CA2048245C - Treatment of cataract with prostacyclin compounds - Google Patents
Treatment of cataract with prostacyclin compounds Download PDFInfo
- Publication number
- CA2048245C CA2048245C CA002048245A CA2048245A CA2048245C CA 2048245 C CA2048245 C CA 2048245C CA 002048245 A CA002048245 A CA 002048245A CA 2048245 A CA2048245 A CA 2048245A CA 2048245 C CA2048245 C CA 2048245C
- Authority
- CA
- Canada
- Prior art keywords
- fluoro
- keto
- ester
- cataract
- ene
- 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.)
- Expired - Fee Related
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- 208000002177 Cataract Diseases 0.000 title claims abstract description 28
- 238000011282 treatment Methods 0.000 title claims abstract description 15
- 150000003815 prostacyclins Chemical class 0.000 title description 8
- -1 prostacyclin compound Chemical class 0.000 claims abstract description 53
- 229960001123 epoprostenol Drugs 0.000 claims abstract description 17
- 239000003085 diluting agent Substances 0.000 claims abstract description 8
- 239000003937 drug carrier Substances 0.000 claims abstract description 3
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 3
- 239000000546 pharmaceutical excipient Substances 0.000 claims abstract description 3
- 239000000203 mixture Substances 0.000 claims description 63
- 150000001875 compounds Chemical class 0.000 claims description 45
- 150000004702 methyl esters Chemical class 0.000 claims description 33
- 239000003814 drug Substances 0.000 claims description 4
- XZFRIPGNUQRGPI-WBQKLGIQSA-N Carbaprostacyclin Chemical compound C1\C(=C/CCCC(O)=O)C[C@@H]2[C@@H](/C=C/[C@@H](O)CCCCC)[C@H](O)C[C@@H]21 XZFRIPGNUQRGPI-WBQKLGIQSA-N 0.000 claims description 3
- 150000003180 prostaglandins Chemical class 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims description 2
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 72
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 69
- 125000000217 alkyl group Chemical group 0.000 description 34
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 33
- 238000005160 1H NMR spectroscopy Methods 0.000 description 27
- 101150041968 CDC13 gene Proteins 0.000 description 27
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 27
- 230000015572 biosynthetic process Effects 0.000 description 27
- 238000003786 synthesis reaction Methods 0.000 description 27
- 239000000047 product Substances 0.000 description 25
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 24
- 239000000243 solution Substances 0.000 description 24
- 239000012043 crude product Substances 0.000 description 23
- 125000001424 substituent group Chemical group 0.000 description 21
- 238000004440 column chromatography Methods 0.000 description 18
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 18
- 229910052799 carbon Inorganic materials 0.000 description 17
- 238000002360 preparation method Methods 0.000 description 17
- 239000011541 reaction mixture Substances 0.000 description 17
- 125000004432 carbon atom Chemical group C* 0.000 description 16
- 125000005843 halogen group Chemical group 0.000 description 16
- 238000010626 work up procedure Methods 0.000 description 16
- 230000002829 reductive effect Effects 0.000 description 15
- WYURNTSHIVDZCO-UHFFFAOYSA-N tetrahydrofuran Substances C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 15
- 150000002148 esters Chemical class 0.000 description 13
- 238000000034 method Methods 0.000 description 13
- 238000012360 testing method Methods 0.000 description 13
- GBLRQXKSCRCLBZ-AJSYEDJNSA-N (1S,2R,1'S,2'R)-doxacurium Chemical compound COC1=C(OC)C(OC)=CC(C[C@@H]2[N@@+](CCC3=C2C(=C(OC)C(OC)=C3)OC)(C)CCCOC(=O)CCC(=O)OCCC[N@+]2(C)[C@H](C3=C(OC)C(OC)=C(OC)C=C3CC2)CC=2C=C(OC)C(OC)=C(OC)C=2)=C1 GBLRQXKSCRCLBZ-AJSYEDJNSA-N 0.000 description 12
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 12
- 150000001721 carbon Chemical group 0.000 description 12
- RDKBPKDVUKIILQ-PWNJXKKXSA-N methyl 5-[(3aS,5R,6S,6aS)-6-[(E)-4-fluoro-3-oxooct-1-enyl]-5-(oxan-2-yloxy)-1,3a,4,5,6,6a-hexahydropentalen-2-yl]pent-4-enoate Chemical compound COC(=O)CCC=CC1=C[C@H]2C[C@H]([C@H]([C@H]2C1)\C=C\C(C(CCCC)F)=O)OC1OCCCC1 RDKBPKDVUKIILQ-PWNJXKKXSA-N 0.000 description 12
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 12
- ILPBINAXDRFYPL-UHFFFAOYSA-N 2-octene Chemical compound CCCCCC=CC ILPBINAXDRFYPL-UHFFFAOYSA-N 0.000 description 10
- 150000001299 aldehydes Chemical class 0.000 description 10
- TVMXDCGIABBOFY-UHFFFAOYSA-N octane Chemical compound CCCCCCCC TVMXDCGIABBOFY-UHFFFAOYSA-N 0.000 description 10
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 9
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 9
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 9
- 239000002253 acid Substances 0.000 description 9
- 235000019441 ethanol Nutrition 0.000 description 9
- 150000003839 salts Chemical class 0.000 description 9
- 125000003545 alkoxy group Chemical group 0.000 description 8
- 150000001450 anions Chemical class 0.000 description 8
- 125000003118 aryl group Chemical group 0.000 description 8
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 8
- 238000009472 formulation Methods 0.000 description 8
- 239000001257 hydrogen Substances 0.000 description 8
- 229910052739 hydrogen Inorganic materials 0.000 description 8
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 8
- KAQKFAOMNZTLHT-OZUDYXHBSA-N prostaglandin I2 Chemical class O1\C(=C/CCCC(O)=O)C[C@@H]2[C@@H](/C=C/[C@@H](O)CCCCC)[C@H](O)C[C@@H]21 KAQKFAOMNZTLHT-OZUDYXHBSA-N 0.000 description 8
- 239000000741 silica gel Substances 0.000 description 8
- 229910002027 silica gel Inorganic materials 0.000 description 8
- FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 8
- 229920000858 Cyclodextrin Polymers 0.000 description 7
- QPJVMBTYPHYUOC-UHFFFAOYSA-N Methyl benzoate Natural products COC(=O)C1=CC=CC=C1 QPJVMBTYPHYUOC-UHFFFAOYSA-N 0.000 description 7
- 239000002775 capsule Substances 0.000 description 7
- 229940097362 cyclodextrins Drugs 0.000 description 7
- 229910052731 fluorine Inorganic materials 0.000 description 7
- ABVPVQWGHKJSLZ-BVKCNIQUSA-N methyl 5-[(3as,5r,6s,6as)-6-(hydroxymethyl)-5-(oxan-2-yloxy)-1,3a,4,5,6,6a-hexahydropentalen-2-yl]pent-4-enoate Chemical compound O([C@@H]1C[C@@H]2C=C(C[C@@H]2[C@H]1CO)C=CCCC(=O)OC)C1CCCCO1 ABVPVQWGHKJSLZ-BVKCNIQUSA-N 0.000 description 7
- 230000003647 oxidation Effects 0.000 description 7
- 238000007254 oxidation reaction Methods 0.000 description 7
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 6
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 6
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 6
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
- KEHFJHPSOFFXBO-UHFFFAOYSA-N bicyclo[3.3.0]oct-2-ene Chemical compound C1C=CC2CCCC21 KEHFJHPSOFFXBO-UHFFFAOYSA-N 0.000 description 6
- 229910052801 chlorine Inorganic materials 0.000 description 6
- 201000010099 disease Diseases 0.000 description 6
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 6
- 230000000694 effects Effects 0.000 description 6
- 125000001153 fluoro group Chemical group F* 0.000 description 6
- GUVHJVVFYXOZTO-UFTNONRUSA-N methyl 5-[(3aS,5R,6S,6aS)-6-[[tert-butyl(dimethyl)silyl]oxymethyl]-5-(oxan-2-yloxy)-1,3a,4,5,6,6a-hexahydropentalen-2-yl]pent-4-enoate Chemical compound O([Si](C)(C)C(C)(C)C)C[C@@H]1[C@H]2CC(=C[C@H]2C[C@H]1OC1OCCCC1)C=CCCC(=O)OC GUVHJVVFYXOZTO-UFTNONRUSA-N 0.000 description 6
- 229910052757 nitrogen Inorganic materials 0.000 description 6
- 239000000843 powder Substances 0.000 description 6
- 229920006395 saturated elastomer Polymers 0.000 description 6
- 239000012312 sodium hydride Substances 0.000 description 6
- 229910000104 sodium hydride Inorganic materials 0.000 description 6
- MGRKRYZSJJKYRK-DESJMCAESA-N (5e)-5-[(3as,4r,5r,6as)-4-(4-fluoro-3-hydroxyoctyl)-5-(oxan-2-yloxy)-3,3a,4,5,6,6a-hexahydro-1h-pentalen-2-ylidene]pentanoic acid Chemical compound O([C@H]1[C@@H]([C@H]2CC(/C[C@H]2C1)=C/CCCC(O)=O)CCC(O)C(F)CCCC)C1CCCCO1 MGRKRYZSJJKYRK-DESJMCAESA-N 0.000 description 5
- SATLDHJDQKIISS-UVEJQENXSA-N O([C@H]1[C@H]([C@H]2CC(/C[C@H]2C1)=C/CCCC(O)=O)/C=C/C(=O)C(F)(F)CCCC)C1CCCCO1 Chemical compound O([C@H]1[C@H]([C@H]2CC(/C[C@H]2C1)=C/CCCC(O)=O)/C=C/C(=O)C(F)(F)CCCC)C1CCCCO1 SATLDHJDQKIISS-UVEJQENXSA-N 0.000 description 5
- 239000012298 atmosphere Substances 0.000 description 5
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 5
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 5
- 125000001309 chloro group Chemical group Cl* 0.000 description 5
- 210000000695 crystalline len Anatomy 0.000 description 5
- 125000004043 oxo group Chemical group O=* 0.000 description 5
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 5
- 239000002504 physiological saline solution Substances 0.000 description 5
- 239000012279 sodium borohydride Substances 0.000 description 5
- 229910000033 sodium borohydride Inorganic materials 0.000 description 5
- 125000001412 tetrahydropyranyl group Chemical group 0.000 description 5
- YCIKTZCPIPLQKP-NSAFYHSYSA-N (5e)-5-[(3as,4s,5r,6as)-4-[(e)-4,4-difluoro-3-hydroxyoct-1-enyl]-5-(oxan-2-yloxy)-3,3a,4,5,6,6a-hexahydro-1h-pentalen-2-ylidene]pentanoic acid Chemical compound O([C@H]1[C@H]([C@H]2CC(/C[C@H]2C1)=C/CCCC(O)=O)/C=C/C(O)C(F)(F)CCCC)C1CCCCO1 YCIKTZCPIPLQKP-NSAFYHSYSA-N 0.000 description 4
- 0 **(C[C@]([C@](C1)C(C2)C=C1C=O)[C@@]2OC1OCCCC1)=C Chemical compound **(C[C@]([C@](C1)C(C2)C=C1C=O)[C@@]2OC1OCCCC1)=C 0.000 description 4
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 4
- 101000862089 Clarkia lewisii Glucose-6-phosphate isomerase, cytosolic 1A Proteins 0.000 description 4
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 4
- 241001465754 Metazoa Species 0.000 description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
- 239000007864 aqueous solution Substances 0.000 description 4
- 125000004104 aryloxy group Chemical group 0.000 description 4
- 239000000460 chlorine Substances 0.000 description 4
- 239000000706 filtrate Substances 0.000 description 4
- 239000011737 fluorine Substances 0.000 description 4
- 229920000159 gelatin Polymers 0.000 description 4
- 235000019322 gelatine Nutrition 0.000 description 4
- 239000004615 ingredient Substances 0.000 description 4
- 238000002347 injection Methods 0.000 description 4
- 239000007924 injection Substances 0.000 description 4
- XJCBDXWZUZJIMR-CUOVIZPJSA-N methyl (5e)-5-[(3as,4s,5r,6as)-4-[(e)-4,4-difluoro-3-hydroxyoct-1-enyl]-5-(oxan-2-yloxy)-3,3a,4,5,6,6a-hexahydro-1h-pentalen-2-ylidene]pentanoate Chemical compound O([C@H]1[C@H]([C@H]2CC(/C[C@H]2C1)=C/CCCC(=O)OC)/C=C/C(O)C(F)(F)CCCC)C1CCCCO1 XJCBDXWZUZJIMR-CUOVIZPJSA-N 0.000 description 4
- XLXWXZUMAJQWHE-PGQBBXDDSA-N methyl 5-[(3as,5r,6s,6as)-6-[(e)-4,4-difluoro-3-oxooct-1-enyl]-5-(oxan-2-yloxy)-1,3a,4,5,6,6a-hexahydropentalen-2-yl]pentanoate Chemical compound O([C@H]1[C@H]([C@H]2CC(CCCCC(=O)OC)=C[C@H]2C1)/C=C/C(=O)C(F)(F)CCCC)C1CCCCO1 XLXWXZUMAJQWHE-PGQBBXDDSA-N 0.000 description 4
- 229940095102 methyl benzoate Drugs 0.000 description 4
- 125000004433 nitrogen atom Chemical group N* 0.000 description 4
- 229910052760 oxygen Inorganic materials 0.000 description 4
- SQGYOTSLMSWVJD-UHFFFAOYSA-N silver(1+) nitrate Chemical compound [Ag+].[O-]N(=O)=O SQGYOTSLMSWVJD-UHFFFAOYSA-N 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- 229910052717 sulfur Inorganic materials 0.000 description 4
- AKEJUJNQAAGONA-UHFFFAOYSA-N sulfur trioxide Chemical compound O=S(=O)=O AKEJUJNQAAGONA-UHFFFAOYSA-N 0.000 description 4
- 239000000725 suspension Substances 0.000 description 4
- CISDEVRDMKWPCP-UHFFFAOYSA-N 1-dimethoxyphosphoryl-3,3-difluoroheptan-2-one Chemical compound CCCCC(F)(F)C(=O)CP(=O)(OC)OC CISDEVRDMKWPCP-UHFFFAOYSA-N 0.000 description 3
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 3
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- 102100031132 Glucose-6-phosphate isomerase Human genes 0.000 description 3
- 241000282414 Homo sapiens Species 0.000 description 3
- 238000006809 Jones oxidation reaction Methods 0.000 description 3
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 3
- 125000004423 acyloxy group Chemical group 0.000 description 3
- 239000000654 additive Substances 0.000 description 3
- 150000001298 alcohols Chemical class 0.000 description 3
- 150000001338 aliphatic hydrocarbons Chemical group 0.000 description 3
- 125000005907 alkyl ester group Chemical group 0.000 description 3
- 125000004429 atom Chemical group 0.000 description 3
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 3
- 229940125904 compound 1 Drugs 0.000 description 3
- 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 description 3
- 239000012153 distilled water Substances 0.000 description 3
- 229910052736 halogen Inorganic materials 0.000 description 3
- 230000007062 hydrolysis Effects 0.000 description 3
- 238000006460 hydrolysis reaction Methods 0.000 description 3
- 230000002401 inhibitory effect Effects 0.000 description 3
- 239000008101 lactose Substances 0.000 description 3
- GMSIJUKBLIQKMI-LUMPXTQCSA-N methyl (5e)-5-[(3as,4r,5r,6as)-4-(4-fluoro-3-hydroxyoctyl)-5-(oxan-2-yloxy)-3,3a,4,5,6,6a-hexahydro-1h-pentalen-2-ylidene]pentanoate Chemical compound O([C@H]1[C@@H]([C@H]2CC(/C[C@H]2C1)=C/CCCC(=O)OC)CCC(O)C(F)CCCC)C1CCCCO1 GMSIJUKBLIQKMI-LUMPXTQCSA-N 0.000 description 3
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 3
- 229940054534 ophthalmic solution Drugs 0.000 description 3
- 239000002997 ophthalmic solution Substances 0.000 description 3
- 239000001301 oxygen Substances 0.000 description 3
- WGJJROVFWIXTPA-OALUTQOASA-N prostanoic acid Chemical compound CCCCCCCC[C@H]1CCC[C@@H]1CCCCCCC(O)=O WGJJROVFWIXTPA-OALUTQOASA-N 0.000 description 3
- 238000007363 ring formation reaction Methods 0.000 description 3
- 239000011593 sulfur Substances 0.000 description 3
- LOFJKBAHPJENQS-UHFFFAOYSA-N tris(oxomethylidene)chromium Chemical compound O=C=[Cr](=C=O)=C=O LOFJKBAHPJENQS-UHFFFAOYSA-N 0.000 description 3
- OYGZAHLDOIYQRO-DUEJJRPTSA-N (5E)-5-[(3aS,4S,5R,6aS)-4-[(E)-4-fluoro-3-oxooct-1-enyl]-5-(oxan-2-yloxy)-3,3a,4,5,6,6a-hexahydro-1H-pentalen-2-ylidene]pentanoic acid Chemical compound O([C@H]1[C@H]([C@H]2CC(/C[C@H]2C1)=C/CCCC(O)=O)/C=C/C(=O)C(F)CCCC)C1CCCCO1 OYGZAHLDOIYQRO-DUEJJRPTSA-N 0.000 description 2
- NHLQCQLQOLYBGR-VOKAQTQYSA-N (5e)-5-[(3as,4s,5r,6as)-4-[(e)-4-fluoro-3-hydroxyoct-1-enyl]-5-(oxan-2-yloxy)-3,3a,4,5,6,6a-hexahydro-1h-pentalen-2-ylidene]pentanoic acid Chemical compound O([C@H]1[C@H]([C@H]2CC(/C[C@H]2C1)=C/CCCC(O)=O)/C=C/C(O)C(F)CCCC)C1CCCCO1 NHLQCQLQOLYBGR-VOKAQTQYSA-N 0.000 description 2
- NKVJKVMGJABKHV-UHFFFAOYSA-N 3-carboxypropyl(triphenyl)phosphanium;bromide Chemical compound [Br-].C=1C=CC=CC=1[P+](C=1C=CC=CC=1)(CCCC(=O)O)C1=CC=CC=C1 NKVJKVMGJABKHV-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 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 description 2
- YXHKONLOYHBTNS-UHFFFAOYSA-N Diazomethane Chemical compound C=[N+]=[N-] YXHKONLOYHBTNS-UHFFFAOYSA-N 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- 108010010803 Gelatin Proteins 0.000 description 2
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- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 2
- 229930195725 Mannitol Natural products 0.000 description 2
- ABLZXFCXXLZCGV-UHFFFAOYSA-N Phosphorous acid Chemical class OP(O)=O ABLZXFCXXLZCGV-UHFFFAOYSA-N 0.000 description 2
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- 125000003710 aryl alkyl group Chemical group 0.000 description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
- 239000002585 base Substances 0.000 description 2
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 2
- 229940125782 compound 2 Drugs 0.000 description 2
- 229940126214 compound 3 Drugs 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
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- 239000003885 eye ointment Substances 0.000 description 2
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- 235000011852 gelatine desserts Nutrition 0.000 description 2
- 150000002373 hemiacetals Chemical class 0.000 description 2
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 2
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 2
- 229940102223 injectable solution Drugs 0.000 description 2
- 150000002576 ketones Chemical class 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 239000000594 mannitol Substances 0.000 description 2
- 235000010355 mannitol Nutrition 0.000 description 2
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- HYVDLTARHGBGCA-CZIWLORCSA-N methyl 5-[(3aS,5R,6S,6aS)-6-[(E)-4,4-difluoro-3-hydroxyoct-1-enyl]-5-(oxan-2-yloxy)-1,3a,4,5,6,6a-hexahydropentalen-2-yl]pent-4-enoate Chemical compound COC(=O)CCC=CC1=C[C@H]2C[C@H]([C@H]([C@H]2C1)\C=C\C(C(CCCC)(F)F)O)OC1OCCCC1 HYVDLTARHGBGCA-CZIWLORCSA-N 0.000 description 2
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- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
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Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/557—Eicosanoids, e.g. leukotrienes or prostaglandins
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
- A61P27/12—Ophthalmic agents for cataracts
Landscapes
- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Epidemiology (AREA)
- Ophthalmology & Optometry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP20645090 | 1990-08-02 | ||
| JP206450/1990 | 1990-08-02 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2048245A1 CA2048245A1 (en) | 1992-02-03 |
| CA2048245C true CA2048245C (en) | 2003-01-07 |
Family
ID=16523576
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002048245A Expired - Fee Related CA2048245C (en) | 1990-08-02 | 1991-07-31 | Treatment of cataract with prostacyclin compounds |
Country Status (11)
| Country | Link |
|---|---|
| US (1) | US5162370A (en, 2012) |
| EP (1) | EP0469782B1 (en, 2012) |
| JP (1) | JPH07100656B2 (en, 2012) |
| KR (1) | KR0157991B1 (en, 2012) |
| AT (1) | ATE146964T1 (en, 2012) |
| CA (1) | CA2048245C (en, 2012) |
| DE (1) | DE69123892T2 (en, 2012) |
| DK (1) | DK0469782T3 (en, 2012) |
| ES (1) | ES2098325T3 (en, 2012) |
| GR (1) | GR3022217T3 (en, 2012) |
| TW (1) | TW205508B (en, 2012) |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| TW224942B (en, 2012) * | 1990-04-04 | 1994-06-11 | Adka Ueno Kk | |
| TW205508B (en, 2012) * | 1990-08-02 | 1993-05-11 | Kabushikaisha Ueno Seiyaku Oyo Kenkyujo | |
| SE9303627D0 (sv) * | 1993-11-03 | 1993-11-03 | Kabi Pharmacia Ab | Method and means for prevention of cataract |
| WO1997041864A1 (fr) * | 1996-05-07 | 1997-11-13 | Kaken Pharmaceutical Co., Ltd. | Preparations ophtalmiques |
| CN111511402A (zh) * | 2017-12-28 | 2020-08-07 | 国立大学法人福井大学 | 白内障的预防剂及/或治疗剂、用于预防及/或治疗白内障的医药组合物、ppar活化剂的用于制造它们的用途、以及滴眼剂 |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE2912409A1 (de) * | 1978-03-31 | 1979-10-11 | Ono Pharmaceutical Co | 6,9-methano-pgi tief 2 -analoge |
| EP0134153B1 (en) * | 1983-08-19 | 1989-04-19 | Sagami Chemical Research Center | Bicyclo[3.3.0]octane derivative and preparation thereof |
| JPS62234085A (ja) * | 1985-12-18 | 1987-10-14 | Sankyo Co Ltd | チアゾリジン誘導体を有効成分とする糖尿病性合併症治療剤 |
| TW224942B (en, 2012) * | 1990-04-04 | 1994-06-11 | Adka Ueno Kk | |
| TW205508B (en, 2012) * | 1990-08-02 | 1993-05-11 | Kabushikaisha Ueno Seiyaku Oyo Kenkyujo |
-
1991
- 1991-07-23 TW TW080105691A patent/TW205508B/zh active
- 1991-07-24 EP EP91306768A patent/EP0469782B1/en not_active Expired - Lifetime
- 1991-07-24 DE DE69123892T patent/DE69123892T2/de not_active Expired - Fee Related
- 1991-07-24 DK DK91306768.2T patent/DK0469782T3/da active
- 1991-07-24 ES ES91306768T patent/ES2098325T3/es not_active Expired - Lifetime
- 1991-07-24 AT AT91306768T patent/ATE146964T1/de not_active IP Right Cessation
- 1991-07-31 CA CA002048245A patent/CA2048245C/en not_active Expired - Fee Related
- 1991-08-01 US US07/739,069 patent/US5162370A/en not_active Expired - Lifetime
- 1991-08-01 JP JP3192947A patent/JPH07100656B2/ja not_active Expired - Lifetime
- 1991-08-02 KR KR1019910013444A patent/KR0157991B1/ko not_active Expired - Fee Related
-
1997
- 1997-01-03 GR GR960403647T patent/GR3022217T3/el unknown
Also Published As
| Publication number | Publication date |
|---|---|
| EP0469782A2 (en) | 1992-02-05 |
| ES2098325T3 (es) | 1997-05-01 |
| US5162370A (en) | 1992-11-10 |
| GR3022217T3 (en) | 1997-04-30 |
| EP0469782A3 (en) | 1993-01-13 |
| KR0157991B1 (ko) | 1998-12-01 |
| EP0469782B1 (en) | 1997-01-02 |
| JPH054923A (ja) | 1993-01-14 |
| DE69123892D1 (de) | 1997-02-13 |
| ATE146964T1 (de) | 1997-01-15 |
| JPH07100656B2 (ja) | 1995-11-01 |
| CA2048245A1 (en) | 1992-02-03 |
| TW205508B (en, 2012) | 1993-05-11 |
| DK0469782T3 (da) | 1997-01-20 |
| KR920003972A (ko) | 1992-03-27 |
| DE69123892T2 (de) | 1997-04-30 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request | ||
| MKLA | Lapsed |