 | Novartis Ag | regimes de dosagem para o tratamento de doença vascular ocular |
| EP2699228A2 (en) * | 2011-04-22 | 2014-02-26 | Alcon Research, Ltd. | Ophthalmic composition with a viscosity enhancement system having two different viscosity enhancing agents |
| US10174006B2 (en) | 2013-06-06 | 2019-01-08 | Novartis Ag | Topical aqueous ophthalmic compositions containing a 1H-indole-1-carboxamide derivative and use thereof for treatment of ophthalmic disease |
-
2014
- 2014-05-30 US US14/292,082 patent/US10174006B2/en not_active Expired - Fee Related
- 2014-06-04 RU RU2015155604A patent/RU2015155604A/ru not_active Application Discontinuation
- 2014-06-04 CN CN201480011697.0A patent/CN105188663A/zh active Pending
- 2014-06-04 AU AU2014274955A patent/AU2014274955B2/en not_active Ceased
- 2014-06-04 CA CA2897949A patent/CA2897949A1/en not_active Abandoned
- 2014-06-04 KR KR1020157022071A patent/KR20160015192A/ko not_active Withdrawn
- 2014-06-04 EP EP14736523.3A patent/EP3003270A1/en not_active Withdrawn
- 2014-06-04 MX MX2015014091A patent/MX2015014091A/es unknown
- 2014-06-04 WO PCT/US2014/040892 patent/WO2014197584A1/en not_active Ceased
- 2014-06-04 HK HK16109315.1A patent/HK1221160A1/zh unknown
- 2014-06-04 BR BR112015019744A patent/BR112015019744A8/pt not_active Application Discontinuation
- 2014-06-04 AR ARP140102179A patent/AR096473A1/es unknown
- 2014-06-04 JP JP2016517959A patent/JP6522592B2/ja not_active Expired - Fee Related
-
2015
- 2015-07-13 PH PH12015501555A patent/PH12015501555A1/en unknown
- 2015-11-26 CL CL2015003460A patent/CL2015003460A1/es unknown
Also Published As
| Publication number | Publication date |
|---|---|
| WO2014197584A1 (en) | 2014-12-11 |
| BR112015019744A2 (pt) | 2017-07-18 |
| CN105188663A (zh) | 2015-12-23 |
| AR096473A1 (es) | 2015-12-30 |
| CL2015003460A1 (es) | 2016-07-08 |
| EP3003270A1 (en) | 2016-04-13 |
| RU2015155604A3 (enExample) | 2018-05-28 |
| KR20160015192A (ko) | 2016-02-12 |
| MX2015014091A (es) | 2015-12-15 |
| AU2014274955B2 (en) | 2019-02-21 |
| CA2897949A1 (en) | 2014-12-11 |
| JP2016521706A (ja) | 2016-07-25 |
| AU2014274955A1 (en) | 2015-07-16 |
| US20140364392A1 (en) | 2014-12-11 |
| BR112015019744A8 (pt) | 2019-11-05 |
| HK1221160A1 (zh) | 2017-05-26 |
| US10174006B2 (en) | 2019-01-08 |
| PH12015501555A1 (en) | 2015-09-21 |
| JP6522592B2 (ja) | 2019-05-29 |
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