CA2897949A1 - Topical aqueous ophthalmic compositions containing a 1h-indole-1-carboxamide derivative and use thereof for treatment of ophthalmic disease - Google Patents
Topical aqueous ophthalmic compositions containing a 1h-indole-1-carboxamide derivative and use thereof for treatment of ophthalmic disease Download PDFInfo
- Publication number
- CA2897949A1 CA2897949A1 CA2897949A CA2897949A CA2897949A1 CA 2897949 A1 CA2897949 A1 CA 2897949A1 CA 2897949 A CA2897949 A CA 2897949A CA 2897949 A CA2897949 A CA 2897949A CA 2897949 A1 CA2897949 A1 CA 2897949A1
- Authority
- CA
- Canada
- Prior art keywords
- indole
- carboxamide
- methyl
- yloxy
- 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.)
- Abandoned
Links
- 239000000203 mixture Substances 0.000 title claims abstract description 309
- CQILOHWHIWNQOE-UHFFFAOYSA-N indole-1-carboxamide Chemical class C1=CC=C2N(C(=O)N)C=CC2=C1 CQILOHWHIWNQOE-UHFFFAOYSA-N 0.000 title claims abstract description 103
- 230000000699 topical effect Effects 0.000 title abstract description 22
- 201000010099 disease Diseases 0.000 title abstract description 18
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 title abstract description 18
- 238000011282 treatment Methods 0.000 title abstract description 13
- 206010064930 age-related macular degeneration Diseases 0.000 claims abstract description 17
- 208000002780 macular degeneration Diseases 0.000 claims abstract description 17
- 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 abstract description 16
- 229920000663 Hydroxyethyl cellulose Polymers 0.000 claims description 52
- 235000019447 hydroxyethyl cellulose Nutrition 0.000 claims description 52
- 239000004354 Hydroxyethyl cellulose Substances 0.000 claims description 47
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 46
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 claims description 46
- 229920005862 polyol Polymers 0.000 claims description 34
- 150000003077 polyols Chemical class 0.000 claims description 32
- 239000002253 acid Substances 0.000 claims description 29
- 239000004615 ingredient Substances 0.000 claims description 29
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 25
- 239000003795 chemical substances by application Substances 0.000 claims description 25
- -1 CO2C1-C6alkyl Chemical group 0.000 claims description 24
- 239000000375 suspending agent Substances 0.000 claims description 24
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims description 22
- 239000001257 hydrogen Substances 0.000 claims description 21
- 229910052739 hydrogen Inorganic materials 0.000 claims description 21
- 150000003839 salts Chemical class 0.000 claims description 20
- 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 20
- 238000010979 pH adjustment Methods 0.000 claims description 19
- 239000003755 preservative agent Substances 0.000 claims description 19
- 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 18
- 210000001525 retina Anatomy 0.000 claims description 18
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 17
- 229930195725 Mannitol Natural products 0.000 claims description 16
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 claims description 16
- 229960000686 benzalkonium chloride Drugs 0.000 claims description 16
- CADWTSSKOVRVJC-UHFFFAOYSA-N benzyl(dimethyl)azanium;chloride Chemical compound [Cl-].C[NH+](C)CC1=CC=CC=C1 CADWTSSKOVRVJC-UHFFFAOYSA-N 0.000 claims description 16
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 16
- 235000010355 mannitol Nutrition 0.000 claims description 16
- 239000000594 mannitol Substances 0.000 claims description 16
- 230000002335 preservative effect Effects 0.000 claims description 16
- 210000004087 cornea Anatomy 0.000 claims description 15
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 claims description 14
- BTBUEUYNUDRHOZ-UHFFFAOYSA-N Borate Chemical group [O-]B([O-])[O-] BTBUEUYNUDRHOZ-UHFFFAOYSA-N 0.000 claims description 13
- 206010029113 Neovascularisation Diseases 0.000 claims description 13
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 12
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 12
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 9
- 150000003856 quaternary ammonium compounds Chemical class 0.000 claims description 9
- 229910000147 aluminium phosphate Inorganic materials 0.000 claims description 8
- 239000000872 buffer Substances 0.000 claims description 8
- 150000001875 compounds Chemical class 0.000 claims description 8
- 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 7
- 206010012689 Diabetic retinopathy Diseases 0.000 claims description 7
- 230000033115 angiogenesis Effects 0.000 claims description 7
- 125000000623 heterocyclic group Chemical group 0.000 claims description 7
- 239000004310 lactic acid Substances 0.000 claims description 7
- 235000014655 lactic acid Nutrition 0.000 claims description 7
- 229910052736 halogen Chemical group 0.000 claims description 6
- 150000002367 halogens Chemical group 0.000 claims description 6
- 125000001072 heteroaryl group Chemical group 0.000 claims description 6
- 125000005842 heteroatom Chemical group 0.000 claims description 6
- 238000000034 method Methods 0.000 claims description 6
- 125000001624 naphthyl group Chemical group 0.000 claims description 6
- 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 claims description 5
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 claims description 5
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 5
- 239000000600 sorbitol Substances 0.000 claims description 5
- 239000004094 surface-active agent Substances 0.000 claims description 5
- 208000002691 Choroiditis Diseases 0.000 claims description 4
- 208000003971 Posterior uveitis Diseases 0.000 claims description 4
- 206010038848 Retinal detachment Diseases 0.000 claims description 4
- 208000017442 Retinal disease Diseases 0.000 claims description 4
- 230000004264 retinal detachment Effects 0.000 claims description 4
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 3
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 3
- 206010048964 Carotid artery occlusion Diseases 0.000 claims description 3
- 208000003569 Central serous chorioretinopathy Diseases 0.000 claims description 3
- 208000033379 Chorioretinopathy Diseases 0.000 claims description 3
- 206010008790 Choroidal rupture Diseases 0.000 claims description 3
- 206010058202 Cystoid macular oedema Diseases 0.000 claims description 3
- 206010012688 Diabetic retinal oedema Diseases 0.000 claims description 3
- 208000019878 Eales disease Diseases 0.000 claims description 3
- 201000002563 Histoplasmosis Diseases 0.000 claims description 3
- 206010065630 Iris neovascularisation Diseases 0.000 claims description 3
- 208000001344 Macular Edema Diseases 0.000 claims description 3
- 201000010183 Papilledema Diseases 0.000 claims description 3
- 102000001253 Protein Kinase Human genes 0.000 claims description 3
- 102000004022 Protein-Tyrosine Kinases Human genes 0.000 claims description 3
- 108090000412 Protein-Tyrosine Kinases Proteins 0.000 claims description 3
- 208000007135 Retinal Neovascularization Diseases 0.000 claims description 3
- 201000007527 Retinal artery occlusion Diseases 0.000 claims description 3
- 206010038886 Retinal oedema Diseases 0.000 claims description 3
- 201000000582 Retinoblastoma Diseases 0.000 claims description 3
- 206010038923 Retinopathy Diseases 0.000 claims description 3
- 206010038933 Retinopathy of prematurity Diseases 0.000 claims description 3
- 201000005485 Toxoplasmosis Diseases 0.000 claims description 3
- 208000001445 Uveomeningoencephalitic Syndrome Diseases 0.000 claims description 3
- 108091008605 VEGF receptors Proteins 0.000 claims description 3
- 102000009484 Vascular Endothelial Growth Factor Receptors Human genes 0.000 claims description 3
- 208000025749 Vogt-Koyanagi-Harada disease Diseases 0.000 claims description 3
- 239000004037 angiogenesis inhibitor Substances 0.000 claims description 3
- 125000004429 atom Chemical group 0.000 claims description 3
- 230000001684 chronic effect Effects 0.000 claims description 3
- 201000010206 cystoid macular edema Diseases 0.000 claims description 3
- 201000011190 diabetic macular edema Diseases 0.000 claims description 3
- 208000024519 eye neoplasm Diseases 0.000 claims description 3
- 125000005843 halogen group Chemical group 0.000 claims description 3
- 208000015181 infectious disease Diseases 0.000 claims description 3
- 230000002458 infectious effect Effects 0.000 claims description 3
- 230000002757 inflammatory effect Effects 0.000 claims description 3
- 230000000302 ischemic effect Effects 0.000 claims description 3
- 230000001404 mediated effect Effects 0.000 claims description 3
- 201000008106 ocular cancer Diseases 0.000 claims description 3
- 201000002575 ocular melanoma Diseases 0.000 claims description 3
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 3
- 201000007914 proliferative diabetic retinopathy Diseases 0.000 claims description 3
- 108060006633 protein kinase Proteins 0.000 claims description 3
- 201000011195 retinal edema Diseases 0.000 claims description 3
- 208000004644 retinal vein occlusion Diseases 0.000 claims description 3
- 201000008979 rubeosis iridis Diseases 0.000 claims description 3
- 201000000306 sarcoidosis Diseases 0.000 claims description 3
- 229920006395 saturated elastomer Polymers 0.000 claims description 3
- 125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 claims description 2
- 125000004739 (C1-C6) alkylsulfonyl group Chemical group 0.000 claims description 2
- 206010046851 Uveitis Diseases 0.000 claims description 2
- RUZLIIJDZBWWSA-INIZCTEOSA-N methyl 2-[[(1s)-1-(7-methyl-2-morpholin-4-yl-4-oxopyrido[1,2-a]pyrimidin-9-yl)ethyl]amino]benzoate Chemical group COC(=O)C1=CC=CC=C1N[C@@H](C)C1=CC(C)=CN2C(=O)C=C(N3CCOCC3)N=C12 RUZLIIJDZBWWSA-INIZCTEOSA-N 0.000 claims description 2
- 208000006379 syphilis Diseases 0.000 claims description 2
- 201000008827 tuberculosis Diseases 0.000 claims description 2
- 229910052760 oxygen Inorganic materials 0.000 claims 3
- 229910052717 sulfur Inorganic materials 0.000 claims 3
- YPWZFSMZSNIVAQ-UHWSPLBMSA-N (1S,3R,5R,6S,8R,10R,11S,13R,15R,16S,18R,20R,21S,23R,25R,26S,28R,30R,31S,33R,35R,36S,38R,40R,41R,42R,43R,44R,45R,46R,47R,48R,49R,50R,51R,52R,53R,54R,55R,56R)-5,15,40-tris(hydroxymethyl)-10,20,25,30,35-pentakis(2-hydroxypropoxymethyl)-2,4,7,9,12,14,17,19,22,24,27,29,32,34,37,39-hexadecaoxanonacyclo[36.2.2.23,6.28,11.213,16.218,21.223,26.228,31.233,36]hexapentacontane-41,42,43,44,45,46,47,48,49,50,51,52,53,54,55,56-hexadecol Chemical compound CC(O)COC[C@H]1O[C@@H]2O[C@@H]3[C@@H](CO)O[C@H](O[C@@H]4[C@@H](CO)O[C@H](O[C@@H]5[C@@H](COCC(C)O)O[C@H](O[C@@H]6[C@@H](COCC(C)O)O[C@H](O[C@@H]7[C@@H](COCC(C)O)O[C@H](O[C@@H]8[C@@H](COCC(C)O)O[C@H](O[C@@H]9[C@@H](CO)O[C@H](O[C@H]1[C@H](O)[C@H]2O)[C@H](O)[C@H]9O)[C@H](O)[C@H]8O)[C@H](O)[C@H]7O)[C@H](O)[C@H]6O)[C@H](O)[C@H]5O)[C@H](O)[C@H]4O)[C@H](O)[C@H]3O YPWZFSMZSNIVAQ-UHWSPLBMSA-N 0.000 claims 1
- 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
- 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
- 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 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
- 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 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
- FDQRHYXJUXHREN-UHFFFAOYSA-N 5-(6,7,8,9-tetrahydro-5h-pyrimido[4,5-c]azepin-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=5CCCNCC=5N=CN=4)C=C3C=C2)=NOC=1C1(C(F)(F)F)CC1 FDQRHYXJUXHREN-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
- 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 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
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- ZGSCGZBABSAMCI-ZDUSSCGKSA-N N-[1-ethyl-5-(trifluoromethyl)pyrazol-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 CCn1nc(NC(=O)n2ccc3c(C)c(Oc4ncnc5CN[C@@H](C)Cc45)ccc23)cc1C(F)(F)F ZGSCGZBABSAMCI-ZDUSSCGKSA-N 0.000 claims 1
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- WHGYBXFWUBPSRW-FOUAGVGXSA-N beta-cyclodextrin Chemical class OC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)CO)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1CO WHGYBXFWUBPSRW-FOUAGVGXSA-N 0.000 claims 1
- HFWBAJUCGJLYRY-HNNXBMFYSA-N ethyl (6s)-4-[1-[(5-cyclopropyl-1,2-oxazol-3-yl)carbamoyl]-4-methylindol-5-yl]oxy-6-methyl-6,8-dihydro-5h-pyrido[3,4-d]pyrimidine-7-carboxylate Chemical compound CCOC(=O)N([C@H](CC1=2)C)CC1=NC=NC=2OC(C(=C1C=C2)C)=CC=C1N2C(=O)NC(=NO1)C=C1C1CC1 HFWBAJUCGJLYRY-HNNXBMFYSA-N 0.000 claims 1
- ZLCRLQDKXHLOEE-HNNXBMFYSA-N ethyl (6s)-4-[1-[(5-cyclopropyl-1,2-oxazol-3-yl)carbamoyl]indol-5-yl]oxy-6-methyl-6,8-dihydro-5h-pyrido[3,4-d]pyrimidine-7-carboxylate Chemical compound CCOC(=O)N([C@H](CC1=2)C)CC1=NC=NC=2OC(C=C1C=C2)=CC=C1N2C(=O)NC(=NO1)C=C1C1CC1 ZLCRLQDKXHLOEE-HNNXBMFYSA-N 0.000 claims 1
- GDSRMADSINPKSL-HSEONFRVSA-N gamma-cyclodextrin Chemical class OC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)CO)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1CO GDSRMADSINPKSL-HSEONFRVSA-N 0.000 claims 1
- VELQYRQHUVNKJJ-UHFFFAOYSA-N n-(1-ethyl-5-methylpyrazol-3-yl)-5-[6-(methylaminomethyl)pyrimidin-4-yl]oxyindole-1-carboxamide Chemical compound C1=C(C)N(CC)N=C1NC(=O)N1C2=CC=C(OC=3N=CN=C(CNC)C=3)C=C2C=C1 VELQYRQHUVNKJJ-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
- PYUWZTQHQNKHIG-UHFFFAOYSA-N n-(4,4-dimethyl-5,6-dihydropyrrolo[1,2-b]pyrazol-2-yl)-5-(6,7,8,9-tetrahydro-5h-pyrimido[4,5-c]azepin-4-yloxy)indole-1-carboxamide Chemical compound C1NCCCC2=C1N=CN=C2OC(C=C1C=C2)=CC=C1N2C(=O)NC1=NN2CCC(C)(C)C2=C1 PYUWZTQHQNKHIG-UHFFFAOYSA-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
- 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
- HCIOKVDTHMBZIJ-UHFFFAOYSA-N n-(5-tert-butyl-1,2-oxazol-3-yl)-5-(6,7,8,9-tetrahydro-5h-pyrimido[4,5-c]azepin-4-yloxy)indole-1-carboxamide Chemical compound O1C(C(C)(C)C)=CC(NC(=O)N2C3=CC=C(OC=4C=5CCCNCC=5N=CN=4)C=C3C=C2)=N1 HCIOKVDTHMBZIJ-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
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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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- 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
- C07D487/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- 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
- C07D495/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D495/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- 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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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Inorganic Chemistry (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Molecular Biology (AREA)
- Ophthalmology & Optometry (AREA)
- Biochemistry (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Dispersion Chemistry (AREA)
- Vascular Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Medicinal Preparation (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201361831834P | 2013-06-06 | 2013-06-06 | |
| US61/831,834 | 2013-06-06 | ||
| US14/292,082 | 2014-05-30 | ||
| 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 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2897949A1 true CA2897949A1 (en) | 2014-12-11 |
Family
ID=52005966
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2897949A Abandoned CA2897949A1 (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 |
Country Status (15)
| Country | Link |
|---|---|
| US (1) | US10174006B2 (enExample) |
| EP (1) | EP3003270A1 (enExample) |
| JP (1) | JP6522592B2 (enExample) |
| KR (1) | KR20160015192A (enExample) |
| CN (1) | CN105188663A (enExample) |
| AR (1) | AR096473A1 (enExample) |
| AU (1) | AU2014274955B2 (enExample) |
| BR (1) | BR112015019744A8 (enExample) |
| CA (1) | CA2897949A1 (enExample) |
| CL (1) | CL2015003460A1 (enExample) |
| HK (1) | HK1221160A1 (enExample) |
| MX (1) | MX2015014091A (enExample) |
| PH (1) | PH12015501555A1 (enExample) |
| RU (1) | RU2015155604A (enExample) |
| WO (1) | WO2014197584A1 (enExample) |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| 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 |
Family Cites Families (20)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| 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 |
-
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
Also Published As
| Publication number | Publication date |
|---|---|
| CN105188663A (zh) | 2015-12-23 |
| AU2014274955A1 (en) | 2015-07-16 |
| JP6522592B2 (ja) | 2019-05-29 |
| HK1221160A1 (zh) | 2017-05-26 |
| JP2016521706A (ja) | 2016-07-25 |
| PH12015501555A1 (en) | 2015-09-21 |
| RU2015155604A3 (enExample) | 2018-05-28 |
| MX2015014091A (es) | 2015-12-15 |
| AR096473A1 (es) | 2015-12-30 |
| AU2014274955B2 (en) | 2019-02-21 |
| BR112015019744A2 (pt) | 2017-07-18 |
| US20140364392A1 (en) | 2014-12-11 |
| KR20160015192A (ko) | 2016-02-12 |
| BR112015019744A8 (pt) | 2019-11-05 |
| EP3003270A1 (en) | 2016-04-13 |
| US10174006B2 (en) | 2019-01-08 |
| CL2015003460A1 (es) | 2016-07-08 |
| RU2015155604A (ru) | 2017-07-17 |
| WO2014197584A1 (en) | 2014-12-11 |
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| Date | Code | Title | Description |
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Effective date: 20200831 |