DE2322532A1 - Pregnanderivate und verfahren zu ihrer herstellung - Google Patents
Pregnanderivate und verfahren zu ihrer herstellungInfo
- Publication number
- DE2322532A1 DE2322532A1 DE2322532A DE2322532A DE2322532A1 DE 2322532 A1 DE2322532 A1 DE 2322532A1 DE 2322532 A DE2322532 A DE 2322532A DE 2322532 A DE2322532 A DE 2322532A DE 2322532 A1 DE2322532 A1 DE 2322532A1
- Authority
- DE
- Germany
- Prior art keywords
- hydroxy
- dione
- pregnane
- steroid
- group
- 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.)
- Ceased
Links
- 238000000034 method Methods 0.000 title claims description 48
- 238000004519 manufacturing process Methods 0.000 title claims description 29
- 150000003431 steroids Chemical class 0.000 claims description 66
- 239000000203 mixture Substances 0.000 claims description 37
- -1 alkali metal cyanide Chemical class 0.000 claims description 24
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 23
- 229910052794 bromium Inorganic materials 0.000 claims description 22
- 230000003444 anaesthetic effect Effects 0.000 claims description 18
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 17
- 150000003839 salts Chemical class 0.000 claims description 17
- 229910052757 nitrogen Inorganic materials 0.000 claims description 15
- 125000001424 substituent group Chemical group 0.000 claims description 15
- 239000002253 acid Substances 0.000 claims description 13
- 238000006243 chemical reaction Methods 0.000 claims description 12
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 claims description 10
- 125000003277 amino group Chemical group 0.000 claims description 10
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 claims description 8
- 125000003545 alkoxy group Chemical group 0.000 claims description 8
- 229920006395 saturated elastomer Polymers 0.000 claims description 7
- 229910052783 alkali metal Inorganic materials 0.000 claims description 6
- 150000001412 amines Chemical class 0.000 claims description 6
- 235000010323 ascorbic acid Nutrition 0.000 claims description 6
- XFXPMWWXUTWYJX-UHFFFAOYSA-N Cyanide Chemical compound N#[C-] XFXPMWWXUTWYJX-UHFFFAOYSA-N 0.000 claims description 5
- 125000005842 heteroatom Chemical group 0.000 claims description 5
- 239000002736 nonionic surfactant Substances 0.000 claims description 5
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical class Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 claims description 4
- 229910019142 PO4 Inorganic materials 0.000 claims description 4
- 239000011668 ascorbic acid Substances 0.000 claims description 4
- 239000002585 base Substances 0.000 claims description 4
- 239000003054 catalyst Substances 0.000 claims description 4
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 4
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 4
- 229910052760 oxygen Inorganic materials 0.000 claims description 4
- 239000001301 oxygen Substances 0.000 claims description 4
- 235000021317 phosphate Nutrition 0.000 claims description 4
- 159000000000 sodium salts Chemical class 0.000 claims description 4
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical class CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 claims description 4
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims description 3
- 229940072107 ascorbate Drugs 0.000 claims description 3
- 125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 claims description 3
- 150000001860 citric acid derivatives Chemical class 0.000 claims description 3
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 3
- 239000003937 drug carrier Substances 0.000 claims description 3
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 3
- 238000007911 parenteral administration Methods 0.000 claims description 3
- 239000008194 pharmaceutical composition Substances 0.000 claims description 3
- 229910052717 sulfur Inorganic materials 0.000 claims description 3
- KJZMOBOLBHKEDP-VKMGZQQJSA-N (3S,5S,8S,9S,10R,13S,14S,17S)-17-(2-azidoacetyl)-3-hydroxy-10,13-dimethyl-3,4,5,6,7,8,9,12,14,15,16,17-dodecahydrocyclopenta[a]phenanthren-11-one Chemical compound N(=[N+]=[N-])CC([C@H]1CC[C@H]2[C@@H]3CC[C@H]4C[C@@H](C=C[C@]4(C)[C@H]3C(C[C@]12C)=O)O)=O KJZMOBOLBHKEDP-VKMGZQQJSA-N 0.000 claims description 2
- XAYWMQBOIAUHKR-LXXYRDMSSA-N 2-azido-1-[(2S,3S,5S,8R,9S,10S,13S,14S,17S)-3-hydroxy-2-methoxy-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl]ethanone Chemical compound N(=[N+]=[N-])CC([C@H]1CC[C@H]2[C@@H]3CC[C@H]4C[C@@H]([C@H](C[C@]4(C)[C@H]3CC[C@]12C)OC)O)=O XAYWMQBOIAUHKR-LXXYRDMSSA-N 0.000 claims description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 claims description 2
- 150000000994 L-ascorbates Chemical class 0.000 claims description 2
- 150000001242 acetic acid derivatives Chemical class 0.000 claims description 2
- CREXVNNSNOKDHW-UHFFFAOYSA-N azaniumylideneazanide Chemical group N[N] CREXVNNSNOKDHW-UHFFFAOYSA-N 0.000 claims description 2
- 239000003795 chemical substances by application Substances 0.000 claims description 2
- 150000003840 hydrochlorides Chemical class 0.000 claims description 2
- 229910052741 iridium Inorganic materials 0.000 claims description 2
- GKOZUEZYRPOHIO-UHFFFAOYSA-N iridium atom Chemical compound [Ir] GKOZUEZYRPOHIO-UHFFFAOYSA-N 0.000 claims description 2
- 150000003893 lactate salts Chemical class 0.000 claims description 2
- 150000002688 maleic acid derivatives Chemical class 0.000 claims description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-M methanesulfonate group Chemical class CS(=O)(=O)[O-] AFVFQIVMOAPDHO-UHFFFAOYSA-M 0.000 claims description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 claims description 2
- 239000010452 phosphate Substances 0.000 claims description 2
- 150000003013 phosphoric acid derivatives Chemical class 0.000 claims description 2
- JWMFYGXQPXQEEM-WZBAXQLOSA-N pregnane Chemical compound C1CC2CCCC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H](CC)[C@@]1(C)CC2 JWMFYGXQPXQEEM-WZBAXQLOSA-N 0.000 claims description 2
- 150000003890 succinate salts Chemical class 0.000 claims description 2
- 150000003467 sulfuric acid derivatives Chemical class 0.000 claims description 2
- 150000003892 tartrate salts Chemical class 0.000 claims description 2
- BZKVXAPAPXXTSQ-VKMGZQQJSA-N (3R,5S,8S,9S,10S,13S,14S,17S)-17-(2-azidoacetyl)-3-hydroxy-10,13-dimethyl-1,2,3,4,5,6,7,8,9,12,14,15,16,17-tetradecahydrocyclopenta[a]phenanthren-11-one Chemical compound N(=[N+]=[N-])CC([C@H]1CC[C@H]2[C@@H]3CC[C@H]4C[C@@H](CC[C@]4(C)[C@H]3C(C[C@]12C)=O)O)=O BZKVXAPAPXXTSQ-VKMGZQQJSA-N 0.000 claims 1
- UYMHSTKFRWNSPD-KHVRFEDJSA-N 3-[(2S,3S,5S,8S,9S,10S,13S,14S,17S)-3-hydroxy-10,13-dimethyl-11-oxo-2-propan-2-yloxy-1,2,3,4,5,6,7,8,9,12,14,15,16,17-tetradecahydrocyclopenta[a]phenanthren-17-yl]-3-oxopropanenitrile Chemical compound C(#N)CC([C@H]1CC[C@H]2[C@@H]3CC[C@H]4C[C@@H]([C@H](C[C@]4(C)[C@H]3C(C[C@]12C)=O)OC(C)C)O)=O UYMHSTKFRWNSPD-KHVRFEDJSA-N 0.000 claims 1
- MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 claims 1
- 150000001805 chlorine compounds Chemical class 0.000 claims 1
- 239000008024 pharmaceutical diluent Substances 0.000 claims 1
- 125000004434 sulfur atom Chemical group 0.000 claims 1
- 239000000243 solution Substances 0.000 description 140
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 106
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 87
- 150000001875 compounds Chemical class 0.000 description 80
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 68
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 63
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 62
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 60
- 235000019439 ethyl acetate Nutrition 0.000 description 22
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 21
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 21
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 20
- 239000006260 foam Substances 0.000 description 19
- 239000004094 surface-active agent Substances 0.000 description 19
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 18
- 238000012746 preparative thin layer chromatography Methods 0.000 description 18
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 17
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 15
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 14
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 14
- 239000007864 aqueous solution Substances 0.000 description 13
- 239000007787 solid Substances 0.000 description 13
- 125000004432 carbon atom Chemical group C* 0.000 description 12
- 238000001914 filtration Methods 0.000 description 12
- 238000010992 reflux Methods 0.000 description 12
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 11
- 239000012153 distilled water Substances 0.000 description 11
- 239000012044 organic layer Substances 0.000 description 11
- 239000000047 product Substances 0.000 description 11
- 239000011734 sodium Substances 0.000 description 11
- 239000000706 filtrate Substances 0.000 description 10
- 239000003208 petroleum Substances 0.000 description 10
- 239000002904 solvent Substances 0.000 description 10
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 9
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 9
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 9
- 125000000217 alkyl group Chemical group 0.000 description 9
- 239000003193 general anesthetic agent Substances 0.000 description 9
- 238000002360 preparation method Methods 0.000 description 9
- 239000011541 reaction mixture Substances 0.000 description 9
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 9
- 206010002091 Anaesthesia Diseases 0.000 description 8
- 230000037005 anaesthesia Effects 0.000 description 8
- 229940035674 anesthetics Drugs 0.000 description 8
- VTYYLEPIZMXCLO-UHFFFAOYSA-L calcium carbonate Substances [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 8
- 239000000284 extract Substances 0.000 description 8
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 7
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 7
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 7
- 238000002844 melting Methods 0.000 description 7
- 230000008018 melting Effects 0.000 description 7
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 7
- 239000002244 precipitate Substances 0.000 description 7
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- 125000006353 oxyethylene group Chemical group 0.000 description 5
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 5
- 239000011780 sodium chloride Substances 0.000 description 5
- 229910052938 sodium sulfate Inorganic materials 0.000 description 5
- 235000011152 sodium sulphate Nutrition 0.000 description 5
- 239000007858 starting material Substances 0.000 description 5
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 4
- 229920002685 Polyoxyl 35CastorOil Polymers 0.000 description 4
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- 229960000583 acetic acid Drugs 0.000 description 4
- 125000004423 acyloxy group Chemical group 0.000 description 4
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- 238000002425 crystallisation Methods 0.000 description 4
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- 230000000694 effects Effects 0.000 description 4
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 4
- QUANRIQJNFHVEU-UHFFFAOYSA-N oxirane;propane-1,2,3-triol Chemical compound C1CO1.OCC(O)CO QUANRIQJNFHVEU-UHFFFAOYSA-N 0.000 description 4
- 239000008389 polyethoxylated castor oil Substances 0.000 description 4
- KMUONIBRACKNSN-UHFFFAOYSA-N potassium dichromate Chemical compound [K+].[K+].[O-][Cr](=O)(=O)O[Cr]([O-])(=O)=O KMUONIBRACKNSN-UHFFFAOYSA-N 0.000 description 4
- 235000017557 sodium bicarbonate Nutrition 0.000 description 4
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 4
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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 3
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- 125000001309 chloro group Chemical group Cl* 0.000 description 3
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- 125000000753 cycloalkyl group Chemical group 0.000 description 3
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- 125000005843 halogen group Chemical group 0.000 description 3
- 238000010438 heat treatment Methods 0.000 description 3
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 3
- 229910052744 lithium Inorganic materials 0.000 description 3
- 239000002609 medium Substances 0.000 description 3
- 150000002825 nitriles Chemical class 0.000 description 3
- 125000004043 oxo group Chemical group O=* 0.000 description 3
- NNFCIKHAZHQZJG-UHFFFAOYSA-N potassium cyanide Chemical compound [K+].N#[C-] NNFCIKHAZHQZJG-UHFFFAOYSA-N 0.000 description 3
- 238000000746 purification Methods 0.000 description 3
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- 238000004809 thin layer chromatography Methods 0.000 description 3
- CYTQBVOFDCPGCX-UHFFFAOYSA-N trimethyl phosphite Chemical compound COP(OC)OC CYTQBVOFDCPGCX-UHFFFAOYSA-N 0.000 description 3
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- FFHIDSRFKNEHDS-NKYVDBPTSA-N (5s,8s,9s,10s,13s,14s,17s)-10,13-dimethyl-17-(2-morpholin-4-ylacetyl)-2,4,5,6,7,8,9,12,14,15,16,17-dodecahydro-1h-cyclopenta[a]phenanthrene-3,11-dione Chemical compound O=C([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(CCC(=O)C[C@@H]4CC3)C)C(=O)C[C@@]21C)CN1CCOCC1 FFHIDSRFKNEHDS-NKYVDBPTSA-N 0.000 description 2
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- UUXAGRWHGXAWCC-GDYGHMJCSA-N 2-azido-1-[(3R,5S,8R,9S,10S,13S,14S,17S)-3-hydroxy-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl]ethanone Chemical compound N(=[N+]=[N-])CC([C@H]1CC[C@H]2[C@@H]3CC[C@H]4C[C@@H](CC[C@]4(C)[C@H]3CC[C@]12C)O)=O UUXAGRWHGXAWCC-GDYGHMJCSA-N 0.000 description 2
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- 125000003710 aryl alkyl group Chemical group 0.000 description 2
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- JHIVVAPYMSGYDF-UHFFFAOYSA-N cyclohexanone Chemical compound O=C1CCCCC1 JHIVVAPYMSGYDF-UHFFFAOYSA-N 0.000 description 2
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- 150000008282 halocarbons Chemical class 0.000 description 2
- 229910052736 halogen Inorganic materials 0.000 description 2
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- LELOWRISYMNNSU-UHFFFAOYSA-N hydrogen cyanide Chemical compound N#C LELOWRISYMNNSU-UHFFFAOYSA-N 0.000 description 2
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- 150000004965 peroxy acids Chemical class 0.000 description 1
- 239000000575 pesticide Substances 0.000 description 1
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 150000003904 phospholipids Chemical class 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- 239000002798 polar solvent Substances 0.000 description 1
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
- 235000010483 polyoxyethylene sorbitan monopalmitate Nutrition 0.000 description 1
- 239000000249 polyoxyethylene sorbitan monopalmitate Substances 0.000 description 1
- 239000001818 polyoxyethylene sorbitan monostearate Substances 0.000 description 1
- 235000010989 polyoxyethylene sorbitan monostearate Nutrition 0.000 description 1
- 229920000136 polysorbate Polymers 0.000 description 1
- 229920000053 polysorbate 80 Polymers 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 235000015497 potassium bicarbonate Nutrition 0.000 description 1
- 229910000028 potassium bicarbonate Inorganic materials 0.000 description 1
- 239000011736 potassium bicarbonate Substances 0.000 description 1
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 150000003128 pregnanes Chemical class 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 229940107700 pyruvic acid Drugs 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 150000003335 secondary amines Chemical class 0.000 description 1
- 125000000467 secondary amino group Chemical group [H]N([*:1])[*:2] 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 230000000707 stereoselective effect Effects 0.000 description 1
- 239000008174 sterile solution Substances 0.000 description 1
- 239000012258 stirred mixture Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 125000000446 sulfanediyl group Chemical group *S* 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 125000004213 tert-butoxy group Chemical group [H]C([H])([H])C(O*)(C([H])([H])[H])C([H])([H])[H] 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
- 150000003512 tertiary amines Chemical class 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
- 125000000858 thiocyanato group Chemical group *SC#N 0.000 description 1
- 150000003573 thiols Chemical class 0.000 description 1
- AWLILQARPMWUHA-UHFFFAOYSA-M thiopental sodium Chemical compound [Na+].CCCC(C)C1(CC)C(=O)NC([S-])=NC1=O AWLILQARPMWUHA-UHFFFAOYSA-M 0.000 description 1
- 201000005060 thrombophlebitis Diseases 0.000 description 1
- 125000005424 tosyloxy group Chemical group S(=O)(=O)(C1=CC=C(C)C=C1)O* 0.000 description 1
- 125000005457 triglyceride group Chemical group 0.000 description 1
- 235000013343 vitamin Nutrition 0.000 description 1
- 239000011782 vitamin Substances 0.000 description 1
- 229940088594 vitamin Drugs 0.000 description 1
- 229930003231 vitamin Natural products 0.000 description 1
- 150000003722 vitamin derivatives Chemical class 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D265/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom and one oxygen atom as the only ring hetero atoms
- C07D265/28—1,4-Oxazines; Hydrogenated 1,4-oxazines
- C07D265/30—1,4-Oxazines; Hydrogenated 1,4-oxazines not condensed with other rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J5/00—Normal steroids containing carbon, hydrogen, halogen or oxygen, substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane and substituted in position 21 by only one singly bound oxygen atom, i.e. only one oxygen bound to position 21 by a single bond
- C07J5/0007—Normal steroids containing carbon, hydrogen, halogen or oxygen, substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane and substituted in position 21 by only one singly bound oxygen atom, i.e. only one oxygen bound to position 21 by a single bond not substituted in position 17 alfa
- C07J5/0015—Normal steroids containing carbon, hydrogen, halogen or oxygen, substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane and substituted in position 21 by only one singly bound oxygen atom, i.e. only one oxygen bound to position 21 by a single bond not substituted in position 17 alfa not substituted in position 16
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J41/00—Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring
- C07J41/0033—Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring not covered by C07J41/0005
- C07J41/005—Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring not covered by C07J41/0005 the 17-beta position being substituted by an uninterrupted chain of only two carbon atoms, e.g. pregnane derivatives
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J41/00—Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring
- C07J41/0033—Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring not covered by C07J41/0005
- C07J41/0094—Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring not covered by C07J41/0005 containing nitrile radicals, including thiocyanide radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J7/00—Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of two carbon atoms
- C07J7/008—Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of two carbon atoms substituted in position 21
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J7/00—Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of two carbon atoms
- C07J7/008—Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of two carbon atoms substituted in position 21
- C07J7/0085—Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of two carbon atoms substituted in position 21 by an halogen atom
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Toxicology (AREA)
- Steroid Compounds (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB2114272A GB1430942A (en) | 1972-05-05 | 1972-05-05 | 21-substituted 3alpha-hydroxy pregnanes |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DE2322532A1 true DE2322532A1 (de) | 1973-11-22 |
Family
ID=10157915
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE2322532A Ceased DE2322532A1 (de) | 1972-05-05 | 1973-05-04 | Pregnanderivate und verfahren zu ihrer herstellung |
Country Status (16)
| Country | Link |
|---|---|
| JP (1) | JPS4961150A (en:Method) |
| AT (1) | AT355232B (en:Method) |
| AU (1) | AU475168B2 (en:Method) |
| BE (1) | BE799102A (en:Method) |
| CA (1) | CA1013341A (en:Method) |
| CH (1) | CH617710A5 (en:Method) |
| DE (1) | DE2322532A1 (en:Method) |
| ES (1) | ES414411A1 (en:Method) |
| FR (1) | FR2183792B1 (en:Method) |
| GB (1) | GB1430942A (en:Method) |
| IE (1) | IE37596B1 (en:Method) |
| IL (1) | IL42196A (en:Method) |
| LU (1) | LU67546A1 (en:Method) |
| NL (1) | NL7306234A (en:Method) |
| SE (1) | SE400771B (en:Method) |
| ZA (1) | ZA733035B (en:Method) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5591733A (en) * | 1987-08-25 | 1997-01-07 | University Of Southern California | Methods, compositions, and compounds for allosteric modulation of the gaba receptor by members of the androstane and pregnane series |
Families Citing this family (24)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5939545A (en) * | 1994-02-14 | 1999-08-17 | Cocensys, Inc. | Method, compositions, and compounds for allosteric modulation of the gaba receptor by members of the androstane and pregnane series |
| WO1995021617A1 (en) * | 1994-02-14 | 1995-08-17 | Cocensys, Inc. | Androstanes and pregnanes for allosteric modulation of gaba receptor |
| GR1003861B (el) * | 2000-12-29 | 2002-04-11 | Νεα νευροστεροειδη που αλληλεπιδρουν με τον υποδοχεα gabaa. | |
| JP4915427B2 (ja) * | 2009-03-30 | 2012-04-11 | ブラザー工業株式会社 | 液体供給ジョイント、これを使用した液体吐出ヘッド及び記録装置 |
| AU2012323888A1 (en) | 2011-10-14 | 2014-05-29 | Sage Therapeutics, Inc. | 3,3 disubstituted 19-nor pregnane compounds, compositions, and uses thereof |
| MX2014008895A (es) | 2012-01-23 | 2014-11-25 | Sage Therapeutics Inc | Formulaciones de esteroides neuroactivos y metodos para tratar trastornos del cns. |
| IL294306B2 (en) | 2012-08-21 | 2024-01-01 | Sage Therapeutics Inc | Treatment methods for epilepsy and status epilepticus |
| WO2014169836A1 (en) | 2013-04-17 | 2014-10-23 | Sage Therapeutics, Inc. | 19-nor neuroactive steroids and methods of use thereof |
| SI3498725T1 (sl) | 2013-04-17 | 2021-11-30 | Sage Therapeutics, Inc. | 19-NOR C3,3-disubstituiran C21-N-pirazolilni steroid za uporabo v terapiji |
| JP6239091B2 (ja) | 2013-04-17 | 2017-11-29 | セージ セラピューティクス， インコーポレイテッド | １９−ノル神経刺激性ステロイドおよびその使用方法 |
| WO2014169831A1 (en) | 2013-04-17 | 2014-10-23 | Sage Therapeutics, Inc. | 19-nor c3,3-disubstituted c21-c-bound heteroaryl steroids and methods of use thereof |
| CA2918735C (en) | 2013-07-19 | 2023-08-01 | Sage Therapeutics, Inc. | Neuroactive steroids, compositions, and uses thereof |
| EP3035940B1 (en) | 2013-08-23 | 2018-10-17 | Sage Therapeutics, Inc. | Neuroactive steroids, compositions, and uses thereof |
| WO2015195962A1 (en) | 2014-06-18 | 2015-12-23 | Sage Therapeutics, Inc. | Neuroactive steroids, compositions, and uses thereof |
| JOP20200195A1 (ar) | 2014-09-08 | 2017-06-16 | Sage Therapeutics Inc | سترويدات وتركيبات نشطة عصبياً، واستخداماتها |
| MX2021004492A (es) | 2014-10-16 | 2022-12-05 | Sage Therapeutics Inc | Composiciones para el tratamiento de trastornos del snc. |
| HRP20201216T1 (hr) | 2014-10-16 | 2020-12-11 | Sage Therapeutics, Inc. | PRIPRAVCI I POSTUPCI ZA LIJEČENJE POREMEĆAJA CNS-a |
| JP6893173B2 (ja) | 2014-11-27 | 2021-06-23 | セージ セラピューティクス， インコーポレイテッド | Ｃｎｓ障害を処置するための組成物および方法 |
| PL3250210T3 (pl) | 2015-01-26 | 2021-07-26 | Sage Therapeutics, Inc. | Kompozycje i sposoby leczenia zaburzeń OUN |
| JP6875996B2 (ja) | 2015-02-20 | 2021-05-26 | セージ セラピューティクス， インコーポレイテッド | 神経刺激性ステロイド、組成物、およびその使用 |
| RU2766155C2 (ru) | 2016-03-08 | 2022-02-08 | Сейдж Терапьютикс, Инк. | Нейроактивные стероиды, их композиции и применения |
| CA3030420A1 (en) | 2016-07-11 | 2018-01-18 | Sage Therapeutics, Inc. | C7, c12, and c16 substituted neuroactive steroids and their methods of use |
| JP7049313B2 (ja) | 2016-07-11 | 2022-04-06 | セージ セラピューティクス， インコーポレイテッド | Ｃ１７、ｃ２０、およびｃ２１置換神経刺激性ステロイドおよびそれらの使用方法 |
| WO2020243488A1 (en) | 2019-05-31 | 2020-12-03 | Sage Therapeutics, Inc. | Neuroactive steroids and compositions thereof |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR1346292A (fr) * | 1962-09-14 | 1963-12-20 | Roussel Uclaf | Nouveau procédé de préparation des 21-amino stéroïdes |
| US3144446A (en) * | 1963-12-20 | 1964-08-11 | Upjohn Co | Mono and bis nu-(3alpha, 17alpha-dihydroxy-11, 20-dioxo-5beta-pregnan-21-yl) quaternary ammonium salts of triethylenediamine |
-
1972
- 1972-05-05 GB GB2114272A patent/GB1430942A/en not_active Expired
-
1973
- 1973-05-04 CA CA170,482A patent/CA1013341A/en not_active Expired
- 1973-05-04 BE BE130749A patent/BE799102A/xx unknown
- 1973-05-04 DE DE2322532A patent/DE2322532A1/de not_active Ceased
- 1973-05-04 AU AU55284/73A patent/AU475168B2/en not_active Expired
- 1973-05-04 ZA ZA733035A patent/ZA733035B/xx unknown
- 1973-05-04 AT AT395173A patent/AT355232B/de not_active IP Right Cessation
- 1973-05-04 ES ES0414411A patent/ES414411A1/es not_active Expired
- 1973-05-04 CH CH636073A patent/CH617710A5/de not_active IP Right Cessation
- 1973-05-04 IE IE709/73A patent/IE37596B1/xx unknown
- 1973-05-04 FR FR7316108A patent/FR2183792B1/fr not_active Expired
- 1973-05-04 IL IL42196A patent/IL42196A/xx unknown
- 1973-05-04 SE SE7306330A patent/SE400771B/xx unknown
- 1973-05-04 LU LU67546A patent/LU67546A1/xx unknown
- 1973-05-04 JP JP48050183A patent/JPS4961150A/ja active Pending
- 1973-05-04 NL NL7306234A patent/NL7306234A/xx not_active Application Discontinuation
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5591733A (en) * | 1987-08-25 | 1997-01-07 | University Of Southern California | Methods, compositions, and compounds for allosteric modulation of the gaba receptor by members of the androstane and pregnane series |
Also Published As
| Publication number | Publication date |
|---|---|
| JPS4961150A (en:Method) | 1974-06-13 |
| IE37596B1 (en) | 1977-08-31 |
| FR2183792B1 (en:Method) | 1977-07-15 |
| CA1013341A (en) | 1977-07-05 |
| SE400771B (sv) | 1978-04-10 |
| BE799102A (fr) | 1973-11-05 |
| ES414411A1 (es) | 1976-02-01 |
| IL42196A (en) | 1978-10-31 |
| CH617710A5 (en) | 1980-06-13 |
| GB1430942A (en) | 1976-04-07 |
| AU475168B2 (en) | 1976-08-12 |
| ZA733035B (en) | 1974-04-24 |
| FR2183792A1 (en:Method) | 1973-12-21 |
| IE37596L (en) | 1973-11-05 |
| AT355232B (de) | 1980-02-25 |
| ATA395173A (de) | 1979-07-15 |
| NL7306234A (en:Method) | 1973-11-07 |
| AU5528473A (en) | 1974-11-07 |
| IL42196A0 (en) | 1973-07-30 |
| LU67546A1 (en:Method) | 1973-07-13 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| OD | Request for examination | ||
| 8131 | Rejection |