NO317155B1 - <omega>-cykloalkyl-prostagladin-E<N>2</N>-derivater - Google Patents
<omega>-cykloalkyl-prostagladin-E<N>2</N>-derivater Download PDFInfo
- Publication number
- NO317155B1 NO317155B1 NO19980442A NO980442A NO317155B1 NO 317155 B1 NO317155 B1 NO 317155B1 NO 19980442 A NO19980442 A NO 19980442A NO 980442 A NO980442 A NO 980442A NO 317155 B1 NO317155 B1 NO 317155B1
- Authority
- NO
- Norway
- Prior art keywords
- dihydroxy
- propano
- dienoic acid
- oxo
- methyl ester
- Prior art date
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- 125000005843 halogen group Chemical group 0.000 claims abstract description 18
- 239000000651 prodrug Substances 0.000 claims abstract description 16
- 229940002612 prodrug Drugs 0.000 claims abstract description 16
- 150000003839 salts Chemical class 0.000 claims abstract description 13
- 229920000858 Cyclodextrin Polymers 0.000 claims abstract description 10
- 125000001424 substituent group Chemical group 0.000 claims abstract description 10
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims abstract description 9
- 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 claims abstract description 9
- 231100000252 nontoxic Toxicity 0.000 claims abstract description 8
- 230000003000 nontoxic effect Effects 0.000 claims abstract description 8
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 7
- 208000010412 Glaucoma Diseases 0.000 claims abstract description 4
- 208000005107 Premature Birth Diseases 0.000 claims abstract description 4
- 206010036590 Premature baby Diseases 0.000 claims abstract description 4
- 208000006673 asthma Diseases 0.000 claims abstract description 4
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims abstract description 4
- 208000026278 immune system disease Diseases 0.000 claims abstract description 4
- 230000016273 neuron death Effects 0.000 claims abstract description 4
- 201000001119 neuropathy Diseases 0.000 claims abstract description 4
- 230000007823 neuropathy Effects 0.000 claims abstract description 4
- 208000033808 peripheral neuropathy Diseases 0.000 claims abstract description 4
- 206010067125 Liver injury Diseases 0.000 claims abstract description 3
- 230000002159 abnormal effect Effects 0.000 claims abstract description 3
- 231100000234 hepatic damage Toxicity 0.000 claims abstract description 3
- 230000008818 liver damage Effects 0.000 claims abstract description 3
- 230000011164 ossification Effects 0.000 claims abstract description 3
- 230000002265 prevention Effects 0.000 claims abstract description 3
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims abstract description 3
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims abstract 4
- 125000004209 (C1-C8) alkyl group Chemical group 0.000 claims abstract 3
- 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims abstract 2
- 150000001875 compounds Chemical group 0.000 claims description 249
- 239000000203 mixture Substances 0.000 claims description 94
- 239000002253 acid Substances 0.000 claims description 79
- 150000004702 methyl esters Chemical class 0.000 claims description 68
- 238000000034 method Methods 0.000 claims description 52
- -1 (5Z,11a,16RS)-11,16-dihydroxy-9-oxo-17,17-propanoprosta-5-en-13-acetic acid methyl ester Chemical compound 0.000 claims description 23
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 20
- 230000002378 acidificating effect Effects 0.000 claims description 17
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 15
- 125000006239 protecting group Chemical group 0.000 claims description 11
- 238000004519 manufacturing process Methods 0.000 claims description 8
- 238000002360 preparation method Methods 0.000 claims description 8
- 125000003545 alkoxy group Chemical group 0.000 claims description 6
- 125000000217 alkyl group Chemical group 0.000 claims description 5
- 108090000790 Enzymes Proteins 0.000 claims description 4
- 102000004190 Enzymes Human genes 0.000 claims description 4
- 230000009435 amidation Effects 0.000 claims description 4
- 238000007112 amidation reaction Methods 0.000 claims description 4
- 230000002207 retinal effect Effects 0.000 claims description 3
- 239000000126 substance Substances 0.000 claims description 3
- 206010000234 Abortion spontaneous Diseases 0.000 claims description 2
- 239000011248 coating agent Substances 0.000 claims description 2
- 238000000576 coating method Methods 0.000 claims description 2
- 239000003814 drug Substances 0.000 claims description 2
- 208000015994 miscarriage Diseases 0.000 claims description 2
- 239000008194 pharmaceutical composition Substances 0.000 claims description 2
- 208000000995 spontaneous abortion Diseases 0.000 claims description 2
- 230000003301 hydrolyzing effect Effects 0.000 claims 3
- GJBNXBYGZPKYOY-YHCAYNLDSA-N (z)-7-[(1r,2r)-2-[(e)-4-hydroxy-4-(1-propylcyclobutyl)but-1-enyl]-5-oxocyclopentyl]hept-5-enoic acid Chemical compound C(\[C@@H]1[C@H](C(=O)CC1)C\C=C/CCCC(O)=O)=C/CC(O)C1(CCC)CCC1 GJBNXBYGZPKYOY-YHCAYNLDSA-N 0.000 claims 1
- ANJZWTITKJFTLO-UJDFSMTGSA-N (z)-7-[(1r,2r,3r)-2-[(e)-4-(1-but-2-ynylcyclobutyl)-4-hydroxybut-1-enyl]-3-hydroxy-5-oxocyclopentyl]hept-5-enoic acid Chemical compound C(\[C@@H]1[C@H](C(=O)C[C@H]1O)C\C=C/CCCC(O)=O)=C/CC(O)C1(CC#CC)CCC1 ANJZWTITKJFTLO-UJDFSMTGSA-N 0.000 claims 1
- NJISZWJIQGBZIG-QIDWXHFYSA-N (z)-7-[(1r,2r,3r)-2-[(e)-4-[1-(3-fluoropropyl)cyclobutyl]-4-hydroxybut-1-enyl]-3-hydroxy-5-oxocyclopentyl]hept-5-enoic acid Chemical compound C1CCC1(CCCF)C(O)C\C=C\[C@H]1[C@H](O)CC(=O)[C@@H]1C\C=C/CCCC(O)=O NJISZWJIQGBZIG-QIDWXHFYSA-N 0.000 claims 1
- VIDKVRRYTPQMNS-CKRBMUGPSA-N (z)-7-[(1r,2r,3r)-2-[(e)-4-[1-(cyclopropylmethyl)cyclobutyl]-4-hydroxybut-1-enyl]-3-hydroxy-5-oxocyclopentyl]hept-5-enoic acid Chemical compound C1CCC1(CC1CC1)C(O)C\C=C\[C@H]1[C@H](O)CC(=O)[C@@H]1C\C=C/CCCC(O)=O VIDKVRRYTPQMNS-CKRBMUGPSA-N 0.000 claims 1
- JEBWPCNHENRTRM-PHDOPTCZSA-N (z)-7-[(1r,2r,3r)-3-hydroxy-2-[(e)-4-hydroxy-4-(1-prop-2-enylcyclobutyl)but-1-enyl]-5-oxocyclopentyl]hept-5-enoic acid Chemical compound C1CCC1(CC=C)C(O)C\C=C\[C@H]1[C@H](O)CC(=O)[C@@H]1C\C=C/CCCC(O)=O JEBWPCNHENRTRM-PHDOPTCZSA-N 0.000 claims 1
- ZEPZTXZNRWIUEX-PHDOPTCZSA-N (z)-7-[(1r,2r,3r)-3-hydroxy-2-[(e)-4-hydroxy-4-(1-propylcyclobutyl)but-1-enyl]-5-oxocyclopentyl]hept-5-enamide Chemical compound C(\[C@@H]1[C@H](C(=O)C[C@H]1O)C\C=C/CCCC(N)=O)=C/CC(O)C1(CCC)CCC1 ZEPZTXZNRWIUEX-PHDOPTCZSA-N 0.000 claims 1
- HJVBXPOYFHMZAS-PHDOPTCZSA-N (z)-7-[(1r,2r,3r)-3-hydroxy-2-[(e)-4-hydroxy-4-(1-propylcyclobutyl)but-1-enyl]-5-oxocyclopentyl]hept-5-enoic acid Chemical compound C(\[C@@H]1[C@H](C(=O)C[C@H]1O)C\C=C/CCCC(O)=O)=C/CC(O)C1(CCC)CCC1 HJVBXPOYFHMZAS-PHDOPTCZSA-N 0.000 claims 1
- VOMWVPBXPITBHJ-KDUQRRADSA-N (z)-7-[(1r,2r,3r)-3-hydroxy-2-[(e)-4-hydroxy-4-(1-propylcyclohexyl)but-1-enyl]-5-oxocyclopentyl]hept-5-enoic acid Chemical compound C(\[C@@H]1[C@H](C(=O)C[C@H]1O)C\C=C/CCCC(O)=O)=C/CC(O)C1(CCC)CCCCC1 VOMWVPBXPITBHJ-KDUQRRADSA-N 0.000 claims 1
- CGVFVYJKFYSUMB-GNZOUYFFSA-N (z)-7-[(1r,2r,3r)-3-hydroxy-2-[(e)-4-hydroxy-4-(1-propylcyclopentyl)but-1-enyl]-5-oxocyclopentyl]hept-5-enoic acid Chemical compound C(\[C@@H]1[C@H](C(=O)C[C@H]1O)C\C=C/CCCC(O)=O)=C/CC(O)C1(CCC)CCCC1 CGVFVYJKFYSUMB-GNZOUYFFSA-N 0.000 claims 1
- SREKTZDGSCHVQR-HNXWEVKXSA-N (z)-7-[(1r,2r,3r)-3-hydroxy-2-[(e)-4-hydroxy-4-[1-(2-methylpropyl)cyclobutyl]but-1-enyl]-5-oxocyclopentyl]hept-5-enoic acid Chemical compound C(\[C@@H]1[C@H](C(=O)C[C@H]1O)C\C=C/CCCC(O)=O)=C/CC(O)C1(CC(C)C)CCC1 SREKTZDGSCHVQR-HNXWEVKXSA-N 0.000 claims 1
- WMUJVJFFBXITLC-NGLSELPESA-N (z)-7-[(1r,2r,3r)-3-hydroxy-2-[(e)-4-hydroxy-4-[1-(3-methoxypropyl)cyclobutyl]but-1-enyl]-5-oxocyclopentyl]hept-5-enoic acid Chemical compound C(\[C@@H]1[C@H](C(=O)C[C@H]1O)C\C=C/CCCC(O)=O)=C/CC(O)C1(CCCOC)CCC1 WMUJVJFFBXITLC-NGLSELPESA-N 0.000 claims 1
- HJVBXPOYFHMZAS-BJUNZTGTSA-N (z)-7-[(1r,2r,3r)-3-hydroxy-2-[(z)-4-hydroxy-4-(1-propylcyclobutyl)but-1-enyl]-5-oxocyclopentyl]hept-5-enoic acid Chemical compound C(/[C@@H]1[C@H](C(=O)C[C@H]1O)C\C=C/CCCC(O)=O)=C/CC(O)C1(CCC)CCC1 HJVBXPOYFHMZAS-BJUNZTGTSA-N 0.000 claims 1
- JCXJVPUVTGWSNB-UHFFFAOYSA-N Nitrogen dioxide Chemical class O=[N]=O JCXJVPUVTGWSNB-UHFFFAOYSA-N 0.000 claims 1
- YZCKVEUIGOORGS-IGMARMGPSA-N Protium Chemical compound [1H] YZCKVEUIGOORGS-IGMARMGPSA-N 0.000 claims 1
- 229940079593 drug Drugs 0.000 claims 1
- JZKYSOIPVAUXAL-LGKAVXRHSA-N methyl (Z)-7-[(1R,2R,3R,5S)-5-chloro-3-hydroxy-2-[(E)-4-hydroxy-4-(1-propylcyclobutyl)but-1-enyl]cyclopentyl]hept-5-enoate Chemical compound C(\[C@@H]1[C@H]([C@@H](Cl)C[C@H]1O)C\C=C/CCCC(=O)OC)=C/CC(O)C1(CCC)CCC1 JZKYSOIPVAUXAL-LGKAVXRHSA-N 0.000 claims 1
- ZZPQECYGQBWMKH-KFQNNBJWSA-N methyl (z)-7-[(1r,2r)-2-[(e)-4-hydroxy-4-(1-propylcyclobutyl)but-1-enyl]-5-oxocyclopentyl]hept-5-enoate Chemical compound C(\[C@@H]1[C@H](C(=O)CC1)C\C=C/CCCC(=O)OC)=C/CC(O)C1(CCC)CCC1 ZZPQECYGQBWMKH-KFQNNBJWSA-N 0.000 claims 1
- VELQKHIUWBLFBK-YSHAJIKCSA-N methyl (z)-7-[(1r,2r,3r)-2-[(e)-4-(1-butylcyclobutyl)-4-hydroxybut-1-enyl]-3-hydroxy-5-oxocyclopentyl]hept-5-enoate Chemical compound C(\[C@@H]1[C@H](C(=O)C[C@H]1O)C\C=C/CCCC(=O)OC)=C/CC(O)C1(CCCC)CCC1 VELQKHIUWBLFBK-YSHAJIKCSA-N 0.000 claims 1
- REQHWNMIQWFCKO-UKCDNCSVSA-N methyl (z)-7-[(1r,2r,3r)-3-hydroxy-2-[(e)-4-hydroxy-4-(1-pentylcyclobutyl)but-1-enyl]-5-oxocyclopentyl]hept-5-enoate Chemical compound C(\[C@@H]1[C@H](C(=O)C[C@H]1O)C\C=C/CCCC(=O)OC)=C/CC(O)C1(CCCCC)CCC1 REQHWNMIQWFCKO-UKCDNCSVSA-N 0.000 claims 1
- HEVOGQQMSVWWNW-UJDFSMTGSA-N methyl (z)-7-[(1r,2r,3r)-3-hydroxy-2-[(e)-4-hydroxy-4-(1-prop-2-enylcyclobutyl)but-1-enyl]-5-oxocyclopentyl]hept-5-enoate Chemical compound O[C@@H]1CC(=O)[C@H](C\C=C/CCCC(=O)OC)[C@H]1\C=C\CC(O)C1(CC=C)CCC1 HEVOGQQMSVWWNW-UJDFSMTGSA-N 0.000 claims 1
- OAAFFLHKOHBPDW-MIWOFANNSA-N methyl (z)-7-[(1r,2r,3r)-3-hydroxy-2-[(e)-4-hydroxy-4-(1-propylcyclohexyl)but-1-enyl]-5-oxocyclopentyl]hept-5-enoate Chemical compound C(\[C@@H]1[C@H](C(=O)C[C@H]1O)C\C=C/CCCC(=O)OC)=C/CC(O)C1(CCC)CCCCC1 OAAFFLHKOHBPDW-MIWOFANNSA-N 0.000 claims 1
- BNOOGVQJVBHGNE-HKCRBYSZSA-N methyl (z)-7-[(1r,2r,3r)-3-hydroxy-2-[4-hydroxy-4-(1-propylcyclobutyl)butyl]-5-oxocyclopentyl]hept-5-enoate Chemical compound C([C@@H]1[C@H](C(=O)C[C@H]1O)C\C=C/CCCC(=O)OC)CCC(O)C1(CCC)CCC1 BNOOGVQJVBHGNE-HKCRBYSZSA-N 0.000 claims 1
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 abstract description 4
- 208000023275 Autoimmune disease Diseases 0.000 abstract description 3
- 210000000056 organ Anatomy 0.000 abstract description 3
- 206010000210 abortion Diseases 0.000 abstract description 2
- 231100000176 abortion Toxicity 0.000 abstract description 2
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 abstract description 2
- 125000004648 C2-C8 alkenyl group Chemical group 0.000 abstract 2
- 125000004649 C2-C8 alkynyl group Chemical group 0.000 abstract 2
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 abstract 1
- 125000004043 oxo group Chemical group O=* 0.000 abstract 1
- 210000001525 retina Anatomy 0.000 abstract 1
- 238000002054 transplantation Methods 0.000 abstract 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 600
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 541
- 229910052739 hydrogen Inorganic materials 0.000 description 424
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 162
- 238000004809 thin layer chromatography Methods 0.000 description 162
- 239000007864 aqueous solution Substances 0.000 description 83
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 72
- 239000000243 solution Substances 0.000 description 64
- 229920006395 saturated elastomer Polymers 0.000 description 62
- 238000006243 chemical reaction Methods 0.000 description 54
- 239000011541 reaction mixture Substances 0.000 description 48
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 46
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 40
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 39
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 37
- 239000000741 silica gel Substances 0.000 description 37
- 229910002027 silica gel Inorganic materials 0.000 description 37
- 239000011780 sodium chloride Substances 0.000 description 36
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 35
- 239000000284 extract Substances 0.000 description 34
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 33
- 238000004440 column chromatography Methods 0.000 description 32
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 30
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 30
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 25
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 20
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 19
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 16
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 15
- 229910052786 argon Inorganic materials 0.000 description 15
- 239000012298 atmosphere Substances 0.000 description 15
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 12
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 12
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 12
- 102000005962 receptors Human genes 0.000 description 11
- 108020003175 receptors Proteins 0.000 description 11
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 11
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 10
- 102100024448 Prostaglandin E2 receptor EP2 subtype Human genes 0.000 description 10
- 230000007062 hydrolysis Effects 0.000 description 10
- 238000006460 hydrolysis reaction Methods 0.000 description 10
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 9
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- 235000019270 ammonium chloride Nutrition 0.000 description 8
- 239000012230 colorless oil Substances 0.000 description 8
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 7
- 230000027455 binding Effects 0.000 description 7
- OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 7
- 239000003960 organic solvent Substances 0.000 description 7
- 239000000725 suspension Substances 0.000 description 7
- OISVCGZHLKNMSJ-UHFFFAOYSA-N 2,6-dimethylpyridine Chemical compound CC1=CC=CC(C)=N1 OISVCGZHLKNMSJ-UHFFFAOYSA-N 0.000 description 6
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 6
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
- KRHYYFGTRYWZRS-UHFFFAOYSA-N Fluorane Chemical compound F KRHYYFGTRYWZRS-UHFFFAOYSA-N 0.000 description 6
- 125000004432 carbon atom Chemical group C* 0.000 description 6
- 229960002986 dinoprostone Drugs 0.000 description 6
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 6
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 6
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 6
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 6
- 235000017557 sodium bicarbonate Nutrition 0.000 description 6
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 6
- OZAIFHULBGXAKX-UHFFFAOYSA-N 2-(2-cyanopropan-2-yldiazenyl)-2-methylpropanenitrile Chemical compound N#CC(C)(C)N=NC(C)(C)C#N OZAIFHULBGXAKX-UHFFFAOYSA-N 0.000 description 5
- 239000000872 buffer Substances 0.000 description 5
- 239000003795 chemical substances by application Substances 0.000 description 5
- 230000000694 effects Effects 0.000 description 5
- 239000003701 inert diluent Substances 0.000 description 5
- 238000007911 parenteral administration Methods 0.000 description 5
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 4
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 4
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 4
- YZXBAPSDXZZRGB-DOFZRALJSA-N arachidonic acid Chemical compound CCCCC\C=C/C\C=C/C\C=C/C\C=C/CCCC(O)=O YZXBAPSDXZZRGB-DOFZRALJSA-N 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
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 4
- 238000001816 cooling Methods 0.000 description 4
- 125000000753 cycloalkyl group Chemical group 0.000 description 4
- BGTOWKSIORTVQH-UHFFFAOYSA-N cyclopentanone Chemical compound O=C1CCCC1 BGTOWKSIORTVQH-UHFFFAOYSA-N 0.000 description 4
- CSJLBAMHHLJAAS-UHFFFAOYSA-N diethylaminosulfur trifluoride Chemical compound CCN(CC)S(F)(F)F CSJLBAMHHLJAAS-UHFFFAOYSA-N 0.000 description 4
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 4
- 239000007924 injection Substances 0.000 description 4
- 238000002347 injection Methods 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- 229910052744 lithium Inorganic materials 0.000 description 4
- UBJFKNSINUCEAL-UHFFFAOYSA-N lithium;2-methylpropane Chemical compound [Li+].C[C-](C)C UBJFKNSINUCEAL-UHFFFAOYSA-N 0.000 description 4
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- XNGIFLGASWRNHJ-UHFFFAOYSA-L phthalate(2-) Chemical compound [O-]C(=O)C1=CC=CC=C1C([O-])=O XNGIFLGASWRNHJ-UHFFFAOYSA-L 0.000 description 1
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- QEMXHQIAXOOASZ-UHFFFAOYSA-N tetramethylammonium Chemical compound C[N+](C)(C)C QEMXHQIAXOOASZ-UHFFFAOYSA-N 0.000 description 1
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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
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (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)
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP3549997 | 1997-02-04 | ||
JP31916997 | 1997-11-06 |
Publications (3)
Publication Number | Publication Date |
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NO980442D0 NO980442D0 (no) | 1998-02-02 |
NO980442L NO980442L (no) | 1998-08-05 |
NO317155B1 true NO317155B1 (no) | 2004-08-30 |
Family
ID=26374500
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
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NO19980442A NO317155B1 (no) | 1997-02-04 | 1998-02-02 | <omega>-cykloalkyl-prostagladin-E<N>2</N>-derivater |
Country Status (13)
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US (3) | US6110969A (pt) |
EP (1) | EP0860430B1 (pt) |
KR (1) | KR100573535B1 (pt) |
AT (1) | ATE219054T1 (pt) |
AU (1) | AU736271B2 (pt) |
CA (1) | CA2228828A1 (pt) |
DE (1) | DE69805874T2 (pt) |
DK (1) | DK0860430T3 (pt) |
ES (1) | ES2178808T3 (pt) |
HU (1) | HUP9800208A3 (pt) |
NO (1) | NO317155B1 (pt) |
PT (1) | PT860430E (pt) |
TW (1) | TW581756B (pt) |
Families Citing this family (52)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
ATE390917T1 (de) | 1996-12-20 | 2008-04-15 | Pfizer | Prävention und behandlung von skeletterkrankungen mit ep2 subtyp selektiven prostaglandin e2 agonisten |
US6235780B1 (en) * | 1998-07-21 | 2001-05-22 | Ono Pharmaceutical Co., Ltd. | ω-cycloalkyl-prostaglandin E1 derivatives |
JP4834224B2 (ja) | 1999-03-05 | 2011-12-14 | デューク ユニバーシティ | C16不飽和fp−選択的プロスタグランジン類縁体 |
US20020172693A1 (en) | 2000-03-31 | 2002-11-21 | Delong Michell Anthony | Compositions and methods for treating hair loss using non-naturally occurring prostaglandins |
US20020013294A1 (en) | 2000-03-31 | 2002-01-31 | Delong Mitchell Anthony | Cosmetic and pharmaceutical compositions and methods using 2-decarboxy-2-phosphinico derivatives |
US20020037914A1 (en) * | 2000-03-31 | 2002-03-28 | Delong Mitchell Anthony | Compositions and methods for treating hair loss using C16-C20 aromatic tetrahydro prostaglandins |
WO2002009717A1 (fr) * | 2000-07-31 | 2002-02-07 | Ono Pharmaceutical Co., Ltd. | Remedes contre la dyserection contenant des derives de prostaglandine comme principe actif |
US6410591B1 (en) * | 2001-05-08 | 2002-06-25 | Allergan Sales, Inc. | 3,7 or 3 and 7 thia or oxa prostanoic acid derivatives as agents for lowering intraocular pressure |
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US20030027853A1 (en) | 2001-06-14 | 2003-02-06 | Allergan Sales, Inc. | 3, 7or3 and 7 thia or oxa prostanoic acid derivatives as agents for lowering intraocular pressure |
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MXPA04004371A (es) * | 2002-08-09 | 2004-08-13 | Taisho Pharmaceutical Co Ltd | Agente antipruritico. |
US7737182B2 (en) | 2002-08-09 | 2010-06-15 | Taisho Pharmaceutical Co., Ltd. | Pharmaceuticals for xerosis |
ES2393321T3 (es) * | 2002-10-10 | 2012-12-20 | Ono Pharmaceutical Co., Ltd. | Promotores de la producción de factores de reparación endógenos |
WO2004043471A1 (ja) * | 2002-11-13 | 2004-05-27 | Taisho Pharmaceutical Co., Ltd. | 鎮痒剤 |
WO2004073591A2 (en) * | 2003-02-24 | 2004-09-02 | Bayer Healthcare Ag | Diagnostics and therapeutics for diseases associated with g-protein coupled receptor prostaglandin e2 ep2 (prostaglandin e2 ep2) |
JPWO2004089411A1 (ja) * | 2003-04-03 | 2006-07-06 | 小野薬品工業株式会社 | 脊柱管狭窄症治療剤 |
US20070270489A1 (en) * | 2003-07-25 | 2007-11-22 | Ono Pharmaceutical Co., Ltd. | Remedy for Cartilage-Related Diseases |
JP4893999B2 (ja) * | 2004-10-22 | 2012-03-07 | 小野薬品工業株式会社 | 吸入用医薬組成物 |
AR053710A1 (es) * | 2005-04-11 | 2007-05-16 | Xenon Pharmaceuticals Inc | Compuestos espiroheterociclicos y sus usos como agentes terapeuticos |
MY144968A (en) * | 2005-04-11 | 2011-11-30 | Xenon Pharmaceuticals Inc | Spiro-oxindole compounds and their uses as therapeutic agents |
RU2420316C2 (ru) | 2005-06-03 | 2011-06-10 | Оно Фармасьютикал Ко., Лтд. | Агент для регенерации и/или защиты нервов |
US7563924B2 (en) * | 2005-11-21 | 2009-07-21 | Schering Aktiengesellschaft | 9-chloro-15-deoxyprostaglandin derivatives, process for their preparation and their use as medicaments |
US7737145B2 (en) | 2005-12-29 | 2010-06-15 | Estrellita Pharmaceuticals, Llc | Diamine derivatives as inhibitors of leukotriene A4 hydrolase |
AU2007307638A1 (en) * | 2006-10-12 | 2008-04-17 | Xenon Pharmaceuticals Inc. | Spiro (furo [3, 2-C] pyridine-3-3 ' -indol) -2' (1'H)-one derivatives and related compounds for the treatment of sodium-channel mediated diseases, such as pain |
ATE545416T1 (de) | 2006-10-12 | 2012-03-15 | Xenon Pharmaceuticals Inc | Verwendung von spiro-oxindol-verbindungen als therapeutika |
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US7960378B2 (en) * | 2008-03-18 | 2011-06-14 | Allergan, Inc. | Therapeutic compounds |
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CA2741024A1 (en) * | 2008-10-17 | 2010-04-22 | Xenon Pharmaceuticals Inc. | Spiro-oxindole compounds and their use as therapeutic agents |
CA2741029A1 (en) | 2008-10-17 | 2010-04-22 | Xenon Pharmaceuticals Inc. | Spiro-oxindole compounds and their use as therapeutic agents |
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 |
AR077252A1 (es) * | 2009-06-29 | 2011-08-10 | Xenon Pharmaceuticals Inc | Enantiomeros de compuestos de espirooxindol y sus usos como agentes terapeuticos |
US20110086899A1 (en) * | 2009-10-14 | 2011-04-14 | Xenon Pharmaceuticals Inc. | Pharmaceutical compositions for oral administration |
NZ712378A (en) | 2009-10-14 | 2017-05-26 | Xenon Pharmaceuticals Inc | Synthetic methods for spiro-oxindole compounds |
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AU2012299218A1 (en) | 2011-08-19 | 2014-02-20 | Merck Sharp & Dohme Corp. | Crystal forms of a HCV protease inhibitor |
RU2474426C1 (ru) * | 2011-12-26 | 2013-02-10 | Учреждение Российской академии наук Институт биоорганической химии им. академиков М.М. Шемякина и Ю.А. Овчинникова РАН | Простамиды и их аналоги, обладающие нейрозащитным действием |
CA2869547A1 (en) | 2012-04-12 | 2013-10-17 | Xenon Pharmaceuticals Inc. | Asymmetric syntheses for spiro-oxindole compounds useful as therapeutic agents |
JP6400479B2 (ja) | 2012-10-29 | 2018-10-03 | 株式会社カルディオ | 肺疾患特異的治療剤 |
CA2906035A1 (en) | 2013-03-14 | 2014-09-25 | Celtaxsys, Inc. | Inhibitors of leukotriene a4 hydrolase |
EP2818484A1 (en) | 2013-06-28 | 2014-12-31 | Universitat Autònoma de Barcelona | Synergistic combination of an anti-IgE antibody and an EP2 receptor agonist |
WO2015056504A1 (ja) | 2013-10-15 | 2015-04-23 | 小野薬品工業株式会社 | 薬剤溶出性ステントグラフト |
TW201636017A (zh) | 2015-02-05 | 2016-10-16 | 梯瓦製藥國際有限責任公司 | 以螺吲哚酮化合物之局部調配物治療帶狀疱疹後遺神經痛之方法 |
US10100060B2 (en) | 2016-06-16 | 2018-10-16 | Xenon Pharmaceuticals Inc. | Asymmetric synthesis of funapide |
CA3045954A1 (en) | 2016-12-09 | 2018-06-14 | Celtaxsys, Inc. | Monamine and monoamine derivatives as inhibitors of leukotriene a4 hydrolase |
EP3551608A1 (en) | 2016-12-09 | 2019-10-16 | Celtaxsys Inc. | Pendant amines and derivatives as inhibitors of leukotriene a4 hydrolase |
WO2018107153A1 (en) | 2016-12-09 | 2018-06-14 | Celtaxsys, Inc. | Inhibitors of leukotriene a4 hydrolase |
Family Cites Families (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4061670A (en) * | 1976-07-19 | 1977-12-06 | American Cyanamid Company | 15-Deoxy-16-hydroxy-16-vinyl and cyclopropyl substituted prostanoic acids and congeners |
US4132738A (en) * | 1978-02-23 | 1979-01-02 | Miles Laboratories, Inc. | Preparation of 15-deoxy-16-hydroxyprostaglandins |
US4336404A (en) * | 1979-05-14 | 1982-06-22 | Miles Laboratories, Inc. | 1-Acyloxy-15-deoxy-16-hydroxy-analogs of prostaglandin E1 |
US4363817A (en) * | 1981-08-27 | 1982-12-14 | Miles Laboratories, Inc. | Enol acylate analogs of E1 and E2 prostaglandins |
US5698598A (en) * | 1995-08-04 | 1997-12-16 | Allergan | EP2 -receptor agonists as agents for lowering intraocular pressure |
-
1998
- 1998-02-02 NO NO19980442A patent/NO317155B1/no unknown
- 1998-02-03 KR KR1019980002882A patent/KR100573535B1/ko not_active IP Right Cessation
- 1998-02-03 PT PT98300769T patent/PT860430E/pt unknown
- 1998-02-03 EP EP98300769A patent/EP0860430B1/en not_active Expired - Lifetime
- 1998-02-03 DK DK98300769T patent/DK0860430T3/da active
- 1998-02-03 AT AT98300769T patent/ATE219054T1/de not_active IP Right Cessation
- 1998-02-03 HU HU9800208A patent/HUP9800208A3/hu unknown
- 1998-02-03 DE DE69805874T patent/DE69805874T2/de not_active Expired - Lifetime
- 1998-02-03 TW TW087101279A patent/TW581756B/zh not_active IP Right Cessation
- 1998-02-03 ES ES98300769T patent/ES2178808T3/es not_active Expired - Lifetime
- 1998-02-04 US US09/018,565 patent/US6110969A/en not_active Expired - Lifetime
- 1998-02-04 CA CA002228828A patent/CA2228828A1/en not_active Abandoned
- 1998-02-04 AU AU52892/98A patent/AU736271B2/en not_active Ceased
-
2000
- 2000-05-12 US US09/570,728 patent/US6576785B1/en not_active Expired - Fee Related
-
2002
- 2002-09-11 US US10/238,623 patent/US20030186939A1/en not_active Abandoned
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EP0860430A3 (en) | 1999-06-23 |
TW581756B (en) | 2004-04-01 |
DK0860430T3 (da) | 2002-09-09 |
EP0860430A2 (en) | 1998-08-26 |
KR100573535B1 (ko) | 2006-12-15 |
HUP9800208A3 (en) | 2000-04-28 |
HU9800208D0 (en) | 1998-03-30 |
NO980442L (no) | 1998-08-05 |
EP0860430B1 (en) | 2002-06-12 |
PT860430E (pt) | 2002-11-29 |
DE69805874D1 (de) | 2002-07-18 |
CA2228828A1 (en) | 1998-08-04 |
AU5289298A (en) | 1998-08-06 |
HUP9800208A2 (hu) | 1998-09-28 |
US20030186939A1 (en) | 2003-10-02 |
US6576785B1 (en) | 2003-06-10 |
NO980442D0 (no) | 1998-02-02 |
US6110969A (en) | 2000-08-29 |
KR19980071021A (ko) | 1998-10-26 |
DE69805874T2 (de) | 2002-12-19 |
AU736271B2 (en) | 2001-07-26 |
ES2178808T3 (es) | 2003-01-01 |
ATE219054T1 (de) | 2002-06-15 |
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