NO309475B1 - Tiazolidinonforbindelser og terapeutisk eller forhindrende middel mot angina pectoris omfattende forbindelsene som aktiv bestanddel - Google Patents
Tiazolidinonforbindelser og terapeutisk eller forhindrende middel mot angina pectoris omfattende forbindelsene som aktiv bestanddel Download PDFInfo
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- NO309475B1 NO309475B1 NO972731A NO972731A NO309475B1 NO 309475 B1 NO309475 B1 NO 309475B1 NO 972731 A NO972731 A NO 972731A NO 972731 A NO972731 A NO 972731A NO 309475 B1 NO309475 B1 NO 309475B1
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- 150000001875 compounds Chemical class 0.000 title claims abstract description 300
- 206010002383 Angina Pectoris Diseases 0.000 title claims abstract description 12
- 230000001225 therapeutic effect Effects 0.000 title abstract 2
- 239000004480 active ingredient Substances 0.000 title description 2
- 230000000069 prophylactic effect Effects 0.000 title 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 43
- 150000003839 salts Chemical class 0.000 claims abstract description 38
- 229910052717 sulfur Inorganic materials 0.000 claims abstract description 10
- 125000004434 sulfur atom Chemical group 0.000 claims abstract description 10
- -1 3-nitroxymethylcyclopentyl group Chemical group 0.000 claims description 135
- 239000000203 mixture Substances 0.000 claims description 135
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 12
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 claims description 9
- 239000003814 drug Substances 0.000 claims description 8
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 6
- 238000002360 preparation method Methods 0.000 claims description 6
- 125000000816 ethylene group Chemical group [H]C([H])([*:1])C([H])([H])[*:2] 0.000 claims description 4
- 239000003085 diluting agent Substances 0.000 claims description 3
- JCUYOQLDNMDHJI-UHFFFAOYSA-N 2-[4-[[(2-oxo-1,3-thiazolidine-4-carbonyl)amino]methyl]cyclohexyl]ethyl nitrate Chemical compound C1CC(CCO[N+](=O)[O-])CCC1CNC(=O)C1NC(=O)SC1 JCUYOQLDNMDHJI-UHFFFAOYSA-N 0.000 claims description 2
- MBDPKTSSWTYUET-UHFFFAOYSA-N 3-[4-[2-[(2-oxo-1,3-thiazolidine-4-carbonyl)amino]ethyl]cyclohexyl]propyl nitrate Chemical compound O([N+](=O)[O-])CCCC1CCC(CC1)CCNC(=O)C1NC(SC1)=O MBDPKTSSWTYUET-UHFFFAOYSA-N 0.000 claims description 2
- FBODSPJJULEPQM-UHFFFAOYSA-N 3-[4-[[(2-oxo-1,3-thiazolidine-4-carbonyl)amino]methyl]cyclohexyl]propyl nitrate Chemical compound C1CC(CCCO[N+](=O)[O-])CCC1CNC(=O)C1NC(=O)SC1 FBODSPJJULEPQM-UHFFFAOYSA-N 0.000 claims description 2
- SXPPREPWJICSIJ-UHFFFAOYSA-N C1CC(CO[N+](=O)[O-])CCC1CCNC(=O)C1C(CC=2C=CC=CC=2)SC(=O)N1 Chemical compound C1CC(CO[N+](=O)[O-])CCC1CCNC(=O)C1C(CC=2C=CC=CC=2)SC(=O)N1 SXPPREPWJICSIJ-UHFFFAOYSA-N 0.000 claims description 2
- WMJNLZSDIGFFNC-UHFFFAOYSA-N CC1SC(=O)NC1C(=O)NCCC1CCC(CO[N+]([O-])=O)CC1 Chemical compound CC1SC(=O)NC1C(=O)NCCC1CCC(CO[N+]([O-])=O)CC1 WMJNLZSDIGFFNC-UHFFFAOYSA-N 0.000 claims description 2
- XPCKBWHSMGWVLY-UHFFFAOYSA-N [4-[[(2-oxo-1,3-thiazolidine-4-carbonyl)amino]methyl]cyclohexyl]methyl nitrate Chemical compound C1CC(CO[N+](=O)[O-])CCC1CNC(=O)C1NC(=O)SC1 XPCKBWHSMGWVLY-UHFFFAOYSA-N 0.000 claims description 2
- HIKGAUSDLODDEE-UHFFFAOYSA-N [4-[[(5-benzyl-2-oxo-1,3-thiazolidine-4-carbonyl)amino]methyl]cyclohexyl]methyl nitrate Chemical compound O([N+](=O)[O-])CC1CCC(CC1)CNC(=O)C1NC(SC1CC1=CC=CC=C1)=O HIKGAUSDLODDEE-UHFFFAOYSA-N 0.000 claims description 2
- XESZSJIJMJQGSY-UHFFFAOYSA-N [4-[[(5-methyl-2-oxo-1,3-thiazolidine-4-carbonyl)amino]methyl]cyclohexyl]methyl nitrate Chemical compound O([N+](=O)[O-])CC1CCC(CC1)CNC(=O)C1NC(SC1C)=O XESZSJIJMJQGSY-UHFFFAOYSA-N 0.000 claims description 2
- WLGTXMASZMVRTN-UHFFFAOYSA-N [O-][N+](=O)OCC1CCC(CCNC(=O)C2CSC(=O)N2)CC1 Chemical compound [O-][N+](=O)OCC1CCC(CCNC(=O)C2CSC(=O)N2)CC1 WLGTXMASZMVRTN-UHFFFAOYSA-N 0.000 claims description 2
- RYCHWWVPNOYVRY-UHFFFAOYSA-N [O-][N+](=O)OCCCCC1CCC(CNC(=O)C2CSC(=O)N2)CC1 Chemical compound [O-][N+](=O)OCCCCC1CCC(CNC(=O)C2CSC(=O)N2)CC1 RYCHWWVPNOYVRY-UHFFFAOYSA-N 0.000 claims description 2
- 238000011321 prophylaxis Methods 0.000 claims 2
- 238000011282 treatment Methods 0.000 claims 2
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- 229910052757 nitrogen Inorganic materials 0.000 abstract description 4
- 125000004433 nitrogen atom Chemical group N* 0.000 abstract description 4
- 125000001424 substituent group Chemical group 0.000 abstract description 3
- 125000004430 oxygen atom Chemical group O* 0.000 abstract 2
- 125000000547 substituted alkyl group Chemical group 0.000 abstract 2
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 abstract 1
- 229910004679 ONO2 Inorganic materials 0.000 abstract 1
- 125000006615 aromatic heterocyclic group Chemical group 0.000 abstract 1
- 125000003118 aryl group Chemical group 0.000 abstract 1
- 125000005346 substituted cycloalkyl group Chemical group 0.000 abstract 1
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- 239000000243 solution Substances 0.000 description 160
- 238000000034 method Methods 0.000 description 136
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 126
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 114
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- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 102
- 239000007787 solid Substances 0.000 description 101
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- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 54
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- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 51
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- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 49
- 238000006243 chemical reaction Methods 0.000 description 49
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 48
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 45
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 45
- 238000001816 cooling Methods 0.000 description 44
- 238000003756 stirring Methods 0.000 description 42
- 238000010898 silica gel chromatography Methods 0.000 description 38
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 37
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 33
- 239000002253 acid Substances 0.000 description 33
- 239000012442 inert solvent Substances 0.000 description 33
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 31
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 27
- 238000001914 filtration Methods 0.000 description 26
- 125000006239 protecting group Chemical group 0.000 description 25
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 24
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 24
- 235000017557 sodium bicarbonate Nutrition 0.000 description 24
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 23
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 22
- 239000003921 oil Substances 0.000 description 21
- 239000012230 colorless oil Substances 0.000 description 20
- 239000003480 eluent Substances 0.000 description 20
- BMLMGCPTLHPWPY-REOHCLBHSA-N (4R)-2-oxo-4-thiazolidinecarboxylic acid Chemical compound OC(=O)[C@@H]1CSC(=O)N1 BMLMGCPTLHPWPY-REOHCLBHSA-N 0.000 description 18
- WORJRXHJTUTINR-UHFFFAOYSA-N 1,4-dioxane;hydron;chloride Chemical compound Cl.C1COCCO1 WORJRXHJTUTINR-UHFFFAOYSA-N 0.000 description 18
- NOTFZGFABLVTIG-UHFFFAOYSA-N Cyclohexylethyl acetate Chemical compound CC(=O)OCCC1CCCCC1 NOTFZGFABLVTIG-UHFFFAOYSA-N 0.000 description 18
- 150000002170 ethers Chemical class 0.000 description 18
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 18
- DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 18
- 230000000694 effects Effects 0.000 description 17
- 238000010992 reflux Methods 0.000 description 17
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 16
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 16
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- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 15
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 15
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
- 235000015165 citric acid Nutrition 0.000 description 15
- 150000004820 halides Chemical class 0.000 description 15
- 239000002585 base Substances 0.000 description 14
- GKIRPKYJQBWNGO-OCEACIFDSA-N clomifene Chemical compound C1=CC(OCCN(CC)CC)=CC=C1C(\C=1C=CC=CC=1)=C(\Cl)C1=CC=CC=C1 GKIRPKYJQBWNGO-OCEACIFDSA-N 0.000 description 14
- UKVIEHSSVKSQBA-UHFFFAOYSA-N methane;palladium Chemical compound C.[Pd] UKVIEHSSVKSQBA-UHFFFAOYSA-N 0.000 description 13
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 12
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 12
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 12
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
- 125000003277 amino group Chemical group 0.000 description 12
- 239000000284 extract Substances 0.000 description 12
- 239000000706 filtrate Substances 0.000 description 12
- 238000002844 melting Methods 0.000 description 12
- 230000008018 melting Effects 0.000 description 12
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 11
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 11
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- 150000001408 amides Chemical class 0.000 description 11
- 150000008282 halocarbons Chemical class 0.000 description 11
- 229910052739 hydrogen Inorganic materials 0.000 description 11
- 239000001257 hydrogen Substances 0.000 description 11
- 239000007858 starting material Substances 0.000 description 11
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 10
- 150000008065 acid anhydrides Chemical class 0.000 description 10
- 150000001412 amines Chemical class 0.000 description 10
- RBHJBMIOOPYDBQ-UHFFFAOYSA-N carbon dioxide;propan-2-one Chemical compound O=C=O.CC(C)=O RBHJBMIOOPYDBQ-UHFFFAOYSA-N 0.000 description 10
- 150000002148 esters Chemical class 0.000 description 10
- 238000004809 thin layer chromatography Methods 0.000 description 10
- 239000012280 lithium aluminium hydride Substances 0.000 description 9
- 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 8
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 8
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- FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 8
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 7
- 229910052783 alkali metal Inorganic materials 0.000 description 7
- 230000003197 catalytic effect Effects 0.000 description 7
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- 229940124597 therapeutic agent Drugs 0.000 description 7
- YOETUEMZNOLGDB-UHFFFAOYSA-N 2-methylpropyl carbonochloridate Chemical compound CC(C)COC(Cl)=O YOETUEMZNOLGDB-UHFFFAOYSA-N 0.000 description 6
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- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 6
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- 235000019270 ammonium chloride Nutrition 0.000 description 6
- 239000007864 aqueous solution Substances 0.000 description 6
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 6
- 125000004432 carbon atom Chemical group C* 0.000 description 6
- 239000013078 crystal Substances 0.000 description 6
- 229910052736 halogen Inorganic materials 0.000 description 6
- 150000002367 halogens Chemical class 0.000 description 6
- 125000001841 imino group Chemical group [H]N=* 0.000 description 6
- IZDROVVXIHRYMH-UHFFFAOYSA-N methanesulfonic anhydride Chemical compound CS(=O)(=O)OS(C)(=O)=O IZDROVVXIHRYMH-UHFFFAOYSA-N 0.000 description 6
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 6
- 239000012279 sodium borohydride Substances 0.000 description 6
- 229910000033 sodium borohydride Inorganic materials 0.000 description 6
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- 150000003462 sulfoxides Chemical class 0.000 description 6
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- 125000004209 (C1-C8) alkyl group Chemical group 0.000 description 5
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- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 4
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- AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 4
- 235000019345 sodium thiosulphate Nutrition 0.000 description 4
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 4
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- 235000011152 sodium sulphate 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
- 239000000600 sorbitol Substances 0.000 description 1
- 235000019385 spermaceti wax Nutrition 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 238000009495 sugar coating Methods 0.000 description 1
- BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- GFYHSKONPJXCDE-UHFFFAOYSA-N sym-collidine Natural products CC1=CN=C(C)C(C)=C1 GFYHSKONPJXCDE-UHFFFAOYSA-N 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- BVRGLGJXQIMHBS-UHFFFAOYSA-N tert-butyl carbonobromidate Chemical compound CC(C)(C)OC(Br)=O BVRGLGJXQIMHBS-UHFFFAOYSA-N 0.000 description 1
- UJJDEOLXODWCGK-UHFFFAOYSA-N tert-butyl carbonochloridate Chemical compound CC(C)(C)OC(Cl)=O UJJDEOLXODWCGK-UHFFFAOYSA-N 0.000 description 1
- NBRKLOOSMBRFMH-UHFFFAOYSA-N tert-butyl chloride Chemical compound CC(C)(C)Cl NBRKLOOSMBRFMH-UHFFFAOYSA-N 0.000 description 1
- LBJSEPNOVVUVJA-UHFFFAOYSA-N tert-butyl n-[3-(hydroxymethyl)cyclohexyl]carbamate Chemical compound CC(C)(C)OC(=O)NC1CCCC(CO)C1 LBJSEPNOVVUVJA-UHFFFAOYSA-N 0.000 description 1
- SGNKPJPMWHKOJO-UHFFFAOYSA-N tert-butyl n-[4-(hydroxymethyl)cyclohexyl]carbamate Chemical compound CC(C)(C)OC(=O)NC1CCC(CO)CC1 SGNKPJPMWHKOJO-UHFFFAOYSA-N 0.000 description 1
- VCIBBCGSWUMTGW-QWRGUYRKSA-N tert-butyl n-[[(1r,2r)-2-(hydroxymethyl)cyclohexyl]methyl]carbamate Chemical compound CC(C)(C)OC(=O)NC[C@@H]1CCCC[C@H]1CO VCIBBCGSWUMTGW-QWRGUYRKSA-N 0.000 description 1
- RTKIYNMVFMVABJ-UHFFFAOYSA-L thimerosal Chemical compound [Na+].CC[Hg]SC1=CC=CC=C1C([O-])=O RTKIYNMVFMVABJ-UHFFFAOYSA-L 0.000 description 1
- 229940033663 thimerosal Drugs 0.000 description 1
- 210000001685 thyroid gland Anatomy 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- ILWRPSCZWQJDMK-UHFFFAOYSA-N triethylazanium;chloride Chemical compound Cl.CCN(CC)CC ILWRPSCZWQJDMK-UHFFFAOYSA-N 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
- 238000011144 upstream manufacturing Methods 0.000 description 1
- 125000003774 valeryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
- 239000001993 wax Substances 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D263/00—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings
- C07D263/02—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings
- C07D263/08—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
- C07D263/16—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D263/18—Oxygen atoms
- C07D263/20—Oxygen atoms attached in position 2
-
- 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
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
- C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
- C07D277/08—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
- C07D277/12—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D277/14—Oxygen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
- C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
- C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D277/22—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
- C07D277/30—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Urology & Nephrology (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Vascular Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Thiazole And Isothizaole Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP31151194 | 1994-12-15 | ||
PCT/JP1995/002545 WO1996018620A1 (fr) | 1994-12-15 | 1995-12-13 | Composes thiazolidinone ou medicament pour prevenir ou guerir l'angine de poitrine contenant ces composes en tant qu'ingredient actif |
Publications (3)
Publication Number | Publication Date |
---|---|
NO972731D0 NO972731D0 (no) | 1997-06-13 |
NO972731L NO972731L (no) | 1997-08-14 |
NO309475B1 true NO309475B1 (no) | 2001-02-05 |
Family
ID=18018119
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
NO972731A NO309475B1 (no) | 1994-12-15 | 1997-06-13 | Tiazolidinonforbindelser og terapeutisk eller forhindrende middel mot angina pectoris omfattende forbindelsene som aktiv bestanddel |
Country Status (21)
Country | Link |
---|---|
US (1) | US5843973A (da) |
EP (1) | EP0798298B1 (da) |
KR (1) | KR100312471B1 (da) |
CN (1) | CN1092649C (da) |
AT (1) | ATE203987T1 (da) |
AU (1) | AU692334B2 (da) |
CA (1) | CA2207794A1 (da) |
CZ (1) | CZ292626B6 (da) |
DE (1) | DE69522118T2 (da) |
DK (1) | DK0798298T3 (da) |
ES (1) | ES2161916T3 (da) |
FI (1) | FI972510A (da) |
GR (1) | GR3036704T3 (da) |
HK (1) | HK1000494A1 (da) |
HU (1) | HUT77131A (da) |
MX (1) | MX9704435A (da) |
NO (1) | NO309475B1 (da) |
NZ (1) | NZ297095A (da) |
PT (1) | PT798298E (da) |
RU (1) | RU2139283C1 (da) |
WO (1) | WO1996018620A1 (da) |
Families Citing this family (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
TW200524849A (en) * | 2003-07-02 | 2005-08-01 | Hoffmann La Roche | Hydroxyalkylamide derivatives |
EP1692121A1 (en) | 2003-11-18 | 2006-08-23 | University of Tennessee Research Foundation | Thiazolidinone amides, thiazolidine carboxylic acid amides, methods of making, and uses thereof |
TR201903981T4 (tr) | 2008-06-16 | 2019-04-22 | Univ Ohio State Res Found | Kanser tedavisi için bileşikler. |
US9447049B2 (en) | 2010-03-01 | 2016-09-20 | University Of Tennessee Research Foundation | Compounds for treatment of cancer |
US8822513B2 (en) | 2010-03-01 | 2014-09-02 | Gtx, Inc. | Compounds for treatment of cancer |
US9029408B2 (en) | 2008-06-16 | 2015-05-12 | Gtx, Inc. | Compounds for treatment of cancer |
EP2290114A1 (de) | 2009-08-04 | 2011-03-02 | Gebr. Kemper GmbH + Co. KG Metallwerke | Wasserführendes Bauteil |
JP5879273B2 (ja) | 2010-03-01 | 2016-03-08 | ジーティーエックス・インコーポレイテッド | 癌を処置するための化合物 |
Family Cites Families (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPS5213910A (en) * | 1975-07-19 | 1977-02-02 | Toshinori Kawabuchi | Photogravure printing press |
GB8717068D0 (en) * | 1987-07-20 | 1987-08-26 | Fujisawa Pharmaceutical Co | Nitric ester derivative |
AU647599B2 (en) * | 1991-03-27 | 1994-03-24 | Sankyo Company Limited | New thiazolidinone and oxazolidinone derivatives, their preparation and their use as vasodilators |
CZ290989B6 (cs) * | 1995-03-02 | 2002-11-13 | Sankyo Company, Limited | Opticky aktivní thiazolidinonový derivát, prostředek jej obsahující, pouľití tohoto derivátu a způsob jeho přípravy |
-
1995
- 1995-12-13 DE DE69522118T patent/DE69522118T2/de not_active Expired - Fee Related
- 1995-12-13 WO PCT/JP1995/002545 patent/WO1996018620A1/ja active IP Right Grant
- 1995-12-13 EP EP95940418A patent/EP0798298B1/en not_active Expired - Lifetime
- 1995-12-13 NZ NZ297095A patent/NZ297095A/en unknown
- 1995-12-13 AU AU41879/96A patent/AU692334B2/en not_active Ceased
- 1995-12-13 RU RU97111807A patent/RU2139283C1/ru not_active IP Right Cessation
- 1995-12-13 AT AT95940418T patent/ATE203987T1/de not_active IP Right Cessation
- 1995-12-13 MX MX9704435A patent/MX9704435A/es unknown
- 1995-12-13 CN CN95197632A patent/CN1092649C/zh not_active Expired - Fee Related
- 1995-12-13 CA CA002207794A patent/CA2207794A1/en not_active Abandoned
- 1995-12-13 KR KR1019970704021A patent/KR100312471B1/ko not_active IP Right Cessation
- 1995-12-13 DK DK95940418T patent/DK0798298T3/da active
- 1995-12-13 ES ES95940418T patent/ES2161916T3/es not_active Expired - Lifetime
- 1995-12-13 HU HU9701951A patent/HUT77131A/hu unknown
- 1995-12-13 CZ CZ19971834A patent/CZ292626B6/cs not_active IP Right Cessation
- 1995-12-13 PT PT95940418T patent/PT798298E/pt unknown
-
1997
- 1997-06-10 US US08/872,770 patent/US5843973A/en not_active Expired - Fee Related
- 1997-06-13 FI FI972510A patent/FI972510A/fi not_active IP Right Cessation
- 1997-06-13 NO NO972731A patent/NO309475B1/no unknown
- 1997-10-17 HK HK97101943A patent/HK1000494A1/xx not_active IP Right Cessation
-
2001
- 2001-09-26 GR GR20010401561T patent/GR3036704T3/el not_active IP Right Cessation
Also Published As
Publication number | Publication date |
---|---|
CN1092649C (zh) | 2002-10-16 |
NO972731L (no) | 1997-08-14 |
DK0798298T3 (da) | 2001-10-22 |
GR3036704T3 (en) | 2001-12-31 |
RU2139283C1 (ru) | 1999-10-10 |
FI972510A (fi) | 1997-08-07 |
EP0798298B1 (en) | 2001-08-08 |
ATE203987T1 (de) | 2001-08-15 |
EP0798298A1 (en) | 1997-10-01 |
US5843973A (en) | 1998-12-01 |
DE69522118D1 (de) | 2001-09-13 |
KR100312471B1 (ko) | 2002-02-28 |
FI972510A0 (fi) | 1997-06-13 |
CZ183497A3 (en) | 1997-12-17 |
CN1175250A (zh) | 1998-03-04 |
DE69522118T2 (de) | 2002-04-25 |
AU692334B2 (en) | 1998-06-04 |
AU4187996A (en) | 1996-07-03 |
PT798298E (pt) | 2001-11-30 |
HK1000494A1 (en) | 2002-03-15 |
EP0798298A4 (en) | 1998-03-25 |
WO1996018620A1 (fr) | 1996-06-20 |
CA2207794A1 (en) | 1996-06-20 |
HUT77131A (hu) | 1998-03-02 |
NO972731D0 (no) | 1997-06-13 |
CZ292626B6 (cs) | 2003-11-12 |
NZ297095A (en) | 1998-09-24 |
ES2161916T3 (es) | 2001-12-16 |
MX9704435A (es) | 1997-10-31 |
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