NO306066B1 - Ny 7-substituert oksasteroidforbindelse - Google Patents
Ny 7-substituert oksasteroidforbindelse Download PDFInfo
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- NO306066B1 NO306066B1 NO951211A NO951211A NO306066B1 NO 306066 B1 NO306066 B1 NO 306066B1 NO 951211 A NO951211 A NO 951211A NO 951211 A NO951211 A NO 951211A NO 306066 B1 NO306066 B1 NO 306066B1
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- NO
- Norway
- Prior art keywords
- group
- homo
- oxaandrosta
- compound
- dione
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- -1 oxasteroid compound Chemical class 0.000 title claims abstract description 30
- 150000001875 compounds Chemical class 0.000 claims abstract description 80
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 25
- 125000002252 acyl group Chemical group 0.000 claims abstract description 10
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 10
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims abstract description 9
- 239000000262 estrogen Substances 0.000 claims abstract description 9
- 125000001424 substituent group Chemical group 0.000 claims abstract description 9
- 150000003431 steroids Chemical class 0.000 claims abstract description 8
- 125000003342 alkenyl group Chemical group 0.000 claims abstract description 7
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 7
- 201000010099 disease Diseases 0.000 claims abstract description 6
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 6
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims abstract description 5
- 239000000203 mixture Substances 0.000 claims description 56
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 18
- 125000003277 amino group Chemical group 0.000 claims description 5
- 239000003886 aromatase inhibitor Substances 0.000 claims description 4
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 4
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 3
- 238000002360 preparation method Methods 0.000 claims description 3
- 125000005115 alkyl carbamoyl group Chemical group 0.000 claims description 2
- 229940122815 Aromatase inhibitor Drugs 0.000 claims 1
- 239000008194 pharmaceutical composition Substances 0.000 claims 1
- 102000014654 Aromatase Human genes 0.000 abstract description 15
- 108010078554 Aromatase Proteins 0.000 abstract description 15
- 230000002401 inhibitory effect Effects 0.000 abstract description 12
- 229940011871 estrogen Drugs 0.000 abstract description 7
- 206010006187 Breast cancer Diseases 0.000 abstract description 4
- 208000026310 Breast neoplasm Diseases 0.000 abstract description 4
- 208000002495 Uterine Neoplasms Diseases 0.000 abstract description 4
- 206010046766 uterine cancer Diseases 0.000 abstract description 4
- 206010020880 Hypertrophy Diseases 0.000 abstract description 2
- 125000005842 heteroatom Chemical group 0.000 abstract description 2
- 230000002265 prevention Effects 0.000 abstract description 2
- 210000002307 prostate Anatomy 0.000 abstract description 2
- 125000003710 aryl alkyl group Chemical group 0.000 abstract 2
- 125000003545 alkoxy group Chemical group 0.000 abstract 1
- 125000003118 aryl group Chemical group 0.000 abstract 1
- 125000005843 halogen group Chemical group 0.000 abstract 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 150
- 239000000243 solution Substances 0.000 description 88
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 59
- 238000005160 1H NMR spectroscopy Methods 0.000 description 57
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 54
- 238000004809 thin layer chromatography Methods 0.000 description 46
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 45
- 239000000047 product Substances 0.000 description 44
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 42
- 239000012043 crude product Substances 0.000 description 40
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 38
- 239000002904 solvent Substances 0.000 description 38
- 238000006243 chemical reaction Methods 0.000 description 37
- 239000011541 reaction mixture Substances 0.000 description 35
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 33
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 28
- 238000000034 method Methods 0.000 description 27
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 24
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 24
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 23
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 23
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 21
- 235000017557 sodium bicarbonate Nutrition 0.000 description 19
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 19
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 18
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 18
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 16
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 14
- 125000000446 sulfanediyl group Chemical group *S* 0.000 description 14
- 239000012299 nitrogen atmosphere Substances 0.000 description 13
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 11
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 10
- 239000012442 inert solvent Substances 0.000 description 10
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 9
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
- UKJLNMAFNRKWGR-UHFFFAOYSA-N cyclohexatrienamine Chemical group NC1=CC=C=C[CH]1 UKJLNMAFNRKWGR-UHFFFAOYSA-N 0.000 description 9
- 238000004519 manufacturing process Methods 0.000 description 9
- 238000010992 reflux Methods 0.000 description 9
- RMVRSNDYEFQCLF-UHFFFAOYSA-N thiophenol Chemical compound SC1=CC=CC=C1 RMVRSNDYEFQCLF-UHFFFAOYSA-N 0.000 description 9
- HZNVUJQVZSTENZ-UHFFFAOYSA-N 2,3-dichloro-5,6-dicyano-1,4-benzoquinone Chemical compound ClC1=C(Cl)C(=O)C(C#N)=C(C#N)C1=O HZNVUJQVZSTENZ-UHFFFAOYSA-N 0.000 description 8
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 8
- 229960004132 diethyl ether Drugs 0.000 description 8
- 239000003513 alkali Substances 0.000 description 7
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 7
- 230000007306 turnover Effects 0.000 description 7
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- 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 6
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 6
- PASDCCFISLVPSO-UHFFFAOYSA-N benzoyl chloride Chemical compound ClC(=O)C1=CC=CC=C1 PASDCCFISLVPSO-UHFFFAOYSA-N 0.000 description 6
- 230000006003 cornification Effects 0.000 description 6
- DNJIEGIFACGWOD-UHFFFAOYSA-N ethanethiol Chemical compound CCS DNJIEGIFACGWOD-UHFFFAOYSA-N 0.000 description 6
- 125000004043 oxo group Chemical group O=* 0.000 description 6
- 239000011734 sodium Substances 0.000 description 6
- 229910052708 sodium Inorganic materials 0.000 description 6
- 125000003396 thiol group Chemical group [H]S* 0.000 description 6
- 241000282414 Homo sapiens Species 0.000 description 5
- CZWCKYRVOZZJNM-UHFFFAOYSA-N Prasterone sodium sulfate Natural products C1C(OS(O)(=O)=O)CCC2(C)C3CCC(C)(C(CC4)=O)C4C3CC=C21 CZWCKYRVOZZJNM-UHFFFAOYSA-N 0.000 description 5
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 5
- CZWCKYRVOZZJNM-USOAJAOKSA-N dehydroepiandrosterone sulfate Chemical compound C1[C@@H](OS(O)(=O)=O)CC[C@]2(C)[C@H]3CC[C@](C)(C(CC4)=O)[C@@H]4[C@@H]3CC=C21 CZWCKYRVOZZJNM-USOAJAOKSA-N 0.000 description 5
- 229950009829 prasterone sulfate Drugs 0.000 description 5
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 5
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 4
- WTEOIRVLGSZEPR-UHFFFAOYSA-N boron trifluoride Chemical compound FB(F)F WTEOIRVLGSZEPR-UHFFFAOYSA-N 0.000 description 4
- ORTQZVOHEJQUHG-UHFFFAOYSA-L copper(II) chloride Chemical compound Cl[Cu]Cl ORTQZVOHEJQUHG-UHFFFAOYSA-L 0.000 description 4
- 239000008187 granular material Substances 0.000 description 4
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
- 238000007254 oxidation reaction Methods 0.000 description 4
- 239000008177 pharmaceutical agent Substances 0.000 description 4
- WYVAMUWZEOHJOQ-UHFFFAOYSA-N propionic anhydride Chemical compound CCC(=O)OC(=O)CC WYVAMUWZEOHJOQ-UHFFFAOYSA-N 0.000 description 4
- 239000007787 solid Substances 0.000 description 4
- 239000007858 starting material Substances 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- 238000012360 testing method Methods 0.000 description 4
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 4
- AQRLNPVMDITEJU-UHFFFAOYSA-N triethylsilane Chemical compound CC[SiH](CC)CC AQRLNPVMDITEJU-UHFFFAOYSA-N 0.000 description 4
- ULIKDJVNUXNQHS-UHFFFAOYSA-N 2-Propene-1-thiol Chemical compound SCC=C ULIKDJVNUXNQHS-UHFFFAOYSA-N 0.000 description 3
- LDLCZOVUSADOIV-UHFFFAOYSA-N 2-bromoethanol Chemical compound OCCBr LDLCZOVUSADOIV-UHFFFAOYSA-N 0.000 description 3
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 description 3
- NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 3
- WCDSVWRUXWCYFN-UHFFFAOYSA-N 4-aminobenzenethiol Chemical compound NC1=CC=C(S)C=C1 WCDSVWRUXWCYFN-UHFFFAOYSA-N 0.000 description 3
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 229920002472 Starch Polymers 0.000 description 3
- 229910052783 alkali metal Inorganic materials 0.000 description 3
- 238000005804 alkylation reaction Methods 0.000 description 3
- AEMFNILZOJDQLW-QAGGRKNESA-N androst-4-ene-3,17-dione Chemical class O=C1CC[C@]2(C)[C@H]3CC[C@](C)(C(CC4)=O)[C@@H]4[C@@H]3CCC2=C1 AEMFNILZOJDQLW-QAGGRKNESA-N 0.000 description 3
- 229940046844 aromatase inhibitors Drugs 0.000 description 3
- 239000003153 chemical reaction reagent Substances 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 230000007062 hydrolysis Effects 0.000 description 3
- 238000006460 hydrolysis reaction Methods 0.000 description 3
- 238000011534 incubation Methods 0.000 description 3
- 210000001589 microsome Anatomy 0.000 description 3
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- 125000006239 protecting group Chemical group 0.000 description 3
- KOUKXHPPRFNWPP-UHFFFAOYSA-N pyrazine-2,5-dicarboxylic acid;hydrate Chemical compound O.OC(=O)C1=CN=C(C(O)=O)C=N1 KOUKXHPPRFNWPP-UHFFFAOYSA-N 0.000 description 3
- 239000012312 sodium hydride Substances 0.000 description 3
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- 239000008107 starch Substances 0.000 description 3
- 235000019698 starch Nutrition 0.000 description 3
- AZQWKYJCGOJGHM-UHFFFAOYSA-N 1,4-benzoquinone Chemical compound O=C1C=CC(=O)C=C1 AZQWKYJCGOJGHM-UHFFFAOYSA-N 0.000 description 2
- 229910015900 BF3 Inorganic materials 0.000 description 2
- 206010004446 Benign prostatic hyperplasia Diseases 0.000 description 2
- YIIMEMSDCNDGTB-UHFFFAOYSA-N Dimethylcarbamoyl chloride Chemical compound CN(C)C(Cl)=O YIIMEMSDCNDGTB-UHFFFAOYSA-N 0.000 description 2
- 201000009273 Endometriosis Diseases 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
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- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 2
- 241000124008 Mammalia Species 0.000 description 2
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- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 2
- GOQKZPYEPNPUKZ-UHFFFAOYSA-M [Cl-].C1CCOC1.[Mg+]CC1=CC=CC=C1 Chemical compound [Cl-].C1CCOC1.[Mg+]CC1=CC=CC=C1 GOQKZPYEPNPUKZ-UHFFFAOYSA-M 0.000 description 2
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 2
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- 150000001340 alkali metals Chemical class 0.000 description 2
- 125000004414 alkyl thio group Chemical group 0.000 description 2
- 230000029936 alkylation Effects 0.000 description 2
- 229960005471 androstenedione Drugs 0.000 description 2
- AEMFNILZOJDQLW-UHFFFAOYSA-N androstenedione Natural products O=C1CCC2(C)C3CCC(C)(C(CC4)=O)C4C3CCC2=C1 AEMFNILZOJDQLW-UHFFFAOYSA-N 0.000 description 2
- 238000003556 assay Methods 0.000 description 2
- 206010003883 azoospermia Diseases 0.000 description 2
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- RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 description 2
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- OSVMTWJCGUFAOD-KZQROQTASA-N formestane Chemical compound O=C1CC[C@]2(C)[C@H]3CC[C@](C)(C(CC4)=O)[C@@H]4[C@@H]3CCC2=C1O OSVMTWJCGUFAOD-KZQROQTASA-N 0.000 description 2
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- GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 2
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- WWVGOVDLTMQAQT-RCMKLKEOSA-N (3as,3br,9ar,9bs,11as)-9a,11a-dimethyl-3,3a,3b,4,5,9b,10,11-octahydronaphtho[2,1-e][2]benzofuran-1,7-dione Chemical compound O=C1C=C[C@]2(C)[C@H]3CC[C@](C)(C(OC4)=O)[C@@H]4[C@@H]3CCC2=C1 WWVGOVDLTMQAQT-RCMKLKEOSA-N 0.000 description 1
- OWEGMIWEEQEYGQ-UHFFFAOYSA-N 100676-05-9 Natural products OC1C(O)C(O)C(CO)OC1OCC1C(O)C(O)C(O)C(OC2C(OC(O)C(O)C2O)CO)O1 OWEGMIWEEQEYGQ-UHFFFAOYSA-N 0.000 description 1
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- ZLNQQNXFFQJAID-UHFFFAOYSA-L magnesium carbonate Chemical compound [Mg+2].[O-]C([O-])=O ZLNQQNXFFQJAID-UHFFFAOYSA-L 0.000 description 1
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- 150000007524 organic acids Chemical class 0.000 description 1
- 239000012044 organic layer Substances 0.000 description 1
- 150000002914 oxasteroids Chemical class 0.000 description 1
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 125000003356 phenylsulfanyl group Chemical group [*]SC1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
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- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 1
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- 229920000053 polysorbate 80 Polymers 0.000 description 1
- 229940068968 polysorbate 80 Drugs 0.000 description 1
- 229910000105 potassium hydride Inorganic materials 0.000 description 1
- NTTOTNSKUYCDAV-UHFFFAOYSA-N potassium hydride Chemical compound [KH] NTTOTNSKUYCDAV-UHFFFAOYSA-N 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
- WGYKZJWCGVVSQN-UHFFFAOYSA-N propylamine Chemical group CCCN WGYKZJWCGVVSQN-UHFFFAOYSA-N 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 238000007790 scraping Methods 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 238000010898 silica gel chromatography Methods 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 1
- 239000001488 sodium phosphate Substances 0.000 description 1
- 229910000162 sodium phosphate Inorganic materials 0.000 description 1
- 235000010265 sodium sulphite Nutrition 0.000 description 1
- SUBJHSREKVAVAR-UHFFFAOYSA-N sodium;methanol;methanolate Chemical compound [Na+].OC.[O-]C SUBJHSREKVAVAR-UHFFFAOYSA-N 0.000 description 1
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- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- BPEWUONYVDABNZ-DZBHQSCQSA-N testolactone Chemical compound O=C1C=C[C@]2(C)[C@H]3CC[C@](C)(OC(=O)CC4)[C@@H]4[C@@H]3CCC2=C1 BPEWUONYVDABNZ-DZBHQSCQSA-N 0.000 description 1
- 229960005353 testolactone Drugs 0.000 description 1
- UGNWTBMOAKPKBL-UHFFFAOYSA-N tetrachloro-1,4-benzoquinone Chemical compound ClC1=C(Cl)C(=O)C(Cl)=C(Cl)C1=O UGNWTBMOAKPKBL-UHFFFAOYSA-N 0.000 description 1
- 125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
- 229940099259 vaseline Drugs 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J31/00—Normal steroids containing one or more sulfur atoms not belonging to a hetero ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J73/00—Steroids in which the cyclopenta[a]hydrophenanthrene skeleton has been modified by substitution of one or two carbon atoms by hetero atoms
- C07J73/001—Steroids in which the cyclopenta[a]hydrophenanthrene skeleton has been modified by substitution of one or two carbon atoms by hetero atoms by one hetero atom
- C07J73/005—Steroids in which the cyclopenta[a]hydrophenanthrene skeleton has been modified by substitution of one or two carbon atoms by hetero atoms by one hetero atom by nitrogen as hetero atom
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/08—Drugs for disorders of the urinary system of the prostate
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J73/00—Steroids in which the cyclopenta[a]hydrophenanthrene skeleton has been modified by substitution of one or two carbon atoms by hetero atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J73/00—Steroids in which the cyclopenta[a]hydrophenanthrene skeleton has been modified by substitution of one or two carbon atoms by hetero atoms
- C07J73/001—Steroids in which the cyclopenta[a]hydrophenanthrene skeleton has been modified by substitution of one or two carbon atoms by hetero atoms by one hetero atom
- C07J73/003—Steroids in which the cyclopenta[a]hydrophenanthrene skeleton has been modified by substitution of one or two carbon atoms by hetero atoms by one hetero atom by oxygen as hetero atom
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- General Chemical & Material Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Veterinary Medicine (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Urology & Nephrology (AREA)
- Steroid Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP28361692 | 1992-09-30 | ||
| PCT/JP1993/001390 WO1994007908A1 (en) | 1992-09-30 | 1993-09-29 | Novel 7-substituted oxa- or azasteroid compound |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| NO951211D0 NO951211D0 (no) | 1995-03-29 |
| NO951211L NO951211L (no) | 1995-05-30 |
| NO306066B1 true NO306066B1 (no) | 1999-09-13 |
Family
ID=17667815
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO951211A NO306066B1 (no) | 1992-09-30 | 1995-03-29 | Ny 7-substituert oksasteroidforbindelse |
Country Status (18)
| Country | Link |
|---|---|
| US (1) | US5539127A (da) |
| EP (1) | EP0663402B1 (da) |
| JP (1) | JP3293629B2 (da) |
| KR (1) | KR100231638B1 (da) |
| AT (1) | ATE179179T1 (da) |
| AU (1) | AU665455B2 (da) |
| CA (1) | CA2145643A1 (da) |
| DE (1) | DE69324595T2 (da) |
| DK (1) | DK0663402T3 (da) |
| ES (1) | ES2130284T3 (da) |
| FI (1) | FI114799B (da) |
| GR (1) | GR3030245T3 (da) |
| HU (1) | HU221191B1 (da) |
| NO (1) | NO306066B1 (da) |
| NZ (1) | NZ256130A (da) |
| PL (1) | PL176114B1 (da) |
| SG (1) | SG48172A1 (da) |
| WO (1) | WO1994007908A1 (da) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5245275A (en) * | 1989-09-25 | 1993-09-14 | General Electric Company | Electronic watthour meter |
| DE19610645A1 (de) * | 1996-03-06 | 1997-09-11 | Schering Ag | Kombination von Dehydroepiandrosteron und Aromatasehemmern und Verwendung dieser Kombination zur Herstellung eines Arzeimittels zur Behandlung eines relativen und absoluten Androgenmangels beim Mann |
| WO2008104583A1 (de) * | 2007-03-01 | 2008-09-04 | Basf Se | Verfahren zur herstellung von ethylenaminen |
Family Cites Families (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4116978A (en) * | 1977-07-20 | 1978-09-26 | E. R. Squibb & Sons, Inc. | D-homo oxasteroids |
| US4235893A (en) * | 1978-05-08 | 1980-11-25 | Brodie Angela M | Ester derivatives of 4-hydroxy-4-androstene-3,17-dione and a method for inhibiting estrogen biosynthesis |
| DE3322285A1 (de) * | 1983-06-18 | 1984-12-20 | Schering AG, 1000 Berlin und 4709 Bergkamen | 1-alkyl-androsta-1,4-dien-3,17-dione, verfahren zu deren herstellung und diese enthaltende pharmazeutische praeparate |
| GB8503940D0 (en) * | 1985-02-15 | 1985-03-20 | Erba Farmitalia | 4-substituted androstendione derivatives |
| DE3622841C2 (de) * | 1985-07-09 | 2001-01-25 | Pharmacia & Upjohn Spa | Substituierte Androsta-1,4-dien-3,17-dione und Verfahren zu deren Herstellung |
| GB8517360D0 (en) * | 1985-07-09 | 1985-08-14 | Erba Farmitalia | Substituted androsta-1,4-diene-3,17-diones |
| US5227375A (en) * | 1990-02-08 | 1993-07-13 | Endorecherche, Inc. | Aromatase inhibitors |
| US5219879A (en) * | 1990-03-05 | 1993-06-15 | Du Pont Merck Pharmaceutical Company | Heterocyclic steroid compounds |
| ATE154032T1 (de) * | 1991-03-28 | 1997-06-15 | Teikoku Hormone Mfg Co Ltd | Neue d-homo-17-oxa und d-homo-17-aza- androstanderivate |
| JPH05148294A (ja) * | 1991-11-27 | 1993-06-15 | Teikoku Hormone Mfg Co Ltd | ３，５−ジエンステロイド誘導体 |
-
1993
- 1993-09-29 DE DE69324595T patent/DE69324595T2/de not_active Expired - Fee Related
- 1993-09-29 WO PCT/JP1993/001390 patent/WO1994007908A1/ja active IP Right Grant
- 1993-09-29 DK DK93921086T patent/DK0663402T3/da active
- 1993-09-29 NZ NZ256130A patent/NZ256130A/en unknown
- 1993-09-29 JP JP50889794A patent/JP3293629B2/ja not_active Expired - Fee Related
- 1993-09-29 SG SG1996007586A patent/SG48172A1/en unknown
- 1993-09-29 ES ES93921086T patent/ES2130284T3/es not_active Expired - Lifetime
- 1993-09-29 AT AT93921086T patent/ATE179179T1/de not_active IP Right Cessation
- 1993-09-29 PL PL93308228A patent/PL176114B1/pl not_active IP Right Cessation
- 1993-09-29 CA CA002145643A patent/CA2145643A1/en not_active Abandoned
- 1993-09-29 EP EP93921086A patent/EP0663402B1/en not_active Expired - Lifetime
- 1993-09-29 US US08/403,867 patent/US5539127A/en not_active Expired - Fee Related
- 1993-09-29 AU AU48342/93A patent/AU665455B2/en not_active Ceased
- 1993-09-29 HU HU9500929A patent/HU221191B1/hu not_active IP Right Cessation
- 1993-09-29 KR KR1019950701233A patent/KR100231638B1/ko not_active IP Right Cessation
-
1995
- 1995-03-29 NO NO951211A patent/NO306066B1/no unknown
- 1995-03-29 FI FI951505A patent/FI114799B/fi active
-
1999
- 1999-05-19 GR GR990401338T patent/GR3030245T3/el unknown
Also Published As
| Publication number | Publication date |
|---|---|
| WO1994007908A1 (en) | 1994-04-14 |
| FI114799B (fi) | 2004-12-31 |
| KR100231638B1 (ko) | 1999-12-01 |
| JP3293629B2 (ja) | 2002-06-17 |
| DE69324595D1 (de) | 1999-05-27 |
| CA2145643A1 (en) | 1994-04-14 |
| GR3030245T3 (en) | 1999-08-31 |
| AU665455B2 (en) | 1996-01-04 |
| HU221191B1 (en) | 2002-08-28 |
| NO951211L (no) | 1995-05-30 |
| HU9500929D0 (en) | 1995-05-29 |
| EP0663402B1 (en) | 1999-04-21 |
| AU4834293A (en) | 1994-04-26 |
| DK0663402T3 (da) | 1999-10-25 |
| FI951505A (fi) | 1995-05-26 |
| DE69324595T2 (de) | 1999-08-19 |
| EP0663402A1 (en) | 1995-07-19 |
| EP0663402A4 (en) | 1996-06-12 |
| PL176114B1 (pl) | 1999-04-30 |
| ATE179179T1 (de) | 1999-05-15 |
| FI951505A0 (fi) | 1995-03-29 |
| HUT71519A (en) | 1995-12-28 |
| PL308228A1 (en) | 1995-07-24 |
| US5539127A (en) | 1996-07-23 |
| NZ256130A (en) | 1996-05-28 |
| NO951211D0 (no) | 1995-03-29 |
| ES2130284T3 (es) | 1999-07-01 |
| KR950703575A (ko) | 1995-09-20 |
| SG48172A1 (en) | 1998-04-17 |
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