CA1328075C - Ocular hypotensive agents - Google Patents
Ocular hypotensive agentsInfo
- Publication number
- CA1328075C CA1328075C CA000577220A CA577220A CA1328075C CA 1328075 C CA1328075 C CA 1328075C CA 000577220 A CA000577220 A CA 000577220A CA 577220 A CA577220 A CA 577220A CA 1328075 C CA1328075 C CA 1328075C
- Authority
- CA
- Canada
- Prior art keywords
- dihydro
- keto
- prostaglandins
- ethyl
- ester
- 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
- 239000002220 antihypertensive agent Substances 0.000 title claims abstract description 19
- 229940094443 oxytocics prostaglandins Drugs 0.000 claims abstract description 32
- 150000003180 prostaglandins Chemical class 0.000 claims abstract description 18
- -1 hydroxy, hydroxy Chemical group 0.000 claims description 53
- 125000000217 alkyl group Chemical group 0.000 claims description 22
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 21
- 229920006395 saturated elastomer Polymers 0.000 claims description 10
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 8
- 150000003839 salts Chemical class 0.000 claims description 8
- 208000010412 Glaucoma Diseases 0.000 claims description 6
- 239000004480 active ingredient Substances 0.000 claims description 5
- 125000005843 halogen group Chemical group 0.000 claims description 5
- 125000005907 alkyl ester group Chemical class 0.000 claims description 4
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 4
- 229930195735 unsaturated hydrocarbon Natural products 0.000 claims description 4
- 125000003545 alkoxy group Chemical group 0.000 claims description 3
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 3
- 229930195734 saturated hydrocarbon Natural products 0.000 claims description 3
- 229910052736 halogen Inorganic materials 0.000 claims 2
- 125000006539 C12 alkyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims 1
- 150000002367 halogens Chemical group 0.000 claims 1
- 125000001183 hydrocarbyl group Chemical group 0.000 claims 1
- 230000004044 response Effects 0.000 abstract description 8
- 206010020772 Hypertension Diseases 0.000 abstract description 7
- 230000001631 hypertensive effect Effects 0.000 abstract description 7
- 230000001052 transient effect Effects 0.000 abstract description 7
- 150000001875 compounds Chemical class 0.000 description 46
- 239000003814 drug Substances 0.000 description 36
- 229940079593 drug Drugs 0.000 description 35
- 150000004702 methyl esters Chemical class 0.000 description 34
- 238000012360 testing method Methods 0.000 description 31
- 229960002986 dinoprostone Drugs 0.000 description 23
- 230000000694 effects Effects 0.000 description 21
- 150000002430 hydrocarbons Chemical group 0.000 description 18
- 206010020565 Hyperaemia Diseases 0.000 description 17
- 230000004410 intraocular pressure Effects 0.000 description 17
- 238000002360 preparation method Methods 0.000 description 17
- 125000004494 ethyl ester group Chemical group 0.000 description 14
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 12
- 239000000047 product Substances 0.000 description 12
- 229910052799 carbon Inorganic materials 0.000 description 11
- 230000001077 hypotensive effect Effects 0.000 description 11
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 10
- 230000008859 change Effects 0.000 description 10
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 10
- 150000002576 ketones Chemical class 0.000 description 10
- 239000000203 mixture Substances 0.000 description 10
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 9
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 9
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 9
- 239000003085 diluting agent Substances 0.000 description 9
- 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 8
- 229920000858 Cyclodextrin Polymers 0.000 description 8
- 125000004429 atom Chemical group 0.000 description 8
- 239000002504 physiological saline solution Substances 0.000 description 8
- 125000001424 substituent group Chemical group 0.000 description 8
- 230000000699 topical effect Effects 0.000 description 8
- 229920000954 Polyglycolide Polymers 0.000 description 7
- 239000007864 aqueous solution Substances 0.000 description 7
- 125000004432 carbon atom Chemical group C* 0.000 description 7
- 150000002148 esters Chemical class 0.000 description 7
- XXUPXHKCPIKWLR-JHUOEJJVSA-N isopropyl unoprostone Chemical compound 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 7
- 235000010409 propane-1,2-diol alginate Nutrition 0.000 description 7
- XEYBRNLFEZDVAW-UHFFFAOYSA-N prostaglandin E2 Natural products CCCCCC(O)C=CC1C(O)CC(=O)C1CC=CCCCC(O)=O XEYBRNLFEZDVAW-UHFFFAOYSA-N 0.000 description 7
- 239000000243 solution Substances 0.000 description 7
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 7
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 6
- 239000004215 Carbon black (E152) Substances 0.000 description 6
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- 241000283973 Oryctolagus cuniculus Species 0.000 description 6
- 239000012043 crude product Substances 0.000 description 6
- XEYBRNLFEZDVAW-ARSRFYASSA-N dinoprostone Chemical compound CCCCC[C@H](O)\C=C\[C@H]1[C@H](O)CC(=O)[C@@H]1C\C=C/CCCC(O)=O XEYBRNLFEZDVAW-ARSRFYASSA-N 0.000 description 6
- 229930195733 hydrocarbon Natural products 0.000 description 6
- 230000008961 swelling Effects 0.000 description 6
- 238000010626 work up procedure Methods 0.000 description 6
- 208000001953 Hypotension Diseases 0.000 description 5
- 238000006809 Jones oxidation reaction Methods 0.000 description 5
- 241001465754 Metazoa Species 0.000 description 5
- 150000001721 carbon Chemical group 0.000 description 5
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 5
- 229910052731 fluorine Inorganic materials 0.000 description 5
- 208000021822 hypotensive Diseases 0.000 description 5
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 5
- 230000009467 reduction Effects 0.000 description 5
- 238000006722 reduction reaction Methods 0.000 description 5
- 239000000725 suspension Substances 0.000 description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 4
- 206010023644 Lacrimation increased Diseases 0.000 description 4
- 239000007900 aqueous suspension Substances 0.000 description 4
- 125000002768 hydroxyalkyl group Chemical group 0.000 description 4
- 238000002347 injection Methods 0.000 description 4
- 239000007924 injection Substances 0.000 description 4
- 230000004317 lacrimation Effects 0.000 description 4
- 239000002207 metabolite Substances 0.000 description 4
- PRGUDWLMFLCODA-UHFFFAOYSA-N oxybuprocaine hydrochloride Chemical compound [Cl-].CCCCOC1=CC(C(=O)OCC[NH+](CC)CC)=CC=C1N PRGUDWLMFLCODA-UHFFFAOYSA-N 0.000 description 4
- 229920000136 polysorbate Polymers 0.000 description 4
- 239000003755 preservative agent Substances 0.000 description 4
- 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 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- 108010087367 P-glycoprotein 2 Proteins 0.000 description 3
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-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
- 150000001299 aldehydes Chemical class 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 239000000460 chlorine Substances 0.000 description 3
- 239000000470 constituent Substances 0.000 description 3
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 3
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 3
- 238000010511 deprotection reaction Methods 0.000 description 3
- 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 description 3
- 125000001153 fluoro group Chemical group F* 0.000 description 3
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
- 238000000034 method Methods 0.000 description 3
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 3
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- 238000007254 oxidation reaction Methods 0.000 description 3
- 230000001766 physiological effect Effects 0.000 description 3
- 229950008882 polysorbate Drugs 0.000 description 3
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 3
- HFHDHCJBZVLPGP-UHFFFAOYSA-N schardinger α-dextrin Chemical compound 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 description 3
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- 239000003381 stabilizer Substances 0.000 description 3
- 239000007858 starting material Substances 0.000 description 3
- 238000004659 sterilization and disinfection Methods 0.000 description 3
- KWHXMASXPBOSRE-JKIIOOKNSA-N (2z)-2-[(2r,3s,4s)-4-hydroxy-2-(3-hydroxypropyl)-3,4-dimethyl-3-[(3e,7e)-4,8,12-trimethyltrideca-3,7,11-trienyl]cyclohexylidene]propanal Chemical compound CC(C)=CCC\C(C)=C\CC\C(C)=C\CC[C@@]1(C)[C@H](CCCO)\C(=C(\C)C=O)CC[C@]1(C)O KWHXMASXPBOSRE-JKIIOOKNSA-N 0.000 description 2
- CUJMXIQZWPZMNQ-XYYGWQPLSA-N 13,14-dihydro-15-oxo-prostaglandin E2 Chemical compound CCCCCC(=O)CC[C@H]1[C@H](O)CC(=O)[C@@H]1C\C=C/CCCC(O)=O CUJMXIQZWPZMNQ-XYYGWQPLSA-N 0.000 description 2
- YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
- QFOHBWFCKVYLES-UHFFFAOYSA-N Butylparaben Chemical compound CCCCOC(=O)C1=CC=C(O)C=C1 QFOHBWFCKVYLES-UHFFFAOYSA-N 0.000 description 2
- GAWIXWVDTYZWAW-UHFFFAOYSA-N C[CH]O Chemical group C[CH]O GAWIXWVDTYZWAW-UHFFFAOYSA-N 0.000 description 2
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- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 2
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- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- 206010051625 Conjunctival hyperaemia Diseases 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
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 2
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- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
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- 239000002671 adjuvant Substances 0.000 description 2
- 125000003118 aryl group Chemical group 0.000 description 2
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- 239000002904 solvent Substances 0.000 description 2
- 230000001954 sterilising effect Effects 0.000 description 2
- 229910052717 sulfur Inorganic materials 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
- 239000000080 wetting agent Substances 0.000 description 2
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- 239000011780 sodium chloride Substances 0.000 description 1
- 239000001509 sodium citrate Substances 0.000 description 1
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
- 235000010265 sodium sulphite Nutrition 0.000 description 1
- 239000004334 sorbic acid Substances 0.000 description 1
- 235000010199 sorbic acid Nutrition 0.000 description 1
- 229940075582 sorbic acid Drugs 0.000 description 1
- 208000010110 spontaneous platelet aggregation Diseases 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000008223 sterile water Substances 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 229940124530 sulfonamide Drugs 0.000 description 1
- 150000003456 sulfonamides Chemical class 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 230000009885 systemic effect Effects 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
- 230000001225 therapeutic effect Effects 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 210000003437 trachea Anatomy 0.000 description 1
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 229960000281 trometamol Drugs 0.000 description 1
- 229940099259 vaseline Drugs 0.000 description 1
- 230000024883 vasodilation Effects 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C405/00—Compounds containing a five-membered ring having two side-chains in ortho position to each other, and having oxygen atoms directly attached to the ring in ortho position to one of the side-chains, one side-chain containing, not directly attached to the ring, a carbon atom having three bonds to hetero atoms with at the most one bond to halogen, and the other side-chain having oxygen atoms attached in gamma-position to the ring, e.g. prostaglandins ; Analogues or derivatives thereof
-
- 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
- A61P27/06—Antiglaucoma agents or miotics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Ophthalmology & Optometry (AREA)
- General Chemical & Material Sciences (AREA)
- Epidemiology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Materials For Medical Uses (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP235890/1987 | 1987-09-18 | ||
| JP23589087 | 1987-09-18 | ||
| JP334037/1987 | 1987-12-29 | ||
| JP33403787 | 1987-12-29 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1328075C true CA1328075C (en) | 1994-03-29 |
Family
ID=26532381
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA000577220A Expired - Lifetime CA1328075C (en) | 1987-09-18 | 1988-09-13 | Ocular hypotensive agents |
Country Status (11)
| Country | Link |
|---|---|
| US (1) | US5001153A (forum.php) |
| EP (2) | EP0308135B1 (forum.php) |
| JP (2) | JPH02108A (forum.php) |
| KR (1) | KR930000051B1 (forum.php) |
| AT (2) | ATE82499T1 (forum.php) |
| CA (1) | CA1328075C (forum.php) |
| DE (2) | DE3850676T2 (forum.php) |
| ES (1) | ES2052735T3 (forum.php) |
| GB (1) | GB2209939B (forum.php) |
| GR (1) | GR3006319T3 (forum.php) |
| NZ (1) | NZ226197A (forum.php) |
Families Citing this family (112)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA1322749C (en) * | 1987-01-28 | 1993-10-05 | Ryuzo Ueno | Prostaglandins of the d series, and tranquilizers and soporifics containing the same |
| US5236907A (en) * | 1988-10-01 | 1993-08-17 | R-Tech Ueno Ltd. | Ocular hypotensive agents |
| US6420422B1 (en) | 1987-09-18 | 2002-07-16 | Sucampo Pharmaceuticals, Inc. | Ocular hypotensive agents |
| 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 |
| EP1224934A3 (en) * | 1988-09-06 | 2003-03-26 | Pharmacia AB | Prostaglandin derivatives for the treatment of glaucoma or ocular hypertension |
| US5321128A (en) * | 1988-09-06 | 1994-06-14 | Kabi Pharmacia Ab | Prostaglandin derivatives for the treatment of glaucoma or ocular hypertension |
| US5296504A (en) * | 1988-09-06 | 1994-03-22 | Kabi Pharmacia | Prostaglandin derivatives for the treatment of glaucoma or ocular hypertension |
| US6187813B1 (en) | 1990-04-10 | 2001-02-13 | Pharmacia & Upjohn Aktiebolag | Prostaglandin derivatives for the treatment of glaucoma or ocular hypertension |
| EP1300149A3 (en) * | 1988-09-06 | 2003-05-14 | Pharmacia Aktiebolag | Prostaglandin derivatives for the treatment of glaucoma or ocular hypertension |
| US5194429A (en) * | 1988-10-01 | 1993-03-16 | K.K. Ueno Seiyaku Oyo Kenkyujo | Ocular hypotensive agents |
| ATE111736T1 (de) * | 1988-10-01 | 1994-10-15 | R Tech Ueno Ltd | Okulare hypotensive mittel. |
| US5234954A (en) * | 1989-07-27 | 1993-08-10 | K.K. Ueno Seiyaku Oyo Kenkyujo | Treatment of hyperlipidemia with 15-keto-prostaglandin compounds |
| ATE122563T1 (de) * | 1989-07-27 | 1995-06-15 | Ueno Seiyaku Oyo Kenkyujo Kk | Verwendung von 15-keto-prostansäure-derivaten zur herstellung eines medikaments für die verbesserung der ausscheidung des kaliumions. |
| CA2022372C (en) * | 1989-08-09 | 2000-05-02 | Ryuji Ueno | Improvement of excretion of nonprotein nitrogen into the intestine by prostanoic acid derivatives |
| CA2027814C (en) * | 1989-10-20 | 1996-07-30 | Ryuji Ueno | Treatment of hepatobiliary disease with 15-keto-prostaglandin compounds |
| US5254588A (en) * | 1989-11-22 | 1993-10-19 | Kabushikikaisha Ueno Seiyaku Oyo Kenkyujo | Treatment of pulmonary dysfunction with 15-ketoprostaglandin compounds |
| CA2030345C (en) * | 1989-11-22 | 1998-12-08 | Ryuji Ueno | Use of 15-keto-prostaglandin compound for improvement of encephalic function |
| US5256696A (en) * | 1989-11-22 | 1993-10-26 | Kabushikikaisha Ueno Seiyaku Oyo Kenkyujo | Treatment of cardiac dysfunction with 15-ketoprostaglandin compounds |
| DE69108326T2 (de) * | 1990-03-08 | 1995-07-27 | Shionogi & Co., Ltd., Osaka | 15-deoxyprostaglandinderivat. |
| TW249226B (forum.php) * | 1990-04-04 | 1995-06-11 | Aderk Ueno Kk | |
| CA2041417C (en) * | 1990-05-01 | 2002-05-21 | Ryuji Ueno | Treatment of pancreatic disease with 15-keto-prostaglandin compounds |
| CA2042937C (en) * | 1990-05-22 | 2002-04-30 | Ryuji Ueno | Treatment of ocular hypertension with a synergistic combination |
| ATE117208T1 (de) * | 1990-05-22 | 1995-02-15 | R Tech Ueno Ltd | Behandlung von intraokularem druck mit einer ophthalmischen synergistischen kombination. |
| DK0458588T3 (da) * | 1990-05-22 | 1995-03-13 | R Tech Ueno Ltd | Behandling af okulær hypertension med en synergistisk kombination til okulær administration |
| DE69100171T2 (de) * | 1990-05-22 | 1993-10-28 | Ueno Seiyaku Oyo Kenkyujo Kk | Synergistische Kombination zur ophthalmischen Verwendung. |
| US5175189A (en) * | 1990-05-22 | 1992-12-29 | K.K. Ueno Seiyaku Oyo Kenkyujo | Treatment of ocular hypertension with a synergistic combination for ophthalmic use |
| CA2046069C (en) * | 1990-07-10 | 2002-04-09 | Ryuji Ueno | Treatment of inflammatory diseases with 15-keto-prostaglandin compounds |
| US5270049A (en) * | 1990-11-09 | 1993-12-14 | Allergan, Inc. | 2-decarboxyl-2-aminoalkyl-prostaglandins as ocular hypotensives |
| US5139491A (en) * | 1990-12-06 | 1992-08-18 | Allergan, Inc. | 2-decarboxyl-2-alkoxyalkyl prostaglandins as ocular hypotensives |
| TW210287B (forum.php) * | 1991-03-01 | 1993-08-01 | Kabushikaisha Ueno Seiyaku Oyo Kenkyujo | |
| DK0503887T3 (da) * | 1991-03-14 | 1996-09-16 | R Tech Ueno Ltd | Fremme af sårheling med 15-ketoprostaglandinforbindelser |
| CA2065889C (en) * | 1991-10-02 | 2002-08-27 | Tetsuya Sugiyama | Increasing the choroidal blood flow |
| EP0668076B1 (en) * | 1992-08-26 | 2002-09-04 | Sucampo AG | Stabilization of a prostanoic acid compound |
| FR2707295A1 (fr) * | 1993-06-07 | 1995-01-13 | Rhone Poulenc Agrochimie | Fongicides pyrazoles substitués en position 3 par un hétérocycle. |
| US5510383A (en) * | 1993-08-03 | 1996-04-23 | Alcon Laboratories, Inc. | Use of cloprostenol, fluprostenol and their salts and esters to treat glaucoma and ocular hypertension |
| US6184250B1 (en) | 1993-08-03 | 2001-02-06 | Alcon Laboratories, Inc. | Use of cloprostenol and fluprostenol analogues to treat glaucoma and ocular hypertension |
| US5387608A (en) * | 1993-08-17 | 1995-02-07 | Allergan, Inc. | Cyclopentane(ene) heptanoic or cyclopentane(ene) heptenoic acid, 2-hydrocarbyl sulfonamidomethyl and derivatives thereof as therapeutic agents |
| CA2138181A1 (en) * | 1993-12-15 | 1995-06-16 | Verney L. Sallee | Use of certain prostaglandin analogues to treat glaucoma and ocular hypertension |
| US5807892A (en) * | 1994-09-30 | 1998-09-15 | Alcon Laboratories, Inc. | Use of certain prostaglandin analogues to treat glaucoma and ocular hypertension |
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| US6156785A (en) * | 1998-01-23 | 2000-12-05 | Merck Sharp & Dohme B.V. | Method for increasing oxygen tension in the optic nerve and retina |
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| US4824857A (en) * | 1986-05-16 | 1989-04-25 | Yasumasa Goh | Use of prostaglandin D2 -active substances |
| CA1323364C (en) * | 1987-01-28 | 1993-10-19 | Ryuzo Ueno | Prostaglandins e and anti ulcer agents containing same |
| CA1322749C (en) * | 1987-01-28 | 1993-10-05 | Ryuzo Ueno | Prostaglandins of the d series, and tranquilizers and soporifics containing the same |
| CA1324129C (en) * | 1987-04-30 | 1993-11-09 | Ryuzo Ueno | Prostaglandins of the f series |
| ES2038289T3 (es) * | 1987-05-15 | 1993-07-16 | Kabushiki Kaisha Ueno Seiyaku Oyo Kenkyujo | Utilizacion de 15-ceto-pges para la fabricacion de un medicamento para aumentar la temperatura corporal. |
| JPS6453101A (en) * | 1987-05-25 | 1989-03-01 | Kurashiki Boseki Kk | Equal tilt angle interference type film thickness gauge |
| 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 |
-
1988
- 1988-09-08 DE DE3850676T patent/DE3850676T2/de not_active Expired - Lifetime
- 1988-09-08 EP EP88308299A patent/EP0308135B1/en not_active Expired - Lifetime
- 1988-09-08 AT AT88308299T patent/ATE82499T1/de not_active IP Right Cessation
- 1988-09-08 AT AT91108317T patent/ATE108330T1/de not_active IP Right Cessation
- 1988-09-08 EP EP91108317A patent/EP0455264B1/en not_active Expired - Lifetime
- 1988-09-08 DE DE8888308299T patent/DE3876050T2/de not_active Expired - Lifetime
- 1988-09-08 ES ES88308299T patent/ES2052735T3/es not_active Expired - Lifetime
- 1988-09-08 GB GB8821104A patent/GB2209939B/en not_active Expired - Lifetime
- 1988-09-13 CA CA000577220A patent/CA1328075C/en not_active Expired - Lifetime
- 1988-09-14 JP JP63230469A patent/JPH02108A/ja active Granted
- 1988-09-15 NZ NZ226197A patent/NZ226197A/en unknown
- 1988-09-16 KR KR1019880012030A patent/KR930000051B1/ko not_active Expired - Lifetime
- 1988-09-19 US US07/246,059 patent/US5001153A/en not_active Expired - Lifetime
-
1992
- 1992-11-24 GR GR920402682T patent/GR3006319T3/el unknown
-
1993
- 1993-02-12 JP JP5024099A patent/JP2592204B2/ja not_active Expired - Lifetime
Also Published As
| Publication number | Publication date |
|---|---|
| AU2231388A (en) | 1989-03-23 |
| JPH0680571A (ja) | 1994-03-22 |
| ATE82499T1 (de) | 1992-12-15 |
| DE3876050D1 (de) | 1992-12-24 |
| KR890004707A (ko) | 1989-05-09 |
| EP0455264A3 (en) | 1991-11-27 |
| AU600168B2 (en) | 1990-08-02 |
| ATE108330T1 (de) | 1994-07-15 |
| US5001153A (en) | 1991-03-19 |
| JPH0571567B2 (forum.php) | 1993-10-07 |
| JP2592204B2 (ja) | 1997-03-19 |
| DE3876050T2 (de) | 1993-03-25 |
| EP0308135B1 (en) | 1992-11-19 |
| GB2209939B (en) | 1992-01-02 |
| GB8821104D0 (en) | 1988-10-05 |
| EP0308135A2 (en) | 1989-03-22 |
| DE3850676D1 (de) | 1994-08-18 |
| GB2209939A (en) | 1989-06-01 |
| JPH02108A (ja) | 1990-01-05 |
| GR3006319T3 (forum.php) | 1993-06-21 |
| EP0455264A2 (en) | 1991-11-06 |
| NZ226197A (en) | 1992-02-25 |
| ES2052735T3 (es) | 1994-07-16 |
| EP0308135A3 (en) | 1989-06-14 |
| DE3850676T2 (de) | 1994-11-03 |
| EP0455264B1 (en) | 1994-07-13 |
| KR930000051B1 (ko) | 1993-01-06 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MKEX | Expiry |
Effective date: 20110329 |