CA2039420C - Treatment of cataract with 15-keto-prostaglandin compounds - Google Patents
Treatment of cataract with 15-keto-prostaglandin compoundsInfo
- Publication number
- CA2039420C CA2039420C CA002039420A CA2039420A CA2039420C CA 2039420 C CA2039420 C CA 2039420C CA 002039420 A CA002039420 A CA 002039420A CA 2039420 A CA2039420 A CA 2039420A CA 2039420 C CA2039420 C CA 2039420C
- Authority
- CA
- Canada
- Prior art keywords
- compound
- alkyl
- keto
- dihydro
- give
- 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 - Lifetime
Links
- 208000002177 Cataract Diseases 0.000 title claims abstract description 43
- 238000011282 treatment Methods 0.000 title claims abstract description 16
- 150000001875 compounds Chemical class 0.000 claims abstract description 249
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 71
- 125000005843 halogen group Chemical group 0.000 claims abstract description 31
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 19
- 150000003839 salts Chemical class 0.000 claims abstract description 12
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 10
- 239000003085 diluting agent Substances 0.000 claims abstract description 8
- 125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 5
- 125000002947 alkylene group Chemical group 0.000 claims abstract description 4
- 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
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims abstract 5
- 239000000203 mixture Substances 0.000 claims description 49
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 18
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 15
- 229910052731 fluorine Inorganic materials 0.000 claims description 14
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 13
- 125000004043 oxo group Chemical group O=* 0.000 claims description 10
- 125000003118 aryl group Chemical group 0.000 claims description 7
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 7
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 7
- 125000001153 fluoro group Chemical group F* 0.000 claims description 6
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 5
- XAKBSHICSHRJCL-UHFFFAOYSA-N [CH2]C(=O)C1=CC=CC=C1 Chemical group [CH2]C(=O)C1=CC=CC=C1 XAKBSHICSHRJCL-UHFFFAOYSA-N 0.000 claims description 4
- 239000003814 drug Substances 0.000 claims description 4
- 125000002950 monocyclic group Chemical group 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims description 2
- 238000002360 preparation method Methods 0.000 description 72
- 239000000243 solution Substances 0.000 description 68
- -1 -isopropyl ester Chemical class 0.000 description 65
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 60
- 238000012360 testing method Methods 0.000 description 59
- 239000011369 resultant mixture Substances 0.000 description 53
- 238000000034 method Methods 0.000 description 50
- 150000002148 esters Chemical class 0.000 description 39
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 32
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 30
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 30
- 125000004432 carbon atom Chemical group C* 0.000 description 29
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 25
- BKONIFYZHZUXLS-UHFFFAOYSA-N 6-carboxyhexylphosphanium;bromide Chemical compound [Br-].OC(=O)CCCCCC[PH3+] BKONIFYZHZUXLS-UHFFFAOYSA-N 0.000 description 23
- 238000010898 silica gel chromatography Methods 0.000 description 23
- 239000002504 physiological saline solution Substances 0.000 description 22
- GQHTUMJGOHRCHB-UHFFFAOYSA-N 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine Chemical compound C1CCCCN2CCCN=C21 GQHTUMJGOHRCHB-UHFFFAOYSA-N 0.000 description 21
- 239000012043 crude product Substances 0.000 description 19
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 18
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 18
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 17
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 15
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 15
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 15
- 229910052739 hydrogen Inorganic materials 0.000 description 15
- 230000000694 effects Effects 0.000 description 14
- 238000009472 formulation Methods 0.000 description 14
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 14
- 229910052799 carbon Inorganic materials 0.000 description 13
- 150000002576 ketones Chemical group 0.000 description 13
- HOJNQHKCNPGJGJ-YLIIVCRJSA-N phenacyl (z)-9-[(1r,2r,3r)-2-(4,4-difluoro-3-oxooctyl)-3-hydroxy-5-oxocyclopentyl]non-7-enoate Chemical compound CCCCC(F)(F)C(=O)CC[C@H]1[C@H](O)CC(=O)[C@@H]1C\C=C/CCCCCC(=O)OCC(=O)C1=CC=CC=C1 HOJNQHKCNPGJGJ-YLIIVCRJSA-N 0.000 description 13
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 12
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
- 239000002775 capsule Substances 0.000 description 12
- 125000006239 protecting group Chemical group 0.000 description 12
- 230000002829 reductive effect Effects 0.000 description 12
- 125000001424 substituent group Chemical group 0.000 description 12
- HUHXLHLWASNVDB-UHFFFAOYSA-N 2-(oxan-2-yloxy)oxane Chemical compound O1CCCCC1OC1OCCCC1 HUHXLHLWASNVDB-UHFFFAOYSA-N 0.000 description 11
- 210000000695 crystalline len Anatomy 0.000 description 11
- 239000000843 powder Substances 0.000 description 11
- 239000000047 product Substances 0.000 description 11
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 10
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 10
- 241001465754 Metazoa Species 0.000 description 10
- 150000001299 aldehydes Chemical class 0.000 description 10
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 10
- 239000001257 hydrogen Substances 0.000 description 10
- 229920006395 saturated elastomer Polymers 0.000 description 10
- 238000004440 column chromatography Methods 0.000 description 9
- 229920000858 Cyclodextrin Polymers 0.000 description 8
- 101000799461 Homo sapiens Thrombopoietin Proteins 0.000 description 8
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 8
- 241000700159 Rattus Species 0.000 description 8
- 102100034195 Thrombopoietin Human genes 0.000 description 8
- 229960000711 alprostadil Drugs 0.000 description 8
- 229940097362 cyclodextrins Drugs 0.000 description 8
- 229960002986 dinoprostone Drugs 0.000 description 8
- 229930182830 galactose Natural products 0.000 description 8
- 239000004615 ingredient Substances 0.000 description 8
- 150000004702 methyl esters Chemical class 0.000 description 8
- 229940073584 methylene chloride Drugs 0.000 description 8
- 239000012046 mixed solvent Substances 0.000 description 8
- 238000007920 subcutaneous administration Methods 0.000 description 8
- 239000000126 substance Substances 0.000 description 8
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 8
- 238000005160 1H NMR spectroscopy Methods 0.000 description 7
- SXXLKZCNJHJYFL-UHFFFAOYSA-N 4,5,6,7-tetrahydro-[1,2]oxazolo[4,5-c]pyridin-5-ium-3-olate Chemical compound C1CNCC2=C1ONC2=O SXXLKZCNJHJYFL-UHFFFAOYSA-N 0.000 description 7
- 241000700157 Rattus norvegicus Species 0.000 description 7
- 125000003545 alkoxy group Chemical group 0.000 description 7
- 239000012300 argon atmosphere Substances 0.000 description 7
- 235000005911 diet Nutrition 0.000 description 7
- 230000037213 diet Effects 0.000 description 7
- 235000019441 ethanol Nutrition 0.000 description 7
- 230000003203 everyday effect Effects 0.000 description 7
- 238000002347 injection Methods 0.000 description 7
- 239000007924 injection Substances 0.000 description 7
- IASRMNRQZIRYHM-UHFFFAOYSA-N 6-carboxyhexyl(triphenyl)phosphanium;bromide Chemical compound [Br-].C=1C=CC=CC=1[P+](C=1C=CC=CC=1)(CCCCCCC(=O)O)C1=CC=CC=C1 IASRMNRQZIRYHM-UHFFFAOYSA-N 0.000 description 6
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 6
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 6
- 238000006859 Swern oxidation reaction Methods 0.000 description 6
- 239000012298 atmosphere Substances 0.000 description 6
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 6
- 238000013461 design Methods 0.000 description 6
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 6
- 229920000159 gelatin Polymers 0.000 description 6
- 235000019322 gelatine Nutrition 0.000 description 6
- 230000002401 inhibitory effect Effects 0.000 description 6
- FBUKVWPVBMHYJY-UHFFFAOYSA-N nonanoic acid Chemical compound CCCCCCCCC(O)=O FBUKVWPVBMHYJY-UHFFFAOYSA-N 0.000 description 6
- NSCXBOBVIXPOPW-NWCIEGOKSA-N propan-2-yl (z)-9-[(1r,2r,3r,5s)-2-[2-(2-heptyl-1,3-dioxolan-2-yl)ethyl]-5-hydroxy-3-(oxan-2-yloxy)cyclopentyl]non-7-enoate Chemical compound C([C@@H]1[C@H]([C@@H](O)C[C@H]1OC1OCCCC1)C\C=C/CCCCCC(=O)OC(C)C)CC1(CCCCCCC)OCCO1 NSCXBOBVIXPOPW-NWCIEGOKSA-N 0.000 description 6
- QBEDUXZCSTWZTP-KCZVDYSFSA-N propan-2-yl 9-[(1r,2r,3r)-2-(4,4-difluoro-3-oxooctyl)-3-hydroxy-5-oxocyclopentyl]nonanoate Chemical compound CCCCC(F)(F)C(=O)CC[C@H]1[C@H](O)CC(=O)[C@@H]1CCCCCCCCC(=O)OC(C)C QBEDUXZCSTWZTP-KCZVDYSFSA-N 0.000 description 6
- FTCKOEKJNDVBJD-MUNZXYLSSA-N (3ar,4r,5r,6as)-4-(4,4-difluoro-5-oxooctyl)-5-(oxan-2-yloxy)-3,3a,4,5,6,6a-hexahydrocyclopenta[b]furan-2-one Chemical compound O([C@H]1[C@@H]([C@H]2CC(=O)O[C@H]2C1)CCCC(F)(F)C(=O)CCC)C1CCCCO1 FTCKOEKJNDVBJD-MUNZXYLSSA-N 0.000 description 5
- 101150041968 CDC13 gene Proteins 0.000 description 5
- 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 5
- 229930195725 Mannitol Natural products 0.000 description 5
- 238000005481 NMR spectroscopy Methods 0.000 description 5
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 5
- 238000001816 cooling Methods 0.000 description 5
- 201000010099 disease Diseases 0.000 description 5
- 239000012153 distilled water Substances 0.000 description 5
- 239000000706 filtrate Substances 0.000 description 5
- 239000000594 mannitol Substances 0.000 description 5
- 235000010355 mannitol Nutrition 0.000 description 5
- REPVRVIBFFXYLH-DKHJWVMHSA-N methyl (z)-9-[(1r,2r,3r,5s)-2-(4,4-difluoro-3-oxooctyl)-3,5-dihydroxycyclopentyl]non-7-enoate Chemical compound CCCCC(F)(F)C(=O)CC[C@H]1[C@H](O)C[C@H](O)[C@@H]1C\C=C/CCCCCC(=O)OC REPVRVIBFFXYLH-DKHJWVMHSA-N 0.000 description 5
- YRKODSCXNKWHGO-GHMGVUHVSA-N phenacyl (z)-9-[(1r,2r,3r)-2-(4,4-difluoro-3-oxooctyl)-3-(oxan-2-yloxy)-5-oxocyclopentyl]non-7-enoate Chemical compound C([C@H]1C(=O)C[C@H]([C@@H]1CCC(=O)C(F)(F)CCCC)OC1OCCCC1)\C=C/CCCCCC(=O)OCC(=O)C1=CC=CC=C1 YRKODSCXNKWHGO-GHMGVUHVSA-N 0.000 description 5
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 5
- 238000006722 reduction reaction Methods 0.000 description 5
- 229910000033 sodium borohydride Inorganic materials 0.000 description 5
- 239000012279 sodium borohydride Substances 0.000 description 5
- 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 4
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 4
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 4
- 239000001828 Gelatine Substances 0.000 description 4
- 238000006809 Jones oxidation reaction Methods 0.000 description 4
- 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 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
- WGLPBDUCMAPZCE-UHFFFAOYSA-N Trioxochromium Chemical compound O=[Cr](=O)=O WGLPBDUCMAPZCE-UHFFFAOYSA-N 0.000 description 4
- 239000004480 active ingredient Substances 0.000 description 4
- 125000005907 alkyl ester group Chemical group 0.000 description 4
- SIPUZPBQZHNSDW-UHFFFAOYSA-N bis(2-methylpropyl)aluminum Chemical compound CC(C)C[Al]CC(C)C SIPUZPBQZHNSDW-UHFFFAOYSA-N 0.000 description 4
- 230000003197 catalytic effect Effects 0.000 description 4
- 238000006243 chemical reaction Methods 0.000 description 4
- 239000003795 chemical substances by application Substances 0.000 description 4
- 239000000460 chlorine Substances 0.000 description 4
- 229910052801 chlorine Inorganic materials 0.000 description 4
- KPUWHANPEXNPJT-UHFFFAOYSA-N disiloxane Chemical compound [SiH3]O[SiH3] KPUWHANPEXNPJT-UHFFFAOYSA-N 0.000 description 4
- 239000011737 fluorine Substances 0.000 description 4
- 150000002367 halogens Chemical group 0.000 description 4
- 229940102223 injectable solution Drugs 0.000 description 4
- 239000008101 lactose Substances 0.000 description 4
- 230000003647 oxidation Effects 0.000 description 4
- 238000007254 oxidation reaction Methods 0.000 description 4
- NFUUAVFPTHMLHW-VOQKXKRBSA-N propan-2-yl (z)-9-[(1r,2r,3r,5s)-3,5-dihydroxy-2-(3-oxodecyl)cyclopentyl]non-7-enoate Chemical compound CCCCCCCC(=O)CC[C@H]1[C@H](O)C[C@H](O)[C@@H]1C\C=C/CCCCCC(=O)OC(C)C NFUUAVFPTHMLHW-VOQKXKRBSA-N 0.000 description 4
- 150000003180 prostaglandins Chemical class 0.000 description 4
- WGJJROVFWIXTPA-OALUTQOASA-N prostanoic acid Chemical compound CCCCCCCC[C@H]1CCC[C@@H]1CCCCCCC(O)=O WGJJROVFWIXTPA-OALUTQOASA-N 0.000 description 4
- RMAQACBXLXPBSY-UHFFFAOYSA-N silicic acid Chemical compound O[Si](O)(O)O RMAQACBXLXPBSY-UHFFFAOYSA-N 0.000 description 4
- 235000012239 silicon dioxide Nutrition 0.000 description 4
- 239000000725 suspension Substances 0.000 description 4
- UEJICTILJZKHQY-MUNZXYLSSA-N (3ar,4r,5r,6as)-4-(4,4-difluoro-3-oxooctyl)-5-(oxan-2-yloxy)-3,3a,4,5,6,6a-hexahydrocyclopenta[b]furan-2-one Chemical compound O([C@H]1[C@@H]([C@H]2CC(=O)O[C@H]2C1)CCC(=O)C(F)(F)CCCC)C1CCCCO1 UEJICTILJZKHQY-MUNZXYLSSA-N 0.000 description 3
- CORRAXPZMWTYIP-LPGFFSAWSA-N (3ar,4r,5r,6as)-4-(hydroxymethyl)-5-(oxan-2-yloxy)-3,3a,4,5,6,6a-hexahydrocyclopenta[b]furan-2-one Chemical compound O([C@H]1[C@H]([C@H]2CC(=O)O[C@H]2C1)CO)C1CCCCO1 CORRAXPZMWTYIP-LPGFFSAWSA-N 0.000 description 3
- BXSCNNADPQDDOK-HYPYWDQKSA-N (3ar,4r,5r,6as)-4-[(e)-4,4-difluoro-5-oxooct-2-enyl]-5-(oxan-2-yloxy)-3,3a,4,5,6,6a-hexahydrocyclopenta[b]furan-2-one Chemical compound O([C@H]1[C@@H]([C@H]2CC(=O)O[C@H]2C1)C/C=C/C(F)(F)C(=O)CCC)C1CCCCO1 BXSCNNADPQDDOK-HYPYWDQKSA-N 0.000 description 3
- JLPQXFFMVVPIRW-UHFFFAOYSA-N 7-bromoheptanoic acid Chemical compound OC(=O)CCCCCCBr JLPQXFFMVVPIRW-UHFFFAOYSA-N 0.000 description 3
- 241000282414 Homo sapiens Species 0.000 description 3
- 229920000954 Polyglycolide Polymers 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 3
- CZEBTZMIQZVUSE-UHFFFAOYSA-N [6-cyano-1-[(2-methylpropan-2-yl)oxycarbonyl]indol-2-yl]boronic acid Chemical compound C1=C(C#N)C=C2N(C(=O)OC(C)(C)C)C(B(O)O)=CC2=C1 CZEBTZMIQZVUSE-UHFFFAOYSA-N 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- 239000000654 additive Substances 0.000 description 3
- 150000001338 aliphatic hydrocarbons Chemical group 0.000 description 3
- 239000007864 aqueous solution Substances 0.000 description 3
- 125000004104 aryloxy group Chemical group 0.000 description 3
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 3
- 239000001913 cellulose Substances 0.000 description 3
- 229920002678 cellulose Polymers 0.000 description 3
- 125000001309 chloro group Chemical group Cl* 0.000 description 3
- 239000010949 copper Substances 0.000 description 3
- 238000010511 deprotection reaction Methods 0.000 description 3
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 3
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
- 150000002596 lactones Chemical group 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- 229940054534 ophthalmic solution Drugs 0.000 description 3
- 239000002997 ophthalmic solution Substances 0.000 description 3
- 229940094443 oxytocics prostaglandins Drugs 0.000 description 3
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 description 3
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 3
- 239000012312 sodium hydride Substances 0.000 description 3
- 229910000104 sodium hydride Inorganic materials 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- 125000001412 tetrahydropyranyl group Chemical group 0.000 description 3
- XTHLWLJWJINZOO-NKALFCTASA-N (3aR,4R,5R,6aS)-4-(3-tert-butyl-4,4-difluoro-8-methyl-8-silyloxynonyl)-5-(oxan-2-yloxy)-3,3a,4,5,6,6a-hexahydro-2H-cyclopenta[b]furan-2-ol Chemical compound C(C)(C)(C)C(CC[C@@H]1[C@H]2CC(O[C@H]2C[C@H]1OC1OCCCC1)O)C(CCCC(O[SiH3])(C)C)(F)F XTHLWLJWJINZOO-NKALFCTASA-N 0.000 description 2
- LEWMANYBGYSQMC-GMIZXNJASA-N (3aR,4R,5R,6aS)-4-hydroxy-6a-methyl-5-(oxan-2-yloxy)-3a,4,5,6-tetrahydro-3H-cyclopenta[b]furan-2-one Chemical compound O[C@@H]1[C@H]2CC(O[C@]2(C[C@H]1OC1OCCCC1)C)=O LEWMANYBGYSQMC-GMIZXNJASA-N 0.000 description 2
- GMVPRGQOIOIIMI-UHFFFAOYSA-N (8R,11R,12R,13E,15S)-11,15-Dihydroxy-9-oxo-13-prostenoic acid Natural products CCCCCC(O)C=CC1C(O)CC(=O)C1CCCCCCC(O)=O GMVPRGQOIOIIMI-UHFFFAOYSA-N 0.000 description 2
- 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 2
- RHLVCLIPMVJYKS-UHFFFAOYSA-N 3-octanone Chemical compound CCCCCC(=O)CC RHLVCLIPMVJYKS-UHFFFAOYSA-N 0.000 description 2
- MLOSJPZSZWUDSK-UHFFFAOYSA-N 4-carboxybutyl(triphenyl)phosphanium;bromide Chemical compound [Br-].C=1C=CC=CC=1[P+](C=1C=CC=CC=1)(CCCCC(=O)O)C1=CC=CC=C1 MLOSJPZSZWUDSK-UHFFFAOYSA-N 0.000 description 2
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 2
- 229910002012 Aerosil® Inorganic materials 0.000 description 2
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
- KZGNJLHBTZMSMD-UHFFFAOYSA-N C[Cu]C Chemical compound C[Cu]C KZGNJLHBTZMSMD-UHFFFAOYSA-N 0.000 description 2
- 239000012027 Collins reagent Substances 0.000 description 2
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 2
- BUDQDWGNQVEFAC-UHFFFAOYSA-N Dihydropyran Chemical compound C1COC=CC1 BUDQDWGNQVEFAC-UHFFFAOYSA-N 0.000 description 2
- 108010010803 Gelatin Proteins 0.000 description 2
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
- 101150020741 Hpgds gene Proteins 0.000 description 2
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 2
- 241000047703 Nonion Species 0.000 description 2
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 2
- 238000007239 Wittig reaction Methods 0.000 description 2
- 125000004423 acyloxy group Chemical group 0.000 description 2
- 150000001408 amides Chemical class 0.000 description 2
- 239000002585 base Substances 0.000 description 2
- AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 description 2
- 238000009903 catalytic hydrogenation reaction Methods 0.000 description 2
- 238000010531 catalytic reduction reaction Methods 0.000 description 2
- 238000004587 chromatography analysis Methods 0.000 description 2
- 229940125904 compound 1 Drugs 0.000 description 2
- 229940125898 compound 5 Drugs 0.000 description 2
- 229910052802 copper Inorganic materials 0.000 description 2
- 230000003247 decreasing effect Effects 0.000 description 2
- 239000000839 emulsion Substances 0.000 description 2
- 230000032050 esterification Effects 0.000 description 2
- 238000005886 esterification reaction Methods 0.000 description 2
- 239000003885 eye ointment Substances 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 239000008273 gelatin Substances 0.000 description 2
- 239000007903 gelatin capsule Substances 0.000 description 2
- 235000011852 gelatine desserts Nutrition 0.000 description 2
- 150000002373 hemiacetals Chemical class 0.000 description 2
- 150000002431 hydrogen Chemical class 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 239000011630 iodine Substances 0.000 description 2
- 229910052740 iodine Inorganic materials 0.000 description 2
- FMKOJHQHASLBPH-UHFFFAOYSA-N isopropyl iodide Chemical compound CC(C)I FMKOJHQHASLBPH-UHFFFAOYSA-N 0.000 description 2
- XXUPXHKCPIKWLR-JHUOEJJVSA-N isopropyl unoprostone Chemical group CCCCCCCC(=O)CC[C@H]1[C@H](O)C[C@H](O)[C@@H]1C\C=C/CCCC(=O)OC(C)C XXUPXHKCPIKWLR-JHUOEJJVSA-N 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
- 238000002156 mixing Methods 0.000 description 2
- 229940069265 ophthalmic ointment Drugs 0.000 description 2
- 230000001590 oxidative effect Effects 0.000 description 2
- 229910052760 oxygen Inorganic materials 0.000 description 2
- 150000003904 phospholipids Chemical class 0.000 description 2
- 239000006187 pill Substances 0.000 description 2
- 239000011148 porous material Substances 0.000 description 2
- 239000003755 preservative agent Substances 0.000 description 2
- GMVPRGQOIOIIMI-DWKJAMRDSA-N prostaglandin E1 Chemical compound CCCCC[C@H](O)\C=C\[C@H]1[C@H](O)CC(=O)[C@@H]1CCCCCCC(O)=O GMVPRGQOIOIIMI-DWKJAMRDSA-N 0.000 description 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
- NPRDHMWYZHSAHR-UHFFFAOYSA-N pyridine;trioxochromium Chemical compound O=[Cr](=O)=O.C1=CC=NC=C1.C1=CC=NC=C1 NPRDHMWYZHSAHR-UHFFFAOYSA-N 0.000 description 2
- 238000007363 ring formation reaction Methods 0.000 description 2
- 239000000741 silica gel Substances 0.000 description 2
- 229910002027 silica gel Inorganic materials 0.000 description 2
- 229960001866 silicon dioxide Drugs 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 239000008247 solid mixture Substances 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- 230000001954 sterilising effect Effects 0.000 description 2
- 238000004659 sterilization and disinfection Methods 0.000 description 2
- 238000006467 substitution reaction Methods 0.000 description 2
- 239000004094 surface-active agent Substances 0.000 description 2
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
- FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 2
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
- 125000003944 tolyl group Chemical group 0.000 description 2
- GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 2
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 2
- 239000000080 wetting agent Substances 0.000 description 2
- 125000005023 xylyl group Chemical group 0.000 description 2
- AOSZTAHDEDLTLQ-AZKQZHLXSA-N (1S,2S,4R,8S,9S,11S,12R,13S,19S)-6-[(3-chlorophenyl)methyl]-12,19-difluoro-11-hydroxy-8-(2-hydroxyacetyl)-9,13-dimethyl-6-azapentacyclo[10.8.0.02,9.04,8.013,18]icosa-14,17-dien-16-one Chemical compound C([C@@H]1C[C@H]2[C@H]3[C@]([C@]4(C=CC(=O)C=C4[C@@H](F)C3)C)(F)[C@@H](O)C[C@@]2([C@@]1(C1)C(=O)CO)C)N1CC1=CC=CC(Cl)=C1 AOSZTAHDEDLTLQ-AZKQZHLXSA-N 0.000 description 1
- GLGNXYJARSMNGJ-VKTIVEEGSA-N (1s,2s,3r,4r)-3-[[5-chloro-2-[(1-ethyl-6-methoxy-2-oxo-4,5-dihydro-3h-1-benzazepin-7-yl)amino]pyrimidin-4-yl]amino]bicyclo[2.2.1]hept-5-ene-2-carboxamide Chemical compound CCN1C(=O)CCCC2=C(OC)C(NC=3N=C(C(=CN=3)Cl)N[C@H]3[C@H]([C@@]4([H])C[C@@]3(C=C4)[H])C(N)=O)=CC=C21 GLGNXYJARSMNGJ-VKTIVEEGSA-N 0.000 description 1
- SZUVGFMDDVSKSI-WIFOCOSTSA-N (1s,2s,3s,5r)-1-(carboxymethyl)-3,5-bis[(4-phenoxyphenyl)methyl-propylcarbamoyl]cyclopentane-1,2-dicarboxylic acid Chemical compound O=C([C@@H]1[C@@H]([C@](CC(O)=O)([C@H](C(=O)N(CCC)CC=2C=CC(OC=3C=CC=CC=3)=CC=2)C1)C(O)=O)C(O)=O)N(CCC)CC(C=C1)=CC=C1OC1=CC=CC=C1 SZUVGFMDDVSKSI-WIFOCOSTSA-N 0.000 description 1
- GHYOCDFICYLMRF-UTIIJYGPSA-N (2S,3R)-N-[(2S)-3-(cyclopenten-1-yl)-1-[(2R)-2-methyloxiran-2-yl]-1-oxopropan-2-yl]-3-hydroxy-3-(4-methoxyphenyl)-2-[[(2S)-2-[(2-morpholin-4-ylacetyl)amino]propanoyl]amino]propanamide Chemical compound C1(=CCCC1)C[C@@H](C(=O)[C@@]1(OC1)C)NC([C@H]([C@@H](C1=CC=C(C=C1)OC)O)NC([C@H](C)NC(CN1CCOCC1)=O)=O)=O GHYOCDFICYLMRF-UTIIJYGPSA-N 0.000 description 1
- QFLWZFQWSBQYPS-AWRAUJHKSA-N (3S)-3-[[(2S)-2-[[(2S)-2-[5-[(3aS,6aR)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]pentanoylamino]-3-methylbutanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-4-[1-bis(4-chlorophenoxy)phosphorylbutylamino]-4-oxobutanoic acid Chemical compound CCCC(NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@@H](NC(=O)CCCCC1SC[C@@H]2NC(=O)N[C@H]12)C(C)C)P(=O)(Oc1ccc(Cl)cc1)Oc1ccc(Cl)cc1 QFLWZFQWSBQYPS-AWRAUJHKSA-N 0.000 description 1
- IWZSHWBGHQBIML-ZGGLMWTQSA-N (3S,8S,10R,13S,14S,17S)-17-isoquinolin-7-yl-N,N,10,13-tetramethyl-2,3,4,7,8,9,11,12,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-3-amine Chemical compound CN(C)[C@H]1CC[C@]2(C)C3CC[C@@]4(C)[C@@H](CC[C@@H]4c4ccc5ccncc5c4)[C@@H]3CC=C2C1 IWZSHWBGHQBIML-ZGGLMWTQSA-N 0.000 description 1
- PXGPLTODNUVGFL-BRIYLRKRSA-N (E,Z)-(1R,2R,3R,5S)-7-(3,5-Dihydroxy-2-((3S)-(3-hydroxy-1-octenyl))cyclopentyl)-5-heptenoic acid Chemical compound CCCCC[C@H](O)C=C[C@H]1[C@H](O)C[C@H](O)[C@@H]1CC=CCCCC(O)=O PXGPLTODNUVGFL-BRIYLRKRSA-N 0.000 description 1
- NIRHEUUFSAUPIO-TWUSMTIXSA-N (z)-9-[(1r,2r,3r)-2-(4,4-difluoro-3-oxooctyl)-3-hydroxy-5-oxocyclopentyl]non-7-enoic acid Chemical compound CCCCC(F)(F)C(=O)CC[C@H]1[C@H](O)CC(=O)[C@@H]1C\C=C/CCCCCC(O)=O NIRHEUUFSAUPIO-TWUSMTIXSA-N 0.000 description 1
- ONBQEOIKXPHGMB-VBSBHUPXSA-N 1-[2-[(2s,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]oxy-4,6-dihydroxyphenyl]-3-(4-hydroxyphenyl)propan-1-one Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1OC1=CC(O)=CC(O)=C1C(=O)CCC1=CC=C(O)C=C1 ONBQEOIKXPHGMB-VBSBHUPXSA-N 0.000 description 1
- HXKKHQJGJAFBHI-UHFFFAOYSA-N 1-aminopropan-2-ol Chemical class CC(O)CN HXKKHQJGJAFBHI-UHFFFAOYSA-N 0.000 description 1
- BCRKBAANNQLPBT-UHFFFAOYSA-N 1-dimethoxyphosphoryl-3,3-difluorononan-2-one Chemical compound CCCCCCC(F)(F)C(=O)CP(=O)(OC)OC BCRKBAANNQLPBT-UHFFFAOYSA-N 0.000 description 1
- LQZCYXCHWNQBKX-UHFFFAOYSA-N 1-dimethoxyphosphorylheptan-2-one Chemical compound CCCCCC(=O)CP(=O)(OC)OC LQZCYXCHWNQBKX-UHFFFAOYSA-N 0.000 description 1
- VXPBDCBTMSKCKZ-XQHNHVHJSA-N 15-dehydro-prostaglandin E1 Chemical compound CCCCCC(=O)\C=C\[C@H]1[C@H](O)CC(=O)[C@@H]1CCCCCCC(O)=O VXPBDCBTMSKCKZ-XQHNHVHJSA-N 0.000 description 1
- QAOBBBBDJSWHMU-WMBBNPMCSA-N 16,16-dimethylprostaglandin E2 Chemical compound CCCCC(C)(C)[C@H](O)\C=C\[C@H]1[C@H](O)CC(=O)[C@@H]1C\C=C/CCCC(O)=O QAOBBBBDJSWHMU-WMBBNPMCSA-N 0.000 description 1
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 description 1
- 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- JLLYLQLDYORLBB-UHFFFAOYSA-N 5-bromo-n-methylthiophene-2-sulfonamide Chemical compound CNS(=O)(=O)C1=CC=C(Br)S1 JLLYLQLDYORLBB-UHFFFAOYSA-N 0.000 description 1
- GLIZUTURRHNTMF-UHFFFAOYSA-N 6-carboxyhex-2-enyl(triphenyl)phosphanium;bromide Chemical compound [Br-].C=1C=CC=CC=1[P+](C=1C=CC=CC=1)(CC=CCCCC(=O)O)C1=CC=CC=C1 GLIZUTURRHNTMF-UHFFFAOYSA-N 0.000 description 1
- WCZUXNBRBZFNPY-UHFFFAOYSA-N 6-carboxyhex-3-enyl(triphenyl)phosphanium;bromide Chemical compound [Br-].C=1C=CC=CC=1[P+](C=1C=CC=CC=1)(CCC=CCCC(=O)O)C1=CC=CC=C1 WCZUXNBRBZFNPY-UHFFFAOYSA-N 0.000 description 1
- HVVQSKCGHAPHMV-UHFFFAOYSA-N 7-bromoheptanenitrile Chemical compound BrCCCCCCC#N HVVQSKCGHAPHMV-UHFFFAOYSA-N 0.000 description 1
- FMKNXQAUFDRBNP-UHFFFAOYSA-N CCCCCC(COP(O)=O)=O Chemical compound CCCCCC(COP(O)=O)=O FMKNXQAUFDRBNP-UHFFFAOYSA-N 0.000 description 1
- 101100310593 Candida albicans (strain SC5314 / ATCC MYA-2876) SOD4 gene Proteins 0.000 description 1
- 239000004215 Carbon black (E152) Substances 0.000 description 1
- 206010007749 Cataract diabetic Diseases 0.000 description 1
- 206010007766 Cataract traumatic Diseases 0.000 description 1
- 229940126657 Compound 17 Drugs 0.000 description 1
- 229910021595 Copper(I) iodide Inorganic materials 0.000 description 1
- YXHKONLOYHBTNS-UHFFFAOYSA-N Diazomethane Chemical compound C=[N+]=[N-] YXHKONLOYHBTNS-UHFFFAOYSA-N 0.000 description 1
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 description 1
- 239000005977 Ethylene Substances 0.000 description 1
- PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical class NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 1
- RRSNDVCODIMOFX-MPKOGUQCSA-N Fc1c(Cl)cccc1[C@H]1[C@@H](NC2(CCCCC2)[C@@]11C(=O)Nc2cc(Cl)ccc12)C(=O)Nc1ccc(cc1)C(=O)NCCCCCc1cccc2C(=O)N(Cc12)C1CCC(=O)NC1=O Chemical compound Fc1c(Cl)cccc1[C@H]1[C@@H](NC2(CCCCC2)[C@@]11C(=O)Nc2cc(Cl)ccc12)C(=O)Nc1ccc(cc1)C(=O)NCCCCCc1cccc2C(=O)N(Cc12)C1CCC(=O)NC1=O RRSNDVCODIMOFX-MPKOGUQCSA-N 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 1
- 206010020772 Hypertension Diseases 0.000 description 1
- 208000001953 Hypotension Diseases 0.000 description 1
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical class NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- NGRZMGCGHOSCBJ-UHFFFAOYSA-N OC(CCCCC(C=CC=C1)=C1P(C1=CC=CC=C1)C1=CC=CC=C1)=O.Br Chemical compound OC(CCCCC(C=CC=C1)=C1P(C1=CC=CC=C1)C1=CC=CC=C1)=O.Br NGRZMGCGHOSCBJ-UHFFFAOYSA-N 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- QOSMNYMQXIVWKY-UHFFFAOYSA-N Propyl levulinate Chemical compound CCCOC(=O)CCC(C)=O QOSMNYMQXIVWKY-UHFFFAOYSA-N 0.000 description 1
- MYHXHCUNDDAEOZ-UHFFFAOYSA-N Prostaglandin A&2% Natural products CCCCCC(O)C=CC1C=CC(=O)C1CC=CCCCC(O)=O MYHXHCUNDDAEOZ-UHFFFAOYSA-N 0.000 description 1
- 206010037756 Radiation cataract Diseases 0.000 description 1
- 101100190148 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) PGA2 gene Proteins 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- 244000299461 Theobroma cacao Species 0.000 description 1
- 235000005764 Theobroma cacao ssp. cacao Nutrition 0.000 description 1
- 235000005767 Theobroma cacao ssp. sphaerocarpum Nutrition 0.000 description 1
- 206010044135 Toxic cataract Diseases 0.000 description 1
- 231100000329 Toxic cataract Toxicity 0.000 description 1
- GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical class OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 description 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
- LNUFLCYMSVYYNW-ZPJMAFJPSA-N [(2r,3r,4s,5r,6r)-2-[(2r,3r,4s,5r,6r)-6-[(2r,3r,4s,5r,6r)-6-[(2r,3r,4s,5r,6r)-6-[[(3s,5s,8r,9s,10s,13r,14s,17r)-10,13-dimethyl-17-[(2r)-6-methylheptan-2-yl]-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1h-cyclopenta[a]phenanthren-3-yl]oxy]-4,5-disulfo Chemical compound O([C@@H]1[C@@H](COS(O)(=O)=O)O[C@@H]([C@@H]([C@H]1OS(O)(=O)=O)OS(O)(=O)=O)O[C@@H]1[C@@H](COS(O)(=O)=O)O[C@@H]([C@@H]([C@H]1OS(O)(=O)=O)OS(O)(=O)=O)O[C@@H]1[C@@H](COS(O)(=O)=O)O[C@H]([C@@H]([C@H]1OS(O)(=O)=O)OS(O)(=O)=O)O[C@@H]1C[C@@H]2CC[C@H]3[C@@H]4CC[C@@H]([C@]4(CC[C@@H]3[C@@]2(C)CC1)C)[C@H](C)CCCC(C)C)[C@H]1O[C@H](COS(O)(=O)=O)[C@@H](OS(O)(=O)=O)[C@H](OS(O)(=O)=O)[C@H]1OS(O)(=O)=O LNUFLCYMSVYYNW-ZPJMAFJPSA-N 0.000 description 1
- QUXMPZUVBXHUII-UHFFFAOYSA-N [1,1-bis(hydroxymethylamino)ethylamino]methanol Chemical class OCNC(C)(NCO)NCO QUXMPZUVBXHUII-UHFFFAOYSA-N 0.000 description 1
- MRZAUHPKRKMSPG-UHFFFAOYSA-K [F-].[F-].[F-].C(CCC)[N+](CCCC)(CCCC)CCCC.C(CCC)[N+](CCCC)(CCCC)CCCC.C(CCC)[N+](CCCC)(CCCC)CCCC Chemical compound [F-].[F-].[F-].C(CCC)[N+](CCCC)(CCCC)CCCC.C(CCC)[N+](CCCC)(CCCC)CCCC.C(CCC)[N+](CCCC)(CCCC)CCCC MRZAUHPKRKMSPG-UHFFFAOYSA-K 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 125000002252 acyl group Chemical group 0.000 description 1
- 125000003158 alcohol group Chemical group 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 125000001931 aliphatic group Chemical group 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 1
- AZDRQVAHHNSJOQ-UHFFFAOYSA-N alumane Chemical compound [AlH3] AZDRQVAHHNSJOQ-UHFFFAOYSA-N 0.000 description 1
- WMGSQTMJHBYJMQ-UHFFFAOYSA-N aluminum;magnesium;silicate Chemical compound [Mg+2].[Al+3].[O-][Si]([O-])([O-])[O-] WMGSQTMJHBYJMQ-UHFFFAOYSA-N 0.000 description 1
- 235000019270 ammonium chloride Nutrition 0.000 description 1
- 150000003863 ammonium salts Chemical class 0.000 description 1
- 150000003931 anilides Chemical class 0.000 description 1
- 230000000767 anti-ulcer Effects 0.000 description 1
- 239000007900 aqueous suspension Substances 0.000 description 1
- 150000001483 arginine derivatives Chemical class 0.000 description 1
- 125000005228 aryl sulfonate group Chemical group 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 1
- 150000003939 benzylamines Chemical class 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 125000001246 bromo group Chemical group Br* 0.000 description 1
- 125000005997 bromomethyl group Chemical group 0.000 description 1
- 230000003182 bronchodilatating effect Effects 0.000 description 1
- 239000008366 buffered solution Substances 0.000 description 1
- 235000014121 butter Nutrition 0.000 description 1
- 235000001046 cacaotero Nutrition 0.000 description 1
- RYYVLZVUVIJVGH-UHFFFAOYSA-N caffeine Chemical class CN1C(=O)N(C)C(=O)C2=C1N=CN2C RYYVLZVUVIJVGH-UHFFFAOYSA-N 0.000 description 1
- 235000013927 calcium gluconate Nutrition 0.000 description 1
- 159000000007 calcium salts Chemical class 0.000 description 1
- 150000001735 carboxylic acids Chemical class 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 229920005556 chlorobutyl Polymers 0.000 description 1
- 125000004218 chloromethyl group Chemical group [H]C([H])(Cl)* 0.000 description 1
- 238000004040 coloring Methods 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 229940125773 compound 10 Drugs 0.000 description 1
- 229940125797 compound 12 Drugs 0.000 description 1
- 229940126543 compound 14 Drugs 0.000 description 1
- 229940125758 compound 15 Drugs 0.000 description 1
- 229940126142 compound 16 Drugs 0.000 description 1
- 229940125782 compound 2 Drugs 0.000 description 1
- 229940126214 compound 3 Drugs 0.000 description 1
- 238000013329 compounding Methods 0.000 description 1
- 150000004699 copper complex Chemical class 0.000 description 1
- LSXDOTMGLUJQCM-UHFFFAOYSA-M copper(i) iodide Chemical compound I[Cu] LSXDOTMGLUJQCM-UHFFFAOYSA-M 0.000 description 1
- 125000002592 cumenyl group Chemical group C1(=C(C=CC=C1)*)C(C)C 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- 150000003946 cyclohexylamines Chemical class 0.000 description 1
- 238000006704 dehydrohalogenation reaction Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 201000007025 diabetic cataract Diseases 0.000 description 1
- ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical class OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 1
- 150000004656 dimethylamines Chemical class 0.000 description 1
- QKIUAMUSENSFQQ-UHFFFAOYSA-N dimethylazanide Chemical compound C[N-]C QKIUAMUSENSFQQ-UHFFFAOYSA-N 0.000 description 1
- 150000002009 diols Chemical class 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 239000002934 diuretic Substances 0.000 description 1
- 230000001882 diuretic effect Effects 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- ZCRZCMUDOWDGOB-UHFFFAOYSA-N ethanesulfonimidic acid Chemical compound CCS(N)(=O)=O ZCRZCMUDOWDGOB-UHFFFAOYSA-N 0.000 description 1
- 150000002169 ethanolamines Chemical class 0.000 description 1
- DZFYOYRNBGNPJW-UHFFFAOYSA-N ethoxythallium Chemical compound [Tl+].CC[O-] DZFYOYRNBGNPJW-UHFFFAOYSA-N 0.000 description 1
- OFGLXRANLNLCHY-HBMCJLEFSA-N ethyl 7-[(1r,2s,3s)-3-hydroxy-2-(7-methyl-3-oxooctyl)-5-oxocyclopentyl]-6-oxoheptanoate Chemical group CCOC(=O)CCCCC(=O)C[C@@H]1[C@H](CCC(=O)CCCC(C)C)[C@@H](O)CC1=O OFGLXRANLNLCHY-HBMCJLEFSA-N 0.000 description 1
- 125000004494 ethyl ester group Chemical group 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000019634 flavors Nutrition 0.000 description 1
- 125000004216 fluoromethyl group Chemical group [H]C([H])(F)* 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 235000011187 glycerol Nutrition 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 125000001188 haloalkyl group Chemical group 0.000 description 1
- 125000000623 heterocyclic group Chemical group 0.000 description 1
- GNOIPBMMFNIUFM-UHFFFAOYSA-N hexamethylphosphoric triamide Chemical compound CN(C)P(=O)(N(C)C)N(C)C GNOIPBMMFNIUFM-UHFFFAOYSA-N 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 125000001183 hydrocarbyl group Chemical group 0.000 description 1
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 description 1
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 1
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 1
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 1
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 1
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 1
- 230000001631 hypertensive effect Effects 0.000 description 1
- 208000021822 hypotensive Diseases 0.000 description 1
- 230000001077 hypotensive effect Effects 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 150000007529 inorganic bases Chemical class 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 125000002346 iodo group Chemical group I* 0.000 description 1
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- ZLVXBBHTMQJRSX-VMGNSXQWSA-N jdtic Chemical compound C1([C@]2(C)CCN(C[C@@H]2C)C[C@H](C(C)C)NC(=O)[C@@H]2NCC3=CC(O)=CC=C3C2)=CC=CC(O)=C1 ZLVXBBHTMQJRSX-VMGNSXQWSA-N 0.000 description 1
- 239000010410 layer Substances 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- UBJFKNSINUCEAL-UHFFFAOYSA-N lithium;2-methylpropane Chemical compound [Li+].C[C-](C)C UBJFKNSINUCEAL-UHFFFAOYSA-N 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 159000000003 magnesium salts Chemical class 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- HNQIVZYLYMDVSB-UHFFFAOYSA-N methanesulfonimidic acid Chemical compound CS(N)(=O)=O HNQIVZYLYMDVSB-UHFFFAOYSA-N 0.000 description 1
- NBTOZLQBSIZIKS-UHFFFAOYSA-N methoxide Chemical compound [O-]C NBTOZLQBSIZIKS-UHFFFAOYSA-N 0.000 description 1
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 1
- CBZINEMIDCLHAY-SNHXEXRGSA-N methyl (Z)-7-[(1R,2R,3R,5S)-3,5-dihydroxy-2-(3-oxononyl)cyclopentyl]hept-5-enoate Chemical group CCCCCCC(=O)CC[C@H]1[C@H](O)C[C@H](O)[C@@H]1C\C=C/CCCC(=O)OC CBZINEMIDCLHAY-SNHXEXRGSA-N 0.000 description 1
- 150000003956 methylamines Chemical class 0.000 description 1
- MGJXBDMLVWIYOQ-UHFFFAOYSA-N methylazanide Chemical compound [NH-]C MGJXBDMLVWIYOQ-UHFFFAOYSA-N 0.000 description 1
- 239000012457 nonaqueous media Substances 0.000 description 1
- 239000002736 nonionic surfactant Substances 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 235000021590 normal diet Nutrition 0.000 description 1
- 235000016709 nutrition Nutrition 0.000 description 1
- 239000003883 ointment base Substances 0.000 description 1
- 239000004006 olive oil Substances 0.000 description 1
- 235000008390 olive oil Nutrition 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 239000012044 organic layer Substances 0.000 description 1
- 125000001181 organosilyl group Chemical group [SiH3]* 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 239000002304 perfume Substances 0.000 description 1
- LIGACIXOYTUXAW-UHFFFAOYSA-N phenacyl bromide Chemical compound BrCC(=O)C1=CC=CC=C1 LIGACIXOYTUXAW-UHFFFAOYSA-N 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- 150000003053 piperidines Chemical class 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229920000136 polysorbate Polymers 0.000 description 1
- 229940068965 polysorbates Drugs 0.000 description 1
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 1
- LJCNRYVRMXRIQR-OLXYHTOASA-L potassium sodium L-tartrate Chemical compound [Na+].[K+].[O-]C(=O)[C@H](O)[C@@H](O)C([O-])=O LJCNRYVRMXRIQR-OLXYHTOASA-L 0.000 description 1
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 238000003822 preparative gas chromatography Methods 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- MFDFERRIHVXMIY-UHFFFAOYSA-N procaine Chemical class CCN(CC)CCOC(=O)C1=CC=C(N)C=C1 MFDFERRIHVXMIY-UHFFFAOYSA-N 0.000 description 1
- RRUYLMFSYDCRIZ-ADMXILSSSA-N propan-2-yl (z)-9-[(1r,2r,3r)-3-hydroxy-5-oxo-2-(3-oxodecyl)cyclopentyl]non-7-enoate Chemical compound CCCCCCCC(=O)CC[C@H]1[C@H](O)CC(=O)[C@@H]1C\C=C/CCCCCC(=O)OC(C)C RRUYLMFSYDCRIZ-ADMXILSSSA-N 0.000 description 1
- 235000010409 propane-1,2-diol alginate Nutrition 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- MYHXHCUNDDAEOZ-FOSBLDSVSA-N prostaglandin A2 Chemical compound CCCCC[C@H](O)\C=C\[C@H]1C=CC(=O)[C@@H]1C\C=C/CCCC(O)=O MYHXHCUNDDAEOZ-FOSBLDSVSA-N 0.000 description 1
- QLPYHQHJKMTHED-UHFFFAOYSA-N prostaglandin E1 methyl ester Natural products CCCCCC(O)C=CC1C(O)CC(=O)C1CCCCCCC(=O)OC QLPYHQHJKMTHED-UHFFFAOYSA-N 0.000 description 1
- WGCXTGBZBFBQPP-UHFFFAOYSA-N prostaglandin E2 methyl ester Natural products CCCCCC(O)C=CC1C(O)CC(=O)C1CC=CCCCC(=O)OC WGCXTGBZBFBQPP-UHFFFAOYSA-N 0.000 description 1
- 239000008213 purified water Substances 0.000 description 1
- 230000005855 radiation Effects 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 229940100618 rectal suppository Drugs 0.000 description 1
- 239000006215 rectal suppository Substances 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 239000012266 salt solution Substances 0.000 description 1
- DCKVNWZUADLDEH-UHFFFAOYSA-N sec-butyl acetate Chemical compound CCC(C)OC(C)=O DCKVNWZUADLDEH-UHFFFAOYSA-N 0.000 description 1
- 201000008525 senile cataract Diseases 0.000 description 1
- WBHQBSYUUJJSRZ-UHFFFAOYSA-M sodium bisulfate Chemical compound [Na+].OS([O-])(=O)=O WBHQBSYUUJJSRZ-UHFFFAOYSA-M 0.000 description 1
- 229910000342 sodium bisulfate Inorganic materials 0.000 description 1
- 235000011006 sodium potassium tartrate Nutrition 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 125000003107 substituted aryl group Chemical group 0.000 description 1
- 229940124530 sulfonamide Drugs 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000002511 suppository base Substances 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- BCNZYOJHNLTNEZ-UHFFFAOYSA-N tert-butyldimethylsilyl chloride Chemical compound CC(C)(C)[Si](C)(C)Cl BCNZYOJHNLTNEZ-UHFFFAOYSA-N 0.000 description 1
- 125000001981 tert-butyldimethylsilyl group Chemical group [H]C([H])([H])[Si]([H])(C([H])([H])[H])[*]C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 150000005621 tetraalkylammonium salts Chemical class 0.000 description 1
- 229910052716 thallium Inorganic materials 0.000 description 1
- BKVIYDNLLOSFOA-UHFFFAOYSA-N thallium Chemical compound [Tl] BKVIYDNLLOSFOA-UHFFFAOYSA-N 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- TUQOTMZNTHZOKS-UHFFFAOYSA-N tributylphosphine Chemical compound CCCCP(CCCC)CCCC TUQOTMZNTHZOKS-UHFFFAOYSA-N 0.000 description 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
- 125000003258 trimethylene group Chemical group [H]C([H])([*:2])C([H])([H])C([H])([H])[*:1] 0.000 description 1
- 229940120293 vaginal suppository Drugs 0.000 description 1
- 239000006216 vaginal suppository Substances 0.000 description 1
- 230000000304 vasodilatating effect Effects 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 229920001567 vinyl ester resin Polymers 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
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
- A61K31/5575—Eicosanoids, e.g. leukotrienes or prostaglandins having a cyclopentane, e.g. prostaglandin E2, prostaglandin F2-alpha
-
- 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
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/06—Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Applications Claiming Priority (6)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP90895/1990 | 1990-04-04 | ||
| JP9089590 | 1990-04-04 | ||
| JP221646/1990 | 1990-08-22 | ||
| JP22164690 | 1990-08-22 | ||
| JP2931091 | 1991-01-29 | ||
| JP29310/1991 | 1991-01-29 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2039420A1 CA2039420A1 (en) | 1991-10-05 |
| CA2039420C true CA2039420C (en) | 1996-12-10 |
Family
ID=27286510
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002039420A Expired - Lifetime CA2039420C (en) | 1990-04-04 | 1991-03-28 | Treatment of cataract with 15-keto-prostaglandin compounds |
Country Status (11)
Families Citing this family (54)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| TW205508B (GUID-C5D7CC26-194C-43D0-91A1-9AE8C70A9BFF.html) * | 1990-08-02 | 1993-05-11 | Kabushikaisha Ueno Seiyaku Oyo Kenkyujo | |
| US5352708A (en) * | 1992-09-21 | 1994-10-04 | Allergan, Inc. | Non-acidic cyclopentane heptanoic acid, 2-cycloalkyl or arylalkyl derivatives as therapeutic agents |
| US5688819A (en) * | 1992-09-21 | 1997-11-18 | Allergan | Cyclopentane heptanoic acid, 2-cycloalkyl or arylalkyl derivatives as therapeutic agents |
| US5972991A (en) | 1992-09-21 | 1999-10-26 | Allergan | Cyclopentane heptan(ene) oic acid, 2-heteroarylalkenyl derivatives as therapeutic agents |
| US5328933A (en) * | 1992-10-28 | 1994-07-12 | Allergan, Inc. | Cyclopentane heptenylnitro and heptanylnitro-2-aliphatic or aryl aliphatic derivatives and homologues |
| SE9303627D0 (sv) * | 1993-11-03 | 1993-11-03 | Kabi Pharmacia Ab | Method and means for prevention of cataract |
| ATE315939T1 (de) * | 1993-11-19 | 2006-02-15 | Univ Sydney | Verfahren zur prophylaxe oder kontrolle des katarakts |
| SE9403160D0 (sv) * | 1994-09-21 | 1994-09-21 | Pharmacia Ab | Method and means for prevention and treatment of secondary cataract |
| WO1997047595A1 (fr) * | 1996-06-10 | 1997-12-18 | R-Tech Ueno, Ltd. | Antagoniste de l'endotheline |
| TR200000673T2 (tr) * | 1997-09-09 | 2000-11-21 | The Procter & Gamble Company | FP agonistleri olarak yararlı aromatik C16-C20- ikameli tetrahidro prostaglandinler. |
| EP1012136B1 (en) * | 1997-09-09 | 2004-07-07 | Duke University | Aromatic c 16?-c 20?-substituted tetrahydro prostaglandins useful as fp agonists |
| AU739343B2 (en) | 1997-11-28 | 2001-10-11 | Sucampo Ag | Endothelin antagonist |
| WO2000051980A1 (en) | 1999-03-05 | 2000-09-08 | The Procter & Gamble Company | C16 unsaturated fp-selective prostaglandins analogs |
| TWI225398B (en) * | 1999-07-14 | 2004-12-21 | R Tech Ueno Ltd | Composition for treatment of external secretion disorders |
| US6458836B1 (en) | 2000-03-16 | 2002-10-01 | Sucampo, A.G. | Treatment of ocular hypertension and glaucoma |
| MXPA02008967A (es) * | 2000-03-16 | 2003-02-12 | Sucampo Ag | Tratamiento de hipertension ocular y glaucoma. |
| AR030275A1 (es) | 2000-03-24 | 2003-08-20 | Sucampo Pharmaceuticals Inc | Composicion que inhibe la apoptosis y uso de un compuesto 15-ceto-prostaglandina- para producirla |
| US20020172693A1 (en) * | 2000-03-31 | 2002-11-21 | Delong Michell Anthony | Compositions and methods for treating hair loss using non-naturally occurring prostaglandins |
| US20020037914A1 (en) * | 2000-03-31 | 2002-03-28 | Delong Mitchell Anthony | Compositions and methods for treating hair loss using C16-C20 aromatic tetrahydro prostaglandins |
| US20020146439A1 (en) * | 2000-03-31 | 2002-10-10 | Delong Mitchell Anthony | Compositions and methods for treating hair loss using oximyl and hydroxylamino prostaglandins |
| US20020013294A1 (en) * | 2000-03-31 | 2002-01-31 | Delong Mitchell Anthony | Cosmetic and pharmaceutical compositions and methods using 2-decarboxy-2-phosphinico derivatives |
| MXPA02009915A (es) * | 2000-04-06 | 2003-03-27 | Sucampo Ag | Composicion promotora de secrecion de bilis. |
| TWI302100B (en) | 2001-05-02 | 2008-10-21 | Sucampo Ag | Composition for treating drug-induced constipation |
| EP1420793A1 (en) * | 2001-08-23 | 2004-05-26 | Sucampo AG | Method and composition for treatment of ocular hypertension and glaucoma |
| EP1420794B1 (en) | 2001-08-31 | 2017-12-27 | Sucampo AG | Prostaglandin analogs as chloride channel openers |
| WO2005018646A1 (ja) | 2003-08-21 | 2005-03-03 | Sucampo Ag | 眼科用組成物 |
| US8580851B2 (en) | 2002-08-21 | 2013-11-12 | Sucampo Ag | Ophthalmic solution |
| AU2003274735B2 (en) * | 2002-10-23 | 2008-12-04 | Sucampo Ag | Prostaglandin compounds for the treatment of obesity |
| KR101164838B1 (ko) | 2002-12-27 | 2012-07-11 | 수캄포 아게 | 복부 불쾌감 치료용 프로스타글랜딘의 유도체 |
| ATE489096T1 (de) * | 2003-07-03 | 2010-12-15 | Sucampo Ag | Pharmazeutische magensaftresistent überzogene zusammensetzung enthaltend prostaglandin-analoga als chloridkanalöffner |
| TWI495471B (zh) * | 2003-08-12 | 2015-08-11 | R Tech Ueno Ltd | 促進毛髮生長之組成物及方法 |
| SE0303179D0 (sv) * | 2003-11-26 | 2003-11-26 | Astrazeneca Ab | Novel compounds |
| US7321057B2 (en) * | 2004-08-02 | 2008-01-22 | R-Tech Ueno, Ltd. | Method for manufacturing prostaglandin analogue |
| CN101146541B (zh) | 2005-01-27 | 2012-04-11 | 苏坎波公司 | 用于治疗中枢神经系统疾病的方法和组合物 |
| AR055038A1 (es) | 2005-03-04 | 2007-08-01 | Sucampo Ag | Metodo y compuesto para tratar enfermedades vasculares perifericas |
| WO2010102078A1 (en) | 2009-03-04 | 2010-09-10 | Allergan, Inc. | Enhanced bimatoprost ophthalmic solution |
| US7851504B2 (en) | 2005-03-16 | 2010-12-14 | Allergan, Inc. | Enhanced bimatoprost ophthalmic solution |
| US20060281818A1 (en) | 2005-03-21 | 2006-12-14 | Sucampo Ag, North Carolina State University | Method for treating mucosal disorders |
| AU2006234632B2 (en) * | 2005-04-12 | 2011-10-27 | Sucampo Ag | Combined use of prostaglandin compound and proton pump inhibitor for the treatment of gastrointestinal disorders |
| MX2008009652A (es) | 2006-01-24 | 2008-11-06 | R Tech Ueno Ltd | Composicion farmaceutica que comprende un compuesto biciclico y metodo para estabilizar el compuesto biciclico. |
| CN104971056A (zh) | 2006-01-24 | 2015-10-14 | 株式会社·R-技术上野 | 软明胶胶囊制剂 |
| US20090062381A1 (en) | 2006-03-13 | 2009-03-05 | Ryu Hirata | Aqueous composition |
| US8871752B2 (en) * | 2008-02-19 | 2014-10-28 | Sucampo Ag | Method for modulating stem cell growth |
| US8722739B2 (en) * | 2008-10-29 | 2014-05-13 | Novaer Holdings, Inc. | Amino acid salts of prostaglandins |
| US8623918B2 (en) * | 2008-10-29 | 2014-01-07 | Novaer Holdings, Inc. | Amino acid salts of prostaglandins |
| US8609729B2 (en) * | 2009-04-15 | 2013-12-17 | Sucampo Ag | Method for treating macular degeneration |
| US8569279B2 (en) * | 2009-05-27 | 2013-10-29 | Sucampo Ag | Method for modulating claudin mediated functions |
| US9084815B2 (en) * | 2009-09-16 | 2015-07-21 | Sucampo Ag | Method for treating damage induced by an anti-tumor agent, treating mucositis and treating tumor |
| US9522153B2 (en) | 2009-12-22 | 2016-12-20 | Allergan, Inc. | Compositions and methods for lowering intraocular pressure |
| CA2830626A1 (en) | 2011-04-07 | 2012-10-11 | Sucampo Ag | Method for treating asthenopia |
| BR112014002712A8 (pt) | 2011-08-05 | 2017-06-20 | Sucampo Ag | método para tratamento da esquizofrenia |
| AR092821A1 (es) | 2012-04-20 | 2015-05-06 | Sucampo Ag | Conjugado de derivado de acido graso-polimero |
| US20150057351A1 (en) | 2013-08-22 | 2015-02-26 | Sucampo Ag | Method for treating neuropathic pain |
| US20170020890A1 (en) | 2015-06-19 | 2017-01-26 | Sucampo Ag | Pharmaceutical composition comprising fatty acid derivative |
Family Cites Families (16)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3505386A (en) * | 1965-12-29 | 1970-04-07 | Upjohn Co | Compounds related to prostaglandins |
| US3974195A (en) * | 1974-10-02 | 1976-08-10 | The Upjohn Company | 2A,2B-Dihomo-15-alkyl-PGF2.sub.α analogs |
| EP0153858A3 (en) * | 1984-02-29 | 1985-12-11 | The Upjohn Company | The therapeutic use of prostaglandins |
| CA1322749C (en) * | 1987-01-28 | 1993-10-05 | Ryuzo Ueno | Prostaglandins of the d series, and tranquilizers and soporifics containing the same |
| CA1323364C (en) * | 1987-01-28 | 1993-10-19 | Ryuzo Ueno | Prostaglandins e and anti ulcer agents containing same |
| CA1324129C (en) * | 1987-04-30 | 1993-11-09 | Ryuzo Ueno | Prostaglandins of the f series |
| DE3869471D1 (de) * | 1987-05-15 | 1992-04-30 | Ueno Seiyaku Oyo Kenkyujo Kk | Fiebersteigende zusammensetzung. |
| ATE82499T1 (de) * | 1987-09-18 | 1992-12-15 | R Tech Ueno Ltd | Okulare hypotensivagenzien. |
| DE3873007T2 (de) * | 1987-10-02 | 1992-12-03 | Ueno Seiyaku Oyo Kenkyujo Kk | Kathartica. |
| JP2597629B2 (ja) * | 1988-02-26 | 1997-04-09 | 株式会社 上野製薬応用研究所 | １３，１４−ジヒドロ−１５−ケトプロスタグランジン類の安定化 |
| AU619543B2 (en) * | 1988-05-11 | 1992-01-30 | Sucampo Ag | Use of 15-ketoprostaglandin e or f compounds for uterine contraction |
| JP2597649B2 (ja) * | 1988-05-11 | 1997-04-09 | 株式会社上野製薬応用研究所 | 気管・気管支拡張剤 |
| ES2055051T3 (es) * | 1988-05-23 | 1994-08-16 | Ueno Seiyaku Oyo Kenkyujo Kk | Un metodo para la fabricacion de un medicamento eficaz para aumentar la presion sanguinea. |
| AU604156B2 (en) * | 1988-09-14 | 1990-12-06 | R-Tech Ueno, Ltd. | Prostaglandins of the F series |
| EP0580268B1 (en) * | 1988-10-01 | 1998-01-14 | R-Tech Ueno Ltd. | Ocular hypotensive agents |
| TW205508B (GUID-C5D7CC26-194C-43D0-91A1-9AE8C70A9BFF.html) * | 1990-08-02 | 1993-05-11 | Kabushikaisha Ueno Seiyaku Oyo Kenkyujo |
-
1991
- 1991-03-28 TW TW081106617A patent/TW249226B/zh not_active IP Right Cessation
- 1991-03-28 CA CA002039420A patent/CA2039420C/en not_active Expired - Lifetime
- 1991-03-28 TW TW080102419A patent/TW224942B/zh not_active IP Right Cessation
- 1991-04-03 US US07/680,187 patent/US5212324A/en not_active Expired - Lifetime
- 1991-04-03 DE DE69129921T patent/DE69129921T2/de not_active Expired - Lifetime
- 1991-04-03 AU AU74047/91A patent/AU644148B2/en not_active Expired
- 1991-04-03 ES ES91302925T patent/ES2119762T3/es not_active Expired - Lifetime
- 1991-04-03 EP EP91302925A patent/EP0453127B1/en not_active Expired - Lifetime
- 1991-04-03 AT AT91302925T patent/ATE169219T1/de not_active IP Right Cessation
- 1991-04-03 DK DK91302925T patent/DK0453127T3/da active
- 1991-04-04 KR KR1019910005502A patent/KR970005172B1/ko not_active Expired - Lifetime
-
1994
- 1994-09-06 US US08/300,541 patent/US5686487A/en not_active Expired - Lifetime
-
1998
- 1998-08-19 GR GR980400874T patent/GR3027666T3/el unknown
Also Published As
| Publication number | Publication date |
|---|---|
| KR970005172B1 (ko) | 1997-04-14 |
| TW249226B (GUID-C5D7CC26-194C-43D0-91A1-9AE8C70A9BFF.html) | 1995-06-11 |
| ES2119762T3 (es) | 1998-10-16 |
| EP0453127A2 (en) | 1991-10-23 |
| US5212324A (en) | 1993-05-18 |
| AU7404791A (en) | 1991-10-10 |
| DE69129921T2 (de) | 1999-01-14 |
| GR3027666T3 (en) | 1998-11-30 |
| US5686487A (en) | 1997-11-11 |
| KR910018027A (ko) | 1991-11-30 |
| CA2039420A1 (en) | 1991-10-05 |
| ATE169219T1 (de) | 1998-08-15 |
| EP0453127B1 (en) | 1998-08-05 |
| EP0453127A3 (en) | 1992-12-09 |
| DE69129921D1 (de) | 1998-09-10 |
| DK0453127T3 (da) | 1998-10-26 |
| AU644148B2 (en) | 1993-12-02 |
| TW224942B (GUID-C5D7CC26-194C-43D0-91A1-9AE8C70A9BFF.html) | 1994-06-11 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CA2039420C (en) | Treatment of cataract with 15-keto-prostaglandin compounds | |
| US5432174A (en) | Treatment of ocular hypertension | |
| EP0503887B1 (en) | Promotion of wound-healing with 15-keto-prostaglandin compounds | |
| US5164415A (en) | Treatment of pancreatic disease with 15-keto-prostaglandin compounds | |
| EP0467564B1 (en) | Treatment of inflammatory diseases with 15-keto-prostaglandin compounds | |
| EP0342003B1 (en) | Use of 15-ketoprostaglandin e or f compounds for uterine contraction | |
| EP0458588A1 (en) | Treatment of ocular hypertension with a synergistic combination for ocular administration | |
| KR0127297B1 (ko) | 15-케토-프로스타글란딘 화합물을 이용한 간 담즙성 질병의 치료 | |
| US5397797A (en) | Treatment of ocular hypertension with an ocular synergistic combination | |
| CA2042937C (en) | Treatment of ocular hypertension with a synergistic combination | |
| EP0430551B1 (en) | Treatment of cardiac dysfunction with 15-keto-prostaglandin compounds | |
| EP0469782B1 (en) | Treatment of cataract with prostacyclin compounds | |
| EP0458587A1 (en) | Synergistic combination for ophthalmic use | |
| US5175189A (en) | Treatment of ocular hypertension with a synergistic combination for ophthalmic use | |
| EP0410646B1 (en) | Treatment of hyperlipidemia with 15-keto-prostaglandin compounds |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request | ||
| MKEX | Expiry |