JP2016521706A5 - - Google Patents
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- Publication number
- JP2016521706A5 JP2016521706A5 JP2016517959A JP2016517959A JP2016521706A5 JP 2016521706 A5 JP2016521706 A5 JP 2016521706A5 JP 2016517959 A JP2016517959 A JP 2016517959A JP 2016517959 A JP2016517959 A JP 2016517959A JP 2016521706 A5 JP2016521706 A5 JP 2016521706A5
- Authority
- JP
- Japan
- Prior art keywords
- carboxamide
- indole
- yloxy
- methyl
- pyrimidin
- 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.)
- Granted
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- -1 CO 2 C 1 -C 6 alkyl Chemical group 0.000 claims description 134
- 239000000203 mixture Substances 0.000 claims description 132
- 150000003857 carboxamides Chemical class 0.000 claims description 20
- CQILOHWHIWNQOE-UHFFFAOYSA-N indole-1-carboxamide Chemical compound C1=CC=C2N(C(=O)N)C=CC2=C1 CQILOHWHIWNQOE-UHFFFAOYSA-N 0.000 claims description 20
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 16
- 229910052739 hydrogen Inorganic materials 0.000 claims description 14
- 239000001257 hydrogen Substances 0.000 claims description 14
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 12
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims description 12
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 12
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 claims description 12
- 239000000375 suspending agent Substances 0.000 claims description 11
- 210000004087 cornea Anatomy 0.000 claims description 10
- 125000000623 heterocyclic group Chemical group 0.000 claims description 10
- 239000004354 Hydroxyethyl cellulose Substances 0.000 claims description 8
- 229920000663 Hydroxyethyl cellulose Polymers 0.000 claims description 8
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 claims description 8
- 206010064930 age-related macular degeneration Diseases 0.000 claims description 8
- 235000019447 hydroxyethyl cellulose Nutrition 0.000 claims description 8
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 claims description 8
- 208000002780 macular degeneration Diseases 0.000 claims description 8
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 8
- 229920005862 polyol Polymers 0.000 claims description 8
- 150000003077 polyols Chemical class 0.000 claims description 8
- 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 description 8
- 206010029113 Neovascularisation Diseases 0.000 claims description 6
- 230000033115 angiogenesis Effects 0.000 claims description 6
- 239000000872 buffer Substances 0.000 claims description 6
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 6
- 229910052760 oxygen Inorganic materials 0.000 claims description 6
- 150000003839 salts Chemical class 0.000 claims description 6
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 5
- 239000003002 pH adjusting agent Substances 0.000 claims description 5
- 229910052717 sulfur Inorganic materials 0.000 claims description 5
- 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 claims description 4
- BTBUEUYNUDRHOZ-UHFFFAOYSA-N Borate Chemical group [O-]B([O-])[O-] BTBUEUYNUDRHOZ-UHFFFAOYSA-N 0.000 claims description 4
- 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 description 4
- 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 description 4
- 206010012689 Diabetic retinopathy Diseases 0.000 claims description 4
- 229930195725 Mannitol Natural products 0.000 claims description 4
- 239000002253 acid Substances 0.000 claims description 4
- 229910000147 aluminium phosphate Inorganic materials 0.000 claims description 4
- 229910052736 halogen Inorganic materials 0.000 claims description 4
- 150000002367 halogens Chemical class 0.000 claims description 4
- 125000001072 heteroaryl group Chemical group 0.000 claims description 4
- 125000005842 heteroatom Chemical group 0.000 claims description 4
- 239000004310 lactic acid Substances 0.000 claims description 4
- 235000014655 lactic acid Nutrition 0.000 claims description 4
- 239000000594 mannitol Substances 0.000 claims description 4
- 235000010355 mannitol Nutrition 0.000 claims description 4
- 125000001624 naphthyl group Chemical group 0.000 claims description 4
- 239000003755 preservative agent Substances 0.000 claims description 4
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 4
- 210000001525 retina Anatomy 0.000 claims description 4
- 208000004644 retinal vein occlusion Diseases 0.000 claims description 4
- 239000000600 sorbitol Substances 0.000 claims description 4
- 201000010099 disease Diseases 0.000 claims description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 3
- 230000002335 preservative effect Effects 0.000 claims description 3
- 125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 claims description 2
- XAGLYPURPUETCX-UHFFFAOYSA-N 2-[(6-methyl-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-4-yl)oxy]indole-1-carboxamide Chemical compound CC1CC2=C(N=CN=C2OC=2N(C3=CC=CC=C3C=2)C(=O)N)CN1 XAGLYPURPUETCX-UHFFFAOYSA-N 0.000 claims description 2
- UWKGCTDATIKZDI-UHFFFAOYSA-N 2-[(7-acetyl-6-methyl-6,8-dihydro-5H-pyrido[3,4-d]pyrimidin-4-yl)oxy]indole-1-carboxamide Chemical compound C(C)(=O)N1CC=2N=CN=C(C=2CC1C)OC=1N(C2=CC=CC=C2C=1)C(=O)N UWKGCTDATIKZDI-UHFFFAOYSA-N 0.000 claims description 2
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 claims description 2
- 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 description 2
- FGFZUHKYTRVORA-UHFFFAOYSA-N 4-fluoro-5-[6-(hydroxymethyl)pyrimidin-4-yl]oxy-n-[3-(trifluoromethyl)phenyl]indole-1-carboxamide Chemical compound C1=NC(CO)=CC(OC=2C(=C3C=CN(C3=CC=2)C(=O)NC=2C=C(C=CC=2)C(F)(F)F)F)=N1 FGFZUHKYTRVORA-UHFFFAOYSA-N 0.000 claims description 2
- 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 description 2
- 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 description 2
- 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 description 2
- 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 description 2
- 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 description 2
- 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 description 2
- 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 description 2
- 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 description 2
- 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 description 2
- SBRYGZQCYTWKIU-UHFFFAOYSA-N 5-(5,7-dihydrothieno[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=5CSCC=5N=CN=4)C=C3C=C2)=C1 SBRYGZQCYTWKIU-UHFFFAOYSA-N 0.000 claims description 2
- 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 description 2
- 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 description 2
- 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 description 2
- BVMXZRSDZZPQTD-UHFFFAOYSA-N 5-(6,7-dihydro-5h-pyrrolo[3,4-d]pyrimidin-4-yloxy)-4-fluoro-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=4CNCC=4N=CN=3)C(F)=C2C=C1 BVMXZRSDZZPQTD-UHFFFAOYSA-N 0.000 claims description 2
- 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 description 2
- 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 description 2
- 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 description 2
- 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 description 2
- 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 description 2
- 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 description 2
- 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 description 2
- 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 description 2
- 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 description 2
- 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 description 2
- 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 description 2
- 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 description 2
- XDCONQDBKMILCH-UHFFFAOYSA-N 5-[(6-acetyl-5,7-dihydropyrrolo[3,4-d]pyrimidin-4-yl)oxy]-n-[2-fluoro-3-(trifluoromethyl)phenyl]indole-1-carboxamide Chemical compound C=12CN(C(=O)C)CC2=NC=NC=1OC(C=C1C=C2)=CC=C1N2C(=O)NC1=CC=CC(C(F)(F)F)=C1F XDCONQDBKMILCH-UHFFFAOYSA-N 0.000 claims description 2
- 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 description 2
- 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 description 2
- 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 description 2
- 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 description 2
- WCJPOQLECAKCNT-UHFFFAOYSA-N 5-[(7-ethyl-6,8-dihydro-5h-pyrido[3,4-d]pyrimidin-4-yl)oxy]-n-[4-fluoro-3-(trifluoromethyl)phenyl]indole-1-carboxamide Chemical compound C1N(CC)CCC2=C1N=CN=C2OC(C=C1C=C2)=CC=C1N2C(=O)NC1=CC=C(F)C(C(F)(F)F)=C1 WCJPOQLECAKCNT-UHFFFAOYSA-N 0.000 claims description 2
- DZZVTNRAFOOIIL-UHFFFAOYSA-N 5-[2-(methylaminomethyl)pyridin-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)=C1 DZZVTNRAFOOIIL-UHFFFAOYSA-N 0.000 claims description 2
- BIPJNBSRIWQGOI-UHFFFAOYSA-N 5-[2-(methylaminomethyl)pyridin-4-yl]oxy-n-[3-(trifluoromethyl)phenyl]indole-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)=C1 BIPJNBSRIWQGOI-UHFFFAOYSA-N 0.000 claims description 2
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- 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 description 2
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- 150000003856 quaternary ammonium compounds Chemical class 0.000 claims description 2
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| 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 |
| 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 |
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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 |
| BR112021021175A2 (pt) | 2019-02-13 | 2021-12-14 | DEBx Medical Holding BV | Composições para remover tecidos necróticos ou infectados de lesões de superfície corporal e de cavidade oral |
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| US4027020A (en) | 1974-10-29 | 1977-05-31 | Millmaster Onyx Corporation | Randomly terminated capped polymers |
| US3931319A (en) | 1974-10-29 | 1976-01-06 | Millmaster Onyx Corporation | 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 |
| CA2814439A1 (en) | 2010-10-27 | 2012-05-03 | Novartis Ag | Dosing regimes for the treatment of ocular vascular disease |
| WO2012145460A2 (en) * | 2011-04-22 | 2012-10-26 | 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 |
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2014
- 2014-05-30 US US14/292,082 patent/US10174006B2/en not_active Expired - Fee Related
- 2014-06-04 HK HK16109315.1A patent/HK1221160A1/zh unknown
- 2014-06-04 KR KR1020157022071A patent/KR20160015192A/ko not_active Withdrawn
- 2014-06-04 WO PCT/US2014/040892 patent/WO2014197584A1/en not_active Ceased
- 2014-06-04 AU AU2014274955A patent/AU2014274955B2/en not_active Ceased
- 2014-06-04 JP JP2016517959A patent/JP6522592B2/ja not_active Expired - Fee Related
- 2014-06-04 CA CA2897949A patent/CA2897949A1/en not_active Abandoned
- 2014-06-04 EP EP14736523.3A patent/EP3003270A1/en not_active Withdrawn
- 2014-06-04 AR ARP140102179A patent/AR096473A1/es unknown
- 2014-06-04 BR BR112015019744A patent/BR112015019744A8/pt not_active Application Discontinuation
- 2014-06-04 MX MX2015014091A patent/MX2015014091A/es unknown
- 2014-06-04 CN CN201480011697.0A patent/CN105188663A/zh active Pending
- 2014-06-04 RU RU2015155604A patent/RU2015155604A/ru not_active Application Discontinuation
-
2015
- 2015-07-13 PH PH12015501555A patent/PH12015501555A1/en unknown
- 2015-11-26 CL CL2015003460A patent/CL2015003460A1/es unknown
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