NO791141L - 17beta-tiokarboksylsyreestere av 4-halogen-3-oksyandrost-4-enes, og fremgangsmaate til deres fremstilling - Google Patents

17beta-tiokarboksylsyreestere av 4-halogen-3-oksyandrost-4-enes, og fremgangsmaate til deres fremstilling

Info

Publication number: NO791141L
Authority: NO; Norway
Prior art keywords: methyl; fluorine; diene; hydroxy; hydrogen
Prior art date: 1978-04-05

Application number

NO791141A

Other languages

English (en)

Norwegian (no)

Inventor

Francisco S Alvarez

Original Assignee

Syntex Inc

Priority date (The priority date 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 date listed.)

1978-04-05

Filing date

1979-04-04

Publication date

1979-10-08

1979-04-04 Application filed by Syntex Inc filed Critical Syntex Inc

1979-10-08 Publication of NO791141L publication Critical patent/NO791141L/no

Links

238000000034 method Methods 0.000 title claims abstract description 71
238000002360 preparation method Methods 0.000 title claims abstract description 46
230000008569 process Effects 0.000 claims abstract description 10
150000001875 compounds Chemical class 0.000 claims description 125
239000011737 fluorine Substances 0.000 claims description 51
229910052731 fluorine Inorganic materials 0.000 claims description 51
239000000460 chlorine Substances 0.000 claims description 44
239000001257 hydrogen Substances 0.000 claims description 44
229910052739 hydrogen Inorganic materials 0.000 claims description 44
229910052801 chlorine Inorganic materials 0.000 claims description 42
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 40
125000000217 alkyl group Chemical group 0.000 claims description 40
125000004432 carbon atom Chemical group C* 0.000 claims description 30
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 25
238000004519 manufacturing process Methods 0.000 claims description 23
-1 isopropylidenedioxy Chemical group 0.000 claims description 21
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 20
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 20
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 19
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 19
229910052794 bromium Inorganic materials 0.000 claims description 19
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 18
230000003110 anti-inflammatory effect Effects 0.000 claims description 14
125000001153 fluoro group Chemical group F* 0.000 claims description 11
125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 9
125000001424 substituent group Chemical group 0.000 claims description 6
241000124008 Mammalia Species 0.000 claims description 5
229910052736 halogen Inorganic materials 0.000 claims description 5
150000002367 halogens Chemical class 0.000 claims description 5
125000003545 alkoxy group Chemical group 0.000 claims description 4
239000008024 pharmaceutical diluent Substances 0.000 claims description 4
239000000825 pharmaceutical preparation Substances 0.000 claims description 4
125000001309 chloro group Chemical group Cl* 0.000 claims description 3
150000001447 alkali salts Chemical class 0.000 claims description 2
YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 claims 11
125000001589 carboacyl group Chemical group 0.000 claims 4
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 84
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 59
239000000203 mixture Substances 0.000 description 57
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 42
238000006243 chemical reaction Methods 0.000 description 37
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 29
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical group CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 28
WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 27
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 27
239000002904 solvent Substances 0.000 description 24
239000000243 solution Substances 0.000 description 22
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 20
150000003431 steroids Chemical class 0.000 description 19
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 18
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 18
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 18
239000002244 precipitate Substances 0.000 description 17
239000007858 starting material Substances 0.000 description 17
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 16
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 15
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 14
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 13
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 13
JYGXADMDTFJGBT-VWUMJDOOSA-N hydrocortisone Chemical compound O=C1CC[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 JYGXADMDTFJGBT-VWUMJDOOSA-N 0.000 description 12
239000000047 product Substances 0.000 description 12
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 11
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 11
125000002252 acyl group Chemical group 0.000 description 10
150000002431 hydrogen Chemical class 0.000 description 10
229910000027 potassium carbonate Inorganic materials 0.000 description 10
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 9
QMMFVYPAHWMCMS-UHFFFAOYSA-N Dimethyl sulfide Chemical compound CSC QMMFVYPAHWMCMS-UHFFFAOYSA-N 0.000 description 9
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 9
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 9
XHFXMNZYIKFCPN-UHFFFAOYSA-N perchloryl fluoride Chemical compound FCl(=O)(=O)=O XHFXMNZYIKFCPN-UHFFFAOYSA-N 0.000 description 9
238000004809 thin layer chromatography Methods 0.000 description 9
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 8
238000002844 melting Methods 0.000 description 8
230000008018 melting Effects 0.000 description 8
239000002674 ointment Substances 0.000 description 8
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 8
PYOKUURKVVELLB-UHFFFAOYSA-N trimethyl orthoformate Chemical compound COC(OC)OC PYOKUURKVVELLB-UHFFFAOYSA-N 0.000 description 8
ZKLFRQSZDUSMQE-UHFFFAOYSA-N 5,5-dichloroimidazolidine-2,4-dione Chemical compound ClC1(Cl)NC(=O)NC1=O ZKLFRQSZDUSMQE-UHFFFAOYSA-N 0.000 description 7
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 7
150000008064 anhydrides Chemical class 0.000 description 7
229960000890 hydrocortisone Drugs 0.000 description 7
229910052757 nitrogen Inorganic materials 0.000 description 7
WYVAMUWZEOHJOQ-UHFFFAOYSA-N propionic anhydride Chemical compound CCC(=O)OC(=O)CC WYVAMUWZEOHJOQ-UHFFFAOYSA-N 0.000 description 7
CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 6
PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 6
DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 6
RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 6
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 6
229910052799 carbon Inorganic materials 0.000 description 6
230000000694 effects Effects 0.000 description 6
229960001347 fluocinolone acetonide Drugs 0.000 description 6
FEBLZLNTKCEFIT-VSXGLTOVSA-N fluocinolone acetonide Chemical compound C1([C@@H](F)C2)=CC(=O)C=C[C@]1(C)[C@]1(F)[C@@H]2[C@@H]2C[C@H]3OC(C)(C)O[C@@]3(C(=O)CO)[C@@]2(C)C[C@@H]1O FEBLZLNTKCEFIT-VSXGLTOVSA-N 0.000 description 6
239000001301 oxygen Substances 0.000 description 6
229910052760 oxygen Inorganic materials 0.000 description 6
239000011541 reaction mixture Substances 0.000 description 6
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 5
239000005864 Sulphur Substances 0.000 description 5
229960000583 acetic acid Drugs 0.000 description 5
239000002253 acid Substances 0.000 description 5
LUFPJJNWMYZRQE-UHFFFAOYSA-N benzylsulfanylmethylbenzene Chemical compound C=1C=CC=CC=1CSCC1=CC=CC=C1 LUFPJJNWMYZRQE-UHFFFAOYSA-N 0.000 description 5
239000006071 cream Substances 0.000 description 5
LGTLXDJOAJDFLR-UHFFFAOYSA-N diethyl chlorophosphate Chemical compound CCOP(Cl)(=O)OCC LGTLXDJOAJDFLR-UHFFFAOYSA-N 0.000 description 5
238000005658 halogenation reaction Methods 0.000 description 5
RUOJZAUFBMNUDX-UHFFFAOYSA-N propylene carbonate Chemical compound CC1COC(=O)O1 RUOJZAUFBMNUDX-UHFFFAOYSA-N 0.000 description 5
239000000741 silica gel Substances 0.000 description 5
229910002027 silica gel Inorganic materials 0.000 description 5
239000007787 solid Substances 0.000 description 5
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 4
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 4
LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 4
238000004458 analytical method Methods 0.000 description 4
239000003085 diluting agent Substances 0.000 description 4
239000012362 glacial acetic acid Substances 0.000 description 4
230000026030 halogenation Effects 0.000 description 4
238000001953 recrystallisation Methods 0.000 description 4
238000003756 stirring Methods 0.000 description 4
HIFJUMGIHIZEPX-UHFFFAOYSA-N sulfuric acid;sulfur trioxide Chemical compound O=S(=O)=O.OS(O)(=O)=O HIFJUMGIHIZEPX-UHFFFAOYSA-N 0.000 description 4
230000000699 topical effect Effects 0.000 description 4
LKQVYBSBDWEBEM-VMXHOPILSA-N (8s,9s,10r,13s,14s)-10,13-dimethyl-6,7,8,9,11,12,14,15,16,17-decahydro-3h-cyclopenta[a]phenanthrene Chemical class C1CC2=CCC=C[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CCC[C@@]1(C)CC2 LKQVYBSBDWEBEM-VMXHOPILSA-N 0.000 description 3
OFQCQIGMURIECL-UHFFFAOYSA-N 2-[2-(diethylamino)ethyl]-2',6'-dimethylspiro[isoquinoline-4,4'-oxane]-1,3-dione;phosphoric acid Chemical compound OP(O)(O)=O.O=C1N(CCN(CC)CC)C(=O)C2=CC=CC=C2C21CC(C)OC(C)C2 OFQCQIGMURIECL-UHFFFAOYSA-N 0.000 description 3
MENYRYNFSIBDQN-UHFFFAOYSA-N 5,5-dibromoimidazolidine-2,4-dione Chemical compound BrC1(Br)NC(=O)NC1=O MENYRYNFSIBDQN-UHFFFAOYSA-N 0.000 description 3
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 3
241001465754 Metazoa Species 0.000 description 3
HYRKAAMZBDSJFJ-LFDBJOOHSA-N Paramethasone acetate Chemical compound C1([C@@H](F)C2)=CC(=O)C=C[C@]1(C)[C@@H]1[C@@H]2[C@@H]2C[C@@H](C)[C@@](C(=O)COC(C)=O)(O)[C@@]2(C)C[C@@H]1O HYRKAAMZBDSJFJ-LFDBJOOHSA-N 0.000 description 3
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 3
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239000000654 additive Substances 0.000 description 3
229910052783 alkali metal Inorganic materials 0.000 description 3
239000002585 base Substances 0.000 description 3
LTYMSROWYAPPGB-UHFFFAOYSA-N diphenyl sulfide Chemical class C=1C=CC=CC=1SC1=CC=CC=C1 LTYMSROWYAPPGB-UHFFFAOYSA-N 0.000 description 3
230000008030 elimination Effects 0.000 description 3
238000003379 elimination reaction Methods 0.000 description 3
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239000000706 filtrate Substances 0.000 description 3
210000000245 forearm Anatomy 0.000 description 3
230000009931 harmful effect Effects 0.000 description 3
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230000002757 inflammatory effect Effects 0.000 description 3
239000000543 intermediate Substances 0.000 description 3
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229960002858 paramethasone Drugs 0.000 description 3
DUCKXCGALKOSJF-UHFFFAOYSA-N pentanoyl pentanoate Chemical compound CCCCC(=O)OC(=O)CCCC DUCKXCGALKOSJF-UHFFFAOYSA-N 0.000 description 3
229960005205 prednisolone Drugs 0.000 description 3
238000010992 reflux Methods 0.000 description 3
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235000011152 sodium sulphate Nutrition 0.000 description 3
239000000126 substance Substances 0.000 description 3
239000004094 surface-active agent Substances 0.000 description 3
230000003096 thymolvtic effect Effects 0.000 description 3
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IATKKATWPOVYCC-VMXHOPILSA-N (8s,9s,10r,13s,14s)-10,13-dimethyl-2,3,6,7,8,9,11,12,14,15,16,17-dodecahydro-1h-cyclopenta[a]phenanthrene Chemical class C1CC2=CCCC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CCC[C@@]1(C)CC2 IATKKATWPOVYCC-VMXHOPILSA-N 0.000 description 2
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HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 2
KRHYYFGTRYWZRS-UHFFFAOYSA-N Fluorane Chemical compound F KRHYYFGTRYWZRS-UHFFFAOYSA-N 0.000 description 2
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 2
241000699666 Mus <mouse, genus> Species 0.000 description 2
241000699670 Mus sp. Species 0.000 description 2
JRNVZBWKYDBUCA-UHFFFAOYSA-N N-chlorosuccinimide Chemical compound ClN1C(=O)CCC1=O JRNVZBWKYDBUCA-UHFFFAOYSA-N 0.000 description 2
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206010047139 Vasoconstriction Diseases 0.000 description 2
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150000001412 amines Chemical class 0.000 description 2
239000003963 antioxidant agent Substances 0.000 description 2
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238000010586 diagram Methods 0.000 description 2
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PKHMTIRCAFTBDS-UHFFFAOYSA-N hexanoyl hexanoate Chemical compound CCCCCC(=O)OC(=O)CCCCC PKHMTIRCAFTBDS-UHFFFAOYSA-N 0.000 description 2
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WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 2
239000012442 inert solvent Substances 0.000 description 2
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
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QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 2
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PSHKMPUSSFXUIA-UHFFFAOYSA-N n,n-dimethylpyridin-2-amine Chemical compound CN(C)C1=CC=CC=N1 PSHKMPUSSFXUIA-UHFFFAOYSA-N 0.000 description 2
125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
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OIGNJSKKLXVSLS-VWUMJDOOSA-N prednisolone Chemical compound O=C1C=C[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 OIGNJSKKLXVSLS-VWUMJDOOSA-N 0.000 description 2
150000003254 radicals Chemical class 0.000 description 2
230000004044 response Effects 0.000 description 2
QBERHIJABFXGRZ-UHFFFAOYSA-M rhodium;triphenylphosphane;chloride Chemical compound [Cl-].[Rh].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 QBERHIJABFXGRZ-UHFFFAOYSA-M 0.000 description 2
239000000377 silicon dioxide Substances 0.000 description 2
JQWHASGSAFIOCM-UHFFFAOYSA-M sodium periodate Chemical compound [Na+].[O-]I(=O)(=O)=O JQWHASGSAFIOCM-UHFFFAOYSA-M 0.000 description 2
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229910052717 sulfur Inorganic materials 0.000 description 2
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AKEJUJNQAAGONA-UHFFFAOYSA-N sulfur trioxide Chemical compound O=S(=O)=O AKEJUJNQAAGONA-UHFFFAOYSA-N 0.000 description 2
239000000725 suspension Substances 0.000 description 2
230000009885 systemic effect Effects 0.000 description 2
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 2
230000001225 therapeutic effect Effects 0.000 description 2
GKASDNZWUGIAMG-UHFFFAOYSA-N triethyl orthoformate Chemical compound CCOC(OCC)OCC GKASDNZWUGIAMG-UHFFFAOYSA-N 0.000 description 2
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Classifications

- 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
- C07J5/0046—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 substituted in position 17 alfa
- C07J5/0061—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 substituted in position 17 alfa substituted in position 16
- C07J5/0069—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 substituted in position 17 alfa substituted in position 16 by a saturated or unsaturated hydrocarbon group
- C07J5/0076—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 substituted in position 17 alfa substituted in position 16 by a saturated or unsaturated hydrocarbon group by an alkyl group
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J3/00—Normal steroids containing carbon, hydrogen, halogen or oxygen, substituted in position 17 beta by one carbon atom
- C07J3/005—Normal steroids containing carbon, hydrogen, halogen or oxygen, substituted in position 17 beta by one carbon atom the carbon atom being part of a carboxylic function
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J31/00—Normal steroids containing one or more sulfur atoms not belonging to a hetero ring
- C07J31/006—Normal steroids containing one or more sulfur atoms not belonging to a hetero ring not covered by C07J31/003
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J71/00—Steroids in which the cyclopenta(a)hydrophenanthrene skeleton is condensed with a heterocyclic ring
- C07J71/0005—Oxygen-containing hetero ring
- C07J71/0026—Oxygen-containing hetero ring cyclic ketals
- C07J71/0031—Oxygen-containing hetero ring cyclic ketals at positions 16, 17

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
General Health & Medical Sciences (AREA)
Life Sciences & Earth Sciences (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Rheumatology (AREA)
Pharmacology & Pharmacy (AREA)
Chemical Kinetics & Catalysis (AREA)
Animal Behavior & Ethology (AREA)
Pain & Pain Management (AREA)
Public Health (AREA)
Veterinary Medicine (AREA)
Steroid Compounds (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

NO791141A 1978-04-05 1979-04-04 17beta-tiokarboksylsyreestere av 4-halogen-3-oksyandrost-4-enes, og fremgangsmaate til deres fremstilling NO791141L (no)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
US05/893,390 US4198403A (en)	1978-04-05	1978-04-05	17 Beta-thiocarboxylic acid esters of 4-halo-3-oxoandrost-4-enes

Publications (1)

Publication Number	Publication Date
NO791141L true NO791141L (no)	1979-10-08

Family

ID=25401489

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
NO791141A NO791141L (no)	1978-04-05	1979-04-04	17beta-tiokarboksylsyreestere av 4-halogen-3-oksyandrost-4-enes, og fremgangsmaate til deres fremstilling

Country Status (17)

Country	Link
US (1)	US4198403A (de)
EP (1)	EP0004773B1 (de)
JP (1)	JPS54135761A (de)
AT (1)	ATA251879A (de)
AU (1)	AU4575279A (de)
CS (2)	CS209916B2 (de)
DE (1)	DE2960292D1 (de)
DK (1)	DK136479A (de)
ES (1)	ES479272A1 (de)
FI (1)	FI791088A7 (de)
GR (1)	GR67274B (de)
IL (1)	IL56991A (de)
IT (1)	IT7967709A0 (de)
NO (1)	NO791141L (de)
PL (2)	PL118567B1 (de)
PT (1)	PT69412A (de)
ZA (1)	ZA791638B (de)

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SE8004580L (sv) *	1980-06-19	1981-12-20	Draco Ab	Farmaceutisk beredning
US4340538A (en) *	1980-07-21	1982-07-20	The Upjohn Company	Process for producing 6α-fluoro-Δ1,4 -3-keto steroids
SE8306370D0 (sv) *	1983-11-18	1983-11-18	Draco Ab	Novel androstane-17beta-carboxylic acid esters, a process and intermediates for their preparation, compositions and method for the treatment of inflammatory conditions
US4599331A (en) *	1984-12-24	1986-07-08	Syntex (U.S.A.) Inc.	Etianic acids as antiangiogenics
US5646136A (en) *	1994-01-04	1997-07-08	Duke University	Methods of inhibiting angiogenesis and tumor growth, and treating ophthalmologic conditions with angiostatic and therapeutic steroids
US5693629A (en) *	1994-04-04	1997-12-02	Meiji Milk Products Co., Ltd.	Progesterone compound and use thereof
US5981517A (en) *	1996-05-09	1999-11-09	Soft Drugs, Inc.	Androstene derivatives
US20020133032A1 (en) *	2000-02-25	2002-09-19	Jufang Barkalow	Method for the preparation of fluticasone and related 17beta-carbothioic esters using a novel carbothioic acid synthesis and novel purification methods
US20030085387A1 (en) *	2000-05-31	2003-05-08	Takahiro Fujiyama	Optical materials and optical part each containing aromatic sulfide compound and aromatic sulfide compound
EP2067784A3 (de) *	2000-08-05	2012-08-22	Glaxo Group Limited	17.beta.-Carbothioat-17.alpha.-Arylcarbonyloxyloxy-Androstan-Derivate als entzündungshemmende Mittel
US6777400B2 (en) *	2000-08-05	2004-08-17	Smithkline Beecham Corporation	Anti-inflammatory androstane derivative compositions
US6777399B2 (en) *	2000-08-05	2004-08-17	Smithkline Beecham Corporation	Anti-inflammatory androstane derivative compositions
US6858596B2 (en) *	2000-08-05	2005-02-22	Smithkline Beecham Corporation	Formulation containing anti-inflammatory androstane derivative
US6858593B2 (en) *	2000-08-05	2005-02-22	Smithkline Beecham Corporation	Anti-inflammatory androstane derivative compositions
US6787532B2 (en) *	2000-08-05	2004-09-07	Smithkline Beecham Corporation	Formulation containing anti-inflammatory androstane derivatives
US6759398B2 (en)	2000-08-05	2004-07-06	Smithkline Beecham Corporation	Anti-inflammatory androstane derivative
US6750210B2 (en) *	2000-08-05	2004-06-15	Smithkline Beecham Corporation	Formulation containing novel anti-inflammatory androstane derivative
GB0019172D0 (en) *	2000-08-05	2000-09-27	Glaxo Group Ltd	Novel compounds
UA77656C2 (en) *	2001-04-07	2007-01-15	Glaxo Group Ltd	S-fluoromethyl ester of 6-alpha, 9-alpha-difluoro-17-alpha-[(2-furanylcarbonyl)oxy]-11-beta-hydroxy-16- alpha-methyl-3-oxoandrosta-1,4-dien-17-beta-carbothioacid as anti-inflammatory agent
WO2002088167A1 (en) *	2001-04-30	2002-11-07	Glaxo Group Limited	Anti-inflammatory 17.beta.-carbothioate ester derivatives of androstane with a cyclic ester group in position 17.alpha
US20050175545A1 (en) *	2002-02-04	2005-08-11	Keith Biggadike	Formulation for inhalation comprising a glucocorticoid and a beta 2-adrenoreceptor agonist
GB0202635D0 (en) *	2002-02-05	2002-03-20	Glaxo Wellcome Mfg Pte Ltd	Formulation containing novel anti-inflammatory androstane derivative
GB2389530B (en) *	2002-06-14	2007-01-10	Cipla Ltd	Pharmaceutical compositions
CA2530680A1 (en) *	2003-04-04	2004-10-14	Alpharma Aps	Process for the preparation of steroidal carbothioic acid derivatives and intermediates
GB0507165D0 (en) *	2005-04-08	2005-05-18	Glaxo Group Ltd	Novel crystalline pharmaceutical product
GB0615108D0 (en) *	2006-07-28	2006-09-06	Glaxo Group Ltd	Novel formulations
EP2443134A2 (de)	2009-06-16	2012-04-25	Schering Corporation	Neue [3,2-c]heteroarylsteroide als glucocorticoidrezeptoragonisten, zusammensetzungen und verwendung
CN115558013B (zh) *	2021-07-02	2025-02-18	石家庄迪斯凯威医药科技有限公司	一种甾体磷酸酯化合物及其应用

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US4093721A (en) *	1974-08-30	1978-06-06	Glaxo Laboratories Limited	Pharmaceutical compositions of 6α,9α-difluoro-androst-4-ene-17β-carboxylates and derivatives thereof
CH628355A5 (de) *	1976-02-24	1982-02-26	Ciba Geigy Ag	Verfahren zur herstellung neuer androstadien-17beta-carbonsaeuren und ihrer ester und salze.

1978
- 1978-04-05 US US05/893,390 patent/US4198403A/en not_active Expired - Lifetime
1979
- 1979-03-30 PT PT69412A patent/PT69412A/pt unknown
- 1979-03-31 GR GR58747A patent/GR67274B/el unknown
- 1979-04-02 FI FI791088A patent/FI791088A7/fi not_active Application Discontinuation
- 1979-04-02 IL IL56991A patent/IL56991A/xx unknown
- 1979-04-03 DE DE7979300549T patent/DE2960292D1/de not_active Expired
- 1979-04-03 EP EP79300549A patent/EP0004773B1/de not_active Expired
- 1979-04-03 AU AU45752/79A patent/AU4575279A/en not_active Abandoned
- 1979-04-03 DK DK136579A patent/DK136479A/da unknown
- 1979-04-04 CS CS792306A patent/CS209916B2/cs unknown
- 1979-04-04 PL PL1979214675A patent/PL118567B1/pl unknown
- 1979-04-04 CS CS797273A patent/CS209919B2/cs unknown
- 1979-04-04 AT AT0251879A patent/ATA251879A/de unknown
- 1979-04-04 NO NO791141A patent/NO791141L/no unknown
- 1979-04-04 ES ES479272A patent/ES479272A1/es not_active Expired
- 1979-04-04 IT IT7967709A patent/IT7967709A0/it unknown
- 1979-04-04 PL PL1979222926A patent/PL121569B1/pl unknown
- 1979-04-05 ZA ZA791638A patent/ZA791638B/xx unknown
- 1979-04-05 JP JP4041379A patent/JPS54135761A/ja active Pending

Also Published As

Publication number	Publication date
CS209916B2 (en)	1981-12-31
CS209919B2 (en)	1981-12-31
DK136479A (da)	1979-10-06
PT69412A (en)	1979-04-01
ATA251879A (de)	1982-04-15
PL222926A1 (de)	1981-01-02
ZA791638B (en)	1980-11-26
DE2960292D1 (en)	1981-08-06
PL214675A1 (de)	1980-07-28
GR67274B (de)	1981-06-26
PL118567B1 (en)	1981-10-31
ES479272A1 (es)	1980-01-16
AU4575279A (en)	1979-10-11
FI791088A7 (fi)	1981-01-01
IT7967709A0 (it)	1979-04-04
PL121569B1 (en)	1982-05-31
IL56991A0 (en)	1979-07-25
EP0004773B1 (de)	1981-04-29
EP0004773A2 (de)	1979-10-17
US4198403A (en)	1980-04-15
EP0004773A3 (en)	1979-10-31
IL56991A (en)	1982-01-31
JPS54135761A (en)	1979-10-22

Publication	Publication Date	Title
EP0004773B1 (de)	1981-04-29	4-Halo-3-oxo-androst-4-en-17beta-thiocarbonsäureester, ihre pharmazeutische Anwendung und Verfahren zu ihrer Herstellung
EP0004741B1 (de)	1981-01-28	Thioetiansäurederivate, ihre Herstellung und ihre pharmazeutische Anwendung
US4263289A (en)	1981-04-21	Thio etianic acid derivatives
US4187301A (en)	1980-02-05	17 Beta-thiocarboxylic acid esters of 6 alpha, 6 beta-difluoro-3-oxoandrost-4-enes
NO157020B (no)	1987-09-28	Analogifremgangsmte ved fremstilling av terapeutisk aktive 3,20-dioxo-1,4-pregnadien-17alfa-ol-17-aromatiske heterocykliske carboxylater.
CA1056371A (en)	1979-06-12	Polyhalogeno-steroids and processes for their manufacture
US4261984A (en)	1981-04-14	17β-thiocarboxylic acid esters of 3-oxo-4-halo-16β-methylandrost-4-enes
US4310466A (en)	1982-01-12	Thio etianic acid derivatives
US3989686A (en)	1976-11-02	Anaesthetic steroids of the androstane series and process for preparing same
DK142289B (da)	1980-10-06	Analogifremgangsmåde til fremstilling af D-homopregn-4-en-3,20-dioner.
CA1155108A (en)	1983-10-11	17.alpha.-ACYLOXY-5.beta. AND 5.alpha. CORTICOIDS
NO154268B (no)	1986-05-12	Analogifremgangsmùte ved fremstilling av nye terapeutisk a ktive 6a-fluor-9a-klor-prednisolon-17,21-diestere.
DK146017B (da)	1983-05-24	Analogifremgangsmaade til fremstilling af 17alfa-acyloxy-9alfa,21-dihalogen-11beta-hydroxy-6alfa-fluor-16beta-methyl-pregna-1,4-dien-3,20-dion-forbindelser
NO177147B (no)	1995-04-18	Analogifremgangsmåte for fremstilling av nye, terapeutisk aktive steroiddioler
GB2105724A (en)	1983-03-30	Corticoid 17-ester 21-thioesters
GB2089808A (en)	1982-06-30	5 alpha - and 5 beta -androstane-17 beta - carboxylates and -thiocarboxylates
NO791144L (no)	1979-10-08	4-halogenetansyre og derivater derav, samt fremgangsmaate til deres fremstilling
US4261986A (en)	1981-04-14	4-Halo etianic acids and derivatives thereof
NO791143L (no)	1979-10-08	4,6-dihalogensteroider, og fremgangsmaate til deres fremstilling
US3440252A (en)	1969-04-22	Preparation of 21-deoxy steroids
US4278669A (en)	1981-07-14	3-Oxo-4-halo-16β-methylandrost-4-ene 17β-carboxylic acids and esters
US3009932A (en)	1961-11-21	6-fluoro-9alpha, 11beta- 21-trihalo-progesterones
US3408369A (en)	1968-10-29	2-substituted-3-keto-delta4, 6-9beta, 10alpha-steroids
US3114750A (en)	1963-12-17	3-enol ethers of 6-formyl-3-oxo-delta4-steroids and process for their preparation
US3489748A (en)	1970-01-13	16alpha-thio-9beta,10alpha-delta**4-pregnene - 3 - ones and intermediates in the preparation thereof