CS203956B2 - Method of producing derivatives of 3-oxoandrostene /or androstadiene/ thiocarboxylic acid - Google Patents

Method of producing derivatives of 3-oxoandrostene /or androstadiene/ thiocarboxylic acid Download PDF

Info

Publication number: CS203956B2
Authority: CS; Czechoslovakia
Prior art keywords: methyl; acid; diene; hydrogen; chlorine
Prior art date: 1978-04-05

Application number

CS792107A

Other languages

Czech (cs)

English (en)

Inventor

John A Edwards

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

1979-03-29

Publication date

1981-03-31

1979-03-29 Application filed by Syntex Inc filed Critical Syntex Inc

1981-03-31 Publication of CS203956B2 publication Critical patent/CS203956B2/cs

Links

238000000034 method Methods 0.000 title claims description 30
NYGWTZLABYSHOP-FCYODTKKSA-N (8R,9S,10S,13R)-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12-decahydro-1H-cyclopenta[a]phenanthrene Chemical compound C([C@H]12)CC3CCCC[C@]3(C)[C@H]1CC[C@@]1(C)C2=CC=C1 NYGWTZLABYSHOP-FCYODTKKSA-N 0.000 title claims description 6
MSEZLHAVPJYYIQ-VMXHOPILSA-N (8s,9s,10r,13s,14s)-10,13-dimethyl-1,2,6,7,8,9,11,12,14,15,16,17-dodecahydrocyclopenta[a]phenanthren-3-one Chemical class C1CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CCC[C@@]1(C)CC2 MSEZLHAVPJYYIQ-VMXHOPILSA-N 0.000 title claims description 6
150000003566 thiocarboxylic acids Chemical class 0.000 title 1
229910052739 hydrogen Inorganic materials 0.000 claims abstract description 20
239000001257 hydrogen Substances 0.000 claims abstract description 19
125000001309 chloro group Chemical group Cl* 0.000 claims abstract description 16
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 14
125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 10
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims abstract description 9
125000001589 carboacyl group Chemical group 0.000 claims abstract description 5
239000007787 solid Substances 0.000 claims abstract description 5
150000001875 compounds Chemical class 0.000 claims description 41
229910052801 chlorine Inorganic materials 0.000 claims description 27
238000002360 preparation method Methods 0.000 claims description 24
239000000460 chlorine Substances 0.000 claims description 20
229910052731 fluorine Inorganic materials 0.000 claims description 19
239000011737 fluorine Substances 0.000 claims description 17
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 9
230000008569 process Effects 0.000 claims description 9
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 7
KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 claims description 6
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 6
150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 4
150000003565 thiocarboxylic acid derivatives Chemical class 0.000 claims description 3
150000001447 alkali salts Chemical class 0.000 claims description 2
125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 1
-1 Thio etianic acid derivatives Chemical class 0.000 abstract description 20
125000000217 alkyl group Chemical group 0.000 abstract description 19
150000003431 steroids Chemical class 0.000 abstract description 12
230000003110 anti-inflammatory effect Effects 0.000 abstract description 11
125000004432 carbon atom Chemical group C* 0.000 abstract description 8
229910052783 alkali metal Inorganic materials 0.000 abstract description 4
125000001153 fluoro group Chemical group F* 0.000 abstract description 4
125000001424 substituent group Chemical group 0.000 abstract description 3
125000003545 alkoxy group Chemical group 0.000 abstract description 2
125000001246 bromo group Chemical group Br* 0.000 abstract description 2
125000005843 halogen group Chemical group 0.000 abstract 1
239000000203 mixture Substances 0.000 description 25
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 21
239000002253 acid Substances 0.000 description 21
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 18
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 18
239000002904 solvent Substances 0.000 description 18
239000000243 solution Substances 0.000 description 16
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 12
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 12
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 12
LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 10
YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 description 10
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 10
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 10
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 9
DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 9
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
238000006243 chemical reaction Methods 0.000 description 9
230000000694 effects Effects 0.000 description 9
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 9
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 9
150000004702 methyl esters Chemical class 0.000 description 8
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 7
239000000546 pharmaceutical excipient Substances 0.000 description 7
239000011541 reaction mixture Substances 0.000 description 7
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 6
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
150000002431 hydrogen Chemical class 0.000 description 6
238000003756 stirring Methods 0.000 description 6
241001465754 Metazoa Species 0.000 description 5
239000004480 active ingredient Substances 0.000 description 5
239000002585 base Substances 0.000 description 5
LGTLXDJOAJDFLR-UHFFFAOYSA-N diethyl chlorophosphate Chemical compound CCOP(Cl)(=O)OCC LGTLXDJOAJDFLR-UHFFFAOYSA-N 0.000 description 5
238000009472 formulation Methods 0.000 description 5
229960000890 hydrocortisone Drugs 0.000 description 5
WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 5
RUOJZAUFBMNUDX-UHFFFAOYSA-N propylene carbonate Chemical compound CC1COC(=O)O1 RUOJZAUFBMNUDX-UHFFFAOYSA-N 0.000 description 5
239000007858 starting material Substances 0.000 description 5
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
QMMFVYPAHWMCMS-UHFFFAOYSA-N Dimethyl sulfide Chemical compound CSC QMMFVYPAHWMCMS-UHFFFAOYSA-N 0.000 description 4
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 4
241000124008 Mammalia Species 0.000 description 4
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
230000008901 benefit Effects 0.000 description 4
LUFPJJNWMYZRQE-UHFFFAOYSA-N benzylsulfanylmethylbenzene Chemical compound C=1C=CC=CC=1CSCC1=CC=CC=C1 LUFPJJNWMYZRQE-UHFFFAOYSA-N 0.000 description 4
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 4
229910052794 bromium Inorganic materials 0.000 description 4
229910052799 carbon Inorganic materials 0.000 description 4
239000006071 cream Substances 0.000 description 4
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 4
150000002191 fatty alcohols Chemical class 0.000 description 4
239000000706 filtrate Substances 0.000 description 4
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 4
125000002887 hydroxy group Chemical group [H]O* 0.000 description 4
238000004519 manufacturing process Methods 0.000 description 4
239000002480 mineral oil Substances 0.000 description 4
VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical compound OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 description 4
239000008194 pharmaceutical composition Substances 0.000 description 4
239000002244 precipitate Substances 0.000 description 4
230000001225 therapeutic effect Effects 0.000 description 4
230000000699 topical effect Effects 0.000 description 4
239000000080 wetting agent Substances 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
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
241000700159 Rattus Species 0.000 description 3
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 3
206010047139 Vasoconstriction Diseases 0.000 description 3
229960000583 acetic acid Drugs 0.000 description 3
WFDIJRYMOXRFFG-UHFFFAOYSA-N acetic acid anhydride Natural products CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
239000002671 adjuvant Substances 0.000 description 3
150000008064 anhydrides Chemical class 0.000 description 3
238000000354 decomposition reaction Methods 0.000 description 3
LJSQFQKUNVCTIA-UHFFFAOYSA-N diethyl sulfide Chemical compound CCSCC LJSQFQKUNVCTIA-UHFFFAOYSA-N 0.000 description 3
229960001347 fluocinolone acetonide Drugs 0.000 description 3
210000000245 forearm Anatomy 0.000 description 3
239000000463 material Substances 0.000 description 3
235000010446 mineral oil Nutrition 0.000 description 3
229910052757 nitrogen Inorganic materials 0.000 description 3
239000002674 ointment Substances 0.000 description 3
239000003883 ointment base Substances 0.000 description 3
239000000047 product Substances 0.000 description 3
229910000104 sodium hydride Inorganic materials 0.000 description 3
239000012312 sodium hydride Substances 0.000 description 3
239000003381 stabilizer Substances 0.000 description 3
210000001541 thymus gland Anatomy 0.000 description 3
230000025033 vasoconstriction Effects 0.000 description 3
239000003871 white petrolatum Substances 0.000 description 3
FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Chemical compound CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 2
ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-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
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
LCTONWCANYUPML-UHFFFAOYSA-N Pyruvic acid Chemical compound CC(=O)C(O)=O LCTONWCANYUPML-UHFFFAOYSA-N 0.000 description 2
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 2
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 2
125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 2
239000003377 acid catalyst Substances 0.000 description 2
150000007513 acids Chemical class 0.000 description 2
239000003963 antioxidant agent Substances 0.000 description 2
239000012298 atmosphere Substances 0.000 description 2
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
239000012267 brine Substances 0.000 description 2
239000003153 chemical reaction reagent Substances 0.000 description 2
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 2
XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
231100000673 dose–response relationship Toxicity 0.000 description 2
230000008030 elimination Effects 0.000 description 2
238000003379 elimination reaction Methods 0.000 description 2
239000000839 emulsion Substances 0.000 description 2
150000002148 esters Chemical class 0.000 description 2
125000004494 ethyl ester group Chemical group 0.000 description 2
239000012362 glacial acetic acid Substances 0.000 description 2
229910052736 halogen Inorganic materials 0.000 description 2
150000002367 halogens Chemical class 0.000 description 2
238000010438 heat treatment Methods 0.000 description 2
KDCIHNCMPUBDKT-UHFFFAOYSA-N hexane;propan-2-one Chemical compound CC(C)=O.CCCCCC KDCIHNCMPUBDKT-UHFFFAOYSA-N 0.000 description 2
229910000042 hydrogen bromide Inorganic materials 0.000 description 2
IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 2
229910000041 hydrogen chloride Inorganic materials 0.000 description 2
JGJLWPGRMCADHB-UHFFFAOYSA-N hypobromite Chemical compound Br[O-] JGJLWPGRMCADHB-UHFFFAOYSA-N 0.000 description 2
239000012442 inert solvent Substances 0.000 description 2
230000004968 inflammatory condition Effects 0.000 description 2
230000002757 inflammatory effect Effects 0.000 description 2
239000004615 ingredient Substances 0.000 description 2
235000019388 lanolin Nutrition 0.000 description 2
YSVZADAAWQNYCF-UHFFFAOYSA-N methylsulfanylmethane;sodium Chemical compound [Na].CSC YSVZADAAWQNYCF-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
239000012299 nitrogen atmosphere Substances 0.000 description 2
239000002736 nonionic surfactant Substances 0.000 description 2
239000003921 oil Substances 0.000 description 2
239000001301 oxygen Substances 0.000 description 2
229910052760 oxygen Inorganic materials 0.000 description 2
SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 description 2
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
YPFDHNVEDLHUCE-UHFFFAOYSA-N propane-1,3-diol Chemical compound OCCCO YPFDHNVEDLHUCE-UHFFFAOYSA-N 0.000 description 2
WYVAMUWZEOHJOQ-UHFFFAOYSA-N propionic anhydride Chemical compound CCC(=O)OC(=O)CC WYVAMUWZEOHJOQ-UHFFFAOYSA-N 0.000 description 2
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
238000010992 reflux Methods 0.000 description 2
150000003839 salts Chemical class 0.000 description 2
229910052938 sodium sulfate Inorganic materials 0.000 description 2
235000011152 sodium sulphate Nutrition 0.000 description 2
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 2
AKEJUJNQAAGONA-UHFFFAOYSA-N sulfur trioxide Chemical compound O=S(=O)=O AKEJUJNQAAGONA-UHFFFAOYSA-N 0.000 description 2
238000004809 thin layer chromatography Methods 0.000 description 2
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 2
SCOGDVKNVFYAOV-YGYHCWFDSA-N (8R,9S,10R,13S,14S)-15-benzyl-10,13-dimethyl-1,2,6,7,8,9,11,12,14,15,16,17-dodecahydrocyclopenta[a]phenanthren-3-one Chemical compound C(C1=CC=CC=C1)C1[C@@H]2[C@](CC1)(C)CC[C@H]1[C@H]2CCC2=CC(CC[C@]12C)=O SCOGDVKNVFYAOV-YGYHCWFDSA-N 0.000 description 1
OGVALIJQJSYXAT-YFWFAHHUSA-N (8S,9S,10R,13S,14S,17S)-17-(2-hydroxyacetyl)-10,13-dimethyl-1,3,6,7,8,9,11,12,14,15,16,17-dodecahydrocyclopenta[a]phenanthren-2-one Chemical compound C(C([C@H]1CC[C@H]2[C@@H]3CCC4=CCC(C[C@]4(C)[C@H]3CC[C@]12C)=O)=O)O OGVALIJQJSYXAT-YFWFAHHUSA-N 0.000 description 1
BFSFGTRRKLICIP-ARDGFHNTSA-N (8r,9s,10s,13s,14s)-17-ethyl-10,13,16-trimethyl-2,3,4,5,6,7,8,9,11,12,14,15-dodecahydro-1h-cyclopenta[a]phenanthrene Chemical compound C1CC2CCCC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC(C)=C(CC)[C@@]1(C)CC2 BFSFGTRRKLICIP-ARDGFHNTSA-N 0.000 description 1
CBYCRMIWATZBBW-RDQPJNLGSA-N (8r,9s,10s,13s,14s)-17-ethyl-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15-dodecahydro-1h-cyclopenta[a]phenanthrene Chemical compound C1CC2CCCC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC=C(CC)[C@@]1(C)CC2 CBYCRMIWATZBBW-RDQPJNLGSA-N 0.000 description 1
QQCBOIWDENXRLP-BYZMTCBYSA-N (8s,9s,10r,13r,14s,17s)-17-ethyl-10,13-dimethyl-6,7,8,9,11,12,14,15,16,17-decahydro-3h-cyclopenta[a]phenanthrene Chemical compound C1CC2=CCC=C[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H](CC)[C@@]1(C)CC2 QQCBOIWDENXRLP-BYZMTCBYSA-N 0.000 description 1
LOKKIZQIOKLFKB-USUWBSJTSA-N (8s,9s,10r,13r,14s,17s)-17-ethyl-3-methoxy-10,13-dimethyl-2,7,8,9,11,12,14,15,16,17-decahydro-1h-cyclopenta[a]phenanthrene Chemical compound C1C=C2C=C(OC)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H](CC)[C@@]1(C)CC2 LOKKIZQIOKLFKB-USUWBSJTSA-N 0.000 description 1
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 compound C1CC2=CCCC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CCC[C@@]1(C)CC2 IATKKATWPOVYCC-VMXHOPILSA-N 0.000 description 1
OKLGUHSWDMERAF-UDCWSGSHSA-N (8s,9s,10r,13s,14s,17s)-10,13-dimethyl-3-oxo-6,7,8,9,11,12,14,15,16,17-decahydrocyclopenta[a]phenanthrene-17-carbothioic s-acid Chemical compound O=C1C=C[C@]2(C)[C@H]3CC[C@](C)([C@H](CC4)C(O)=S)[C@@H]4[C@@H]3CCC2=C1 OKLGUHSWDMERAF-UDCWSGSHSA-N 0.000 description 1
ZQCAOHVYAHPGEW-UDCWSGSHSA-N (8s,9s,10r,13s,14s,17s)-10,13-dimethyl-6,7,8,9,11,12,14,15,16,17-decahydro-3h-cyclopenta[a]phenanthrene-17-carboxylic acid Chemical compound C1C=C[C@]2(C)[C@H]3CC[C@](C)([C@H](CC4)C(O)=O)[C@@H]4[C@@H]3CCC2=C1 ZQCAOHVYAHPGEW-UDCWSGSHSA-N 0.000 description 1
ZWVMLYRJXORSEP-UHFFFAOYSA-N 1,2,6-Hexanetriol Chemical compound OCCCCC(O)CO ZWVMLYRJXORSEP-UHFFFAOYSA-N 0.000 description 1
NWUYHJFMYQTDRP-UHFFFAOYSA-N 1,2-bis(ethenyl)benzene;1-ethenyl-2-ethylbenzene;styrene Chemical compound C=CC1=CC=CC=C1.CCC1=CC=CC=C1C=C.C=CC1=CC=CC=C1C=C NWUYHJFMYQTDRP-UHFFFAOYSA-N 0.000 description 1
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
DBPWSSGDRRHUNT-UHFFFAOYSA-N 17alpha-hydroxy progesterone Natural products C1CC2=CC(=O)CCC2(C)C2C1C1CCC(C(=O)C)(O)C1(C)CC2 DBPWSSGDRRHUNT-UHFFFAOYSA-N 0.000 description 1
YNBXFUVMYLCPCS-YFWFAHHUSA-N 2-[(8S,9S,10R,13S,14S,17S)-10,13-dimethyl-2,3,6,7,8,9,11,12,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-17-yl]-2-oxoacetaldehyde Chemical class O=C(C=O)[C@H]1CC[C@H]2[C@@H]3CCC4=CCCC[C@]4(C)[C@H]3CC[C@]12C YNBXFUVMYLCPCS-YFWFAHHUSA-N 0.000 description 1
NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 1
WXHLLJAMBQLULT-UHFFFAOYSA-N 2-[[6-[4-(2-hydroxyethyl)piperazin-1-yl]-2-methylpyrimidin-4-yl]amino]-n-(2-methyl-6-sulfanylphenyl)-1,3-thiazole-5-carboxamide;hydrate Chemical compound O.C=1C(N2CCN(CCO)CC2)=NC(C)=NC=1NC(S1)=NC=C1C(=O)NC1=C(C)C=CC=C1S WXHLLJAMBQLULT-UHFFFAOYSA-N 0.000 description 1
GLVYLTSKTCWWJR-UHFFFAOYSA-N 2-carbonoperoxoylbenzoic acid Chemical compound OOC(=O)C1=CC=CC=C1C(O)=O GLVYLTSKTCWWJR-UHFFFAOYSA-N 0.000 description 1
241000903210 Bryconamericus alpha Species 0.000 description 1
GAWIXWVDTYZWAW-UHFFFAOYSA-N C[CH]O Chemical group C[CH]O GAWIXWVDTYZWAW-UHFFFAOYSA-N 0.000 description 1
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
229940126062 Compound A Drugs 0.000 description 1
229910021591 Copper(I) chloride Inorganic materials 0.000 description 1
OMFXVFTZEKFJBZ-UHFFFAOYSA-N Corticosterone Natural products O=C1CCC2(C)C3C(O)CC(C)(C(CC4)C(=O)CO)C4C3CCC2=C1 OMFXVFTZEKFJBZ-UHFFFAOYSA-N 0.000 description 1
YXHKONLOYHBTNS-UHFFFAOYSA-N Diazomethane Chemical compound C=[N+]=[N-] YXHKONLOYHBTNS-UHFFFAOYSA-N 0.000 description 1
HTIRHQRTDBPHNZ-UHFFFAOYSA-N Dibutyl sulfide Chemical compound CCCCSCCCC HTIRHQRTDBPHNZ-UHFFFAOYSA-N 0.000 description 1
KRHYYFGTRYWZRS-UHFFFAOYSA-N Fluorane Chemical compound F KRHYYFGTRYWZRS-UHFFFAOYSA-N 0.000 description 1
KRHYYFGTRYWZRS-UHFFFAOYSA-M Fluoride anion Chemical compound [F-] KRHYYFGTRYWZRS-UHFFFAOYSA-M 0.000 description 1
NLDMNSXOCDLTTB-UHFFFAOYSA-N Heterophylliin A Natural products O1C2COC(=O)C3=CC(O)=C(O)C(O)=C3C3=C(O)C(O)=C(O)C=C3C(=O)OC2C(OC(=O)C=2C=C(O)C(O)=C(O)C=2)C(O)C1OC(=O)C1=CC(O)=C(O)C(O)=C1 NLDMNSXOCDLTTB-UHFFFAOYSA-N 0.000 description 1
DOMWKUIIPQCAJU-LJHIYBGHSA-N Hydroxyprogesterone caproate Chemical compound C1CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@@](C(C)=O)(OC(=O)CCCCC)[C@@]1(C)CC2 DOMWKUIIPQCAJU-LJHIYBGHSA-N 0.000 description 1
229930194542 Keto Natural products 0.000 description 1
239000004166 Lanolin Substances 0.000 description 1
239000012359 Methanesulfonyl chloride Substances 0.000 description 1
241000699670 Mus sp. Species 0.000 description 1
FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 1
SUAKHGWARZSWIH-UHFFFAOYSA-N N,N‐diethylformamide Chemical compound CCN(CC)C=O SUAKHGWARZSWIH-UHFFFAOYSA-N 0.000 description 1
229910019142 PO4 Inorganic materials 0.000 description 1
MKPDWECBUAZOHP-AFYJWTTESA-N Paramethasone 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)CO)(O)[C@@]2(C)C[C@@H]1O MKPDWECBUAZOHP-AFYJWTTESA-N 0.000 description 1
241000555028 Sternidius alpha Species 0.000 description 1
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
238000010521 absorption reaction Methods 0.000 description 1
DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 1
WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 1
239000012346 acetyl chloride Substances 0.000 description 1
150000008065 acid anhydrides Chemical class 0.000 description 1
230000009471 action Effects 0.000 description 1
239000013543 active substance Substances 0.000 description 1
230000002411 adverse Effects 0.000 description 1
238000007605 air drying Methods 0.000 description 1
230000001476 alcoholic effect Effects 0.000 description 1
229910000288 alkali metal carbonate Inorganic materials 0.000 description 1
150000008041 alkali metal carbonates Chemical class 0.000 description 1
229910000102 alkali metal hydride Inorganic materials 0.000 description 1
150000008046 alkali metal hydrides Chemical class 0.000 description 1
150000001340 alkali metals Chemical class 0.000 description 1
QZLYKIGBANMMBK-UGCZWRCOSA-N androstane group Chemical group [C@@H]12CCC[C@@]1(C)CC[C@H]1[C@H]2CC[C@H]2CCCC[C@]12C QZLYKIGBANMMBK-UGCZWRCOSA-N 0.000 description 1
229940035674 anesthetics Drugs 0.000 description 1
229960004543 anhydrous citric acid Drugs 0.000 description 1
230000002421 anti-septic effect Effects 0.000 description 1
229940064004 antiseptic throat preparations Drugs 0.000 description 1
238000003556 assay Methods 0.000 description 1
125000004429 atom Chemical group 0.000 description 1
WAIDETQZCMAFQJ-UHFFFAOYSA-N benzylsulfanylmethylbenzene;sodium Chemical compound [Na].C=1C=CC=CC=1CSCC1=CC=CC=C1 WAIDETQZCMAFQJ-UHFFFAOYSA-N 0.000 description 1
UREBDLICKHMUKA-DVTGEIKXSA-N betamethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O UREBDLICKHMUKA-DVTGEIKXSA-N 0.000 description 1
239000011230 binding agent Substances 0.000 description 1
230000004071 biological effect Effects 0.000 description 1
238000009835 boiling Methods 0.000 description 1
230000005587 bubbling Effects 0.000 description 1
125000004063 butyryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
239000004202 carbamide Substances 0.000 description 1
PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 1
239000001768 carboxy methyl cellulose Substances 0.000 description 1
150000001735 carboxylic acids Chemical class 0.000 description 1
239000003054 catalyst Substances 0.000 description 1
230000003197 catalytic effect Effects 0.000 description 1
239000003729 cation exchange resin Substances 0.000 description 1
150000001805 chlorine compounds Chemical class 0.000 description 1
ITVPBBDAZKBMRP-UHFFFAOYSA-N chloro-dioxido-oxo-$l^{5}-phosphane;hydron Chemical compound OP(O)(Cl)=O ITVPBBDAZKBMRP-UHFFFAOYSA-N 0.000 description 1
238000004587 chromatography analysis Methods 0.000 description 1
229940117975 chromium trioxide Drugs 0.000 description 1
WGLPBDUCMAPZCE-UHFFFAOYSA-N chromium trioxide Inorganic materials O=[Cr](=O)=O WGLPBDUCMAPZCE-UHFFFAOYSA-N 0.000 description 1
GAMDZJFZMJECOS-UHFFFAOYSA-N chromium(6+);oxygen(2-) Chemical compound [O-2].[O-2].[O-2].[Cr+6] GAMDZJFZMJECOS-UHFFFAOYSA-N 0.000 description 1
GPNHMOZDMYNCPO-PDUMRIMRSA-N clascoterone Chemical compound C1CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@@](C(=O)CO)(OC(=O)CC)[C@@]1(C)CC2 GPNHMOZDMYNCPO-PDUMRIMRSA-N 0.000 description 1
230000000052 comparative effect Effects 0.000 description 1
OXBLHERUFWYNTN-UHFFFAOYSA-M copper(I) chloride Chemical compound [Cu]Cl OXBLHERUFWYNTN-UHFFFAOYSA-M 0.000 description 1
OMFXVFTZEKFJBZ-HJTSIMOOSA-N corticosterone Chemical compound O=C1CC[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@H](CC4)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 OMFXVFTZEKFJBZ-HJTSIMOOSA-N 0.000 description 1
239000002178 crystalline material Substances 0.000 description 1
238000007405 data analysis Methods 0.000 description 1
229960003957 dexamethasone Drugs 0.000 description 1
UREBDLICKHMUKA-CXSFZGCWSA-N dexamethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O UREBDLICKHMUKA-CXSFZGCWSA-N 0.000 description 1
125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 description 1
LTYMSROWYAPPGB-UHFFFAOYSA-N diphenyl sulfide Chemical compound C=1C=CC=CC=1SC1=CC=CC=C1 LTYMSROWYAPPGB-UHFFFAOYSA-N 0.000 description 1
SZXQTJUDPRGNJN-UHFFFAOYSA-N dipropylene glycol Chemical compound OCCCOCCCO SZXQTJUDPRGNJN-UHFFFAOYSA-N 0.000 description 1
230000008034 disappearance Effects 0.000 description 1
239000002552 dosage form Substances 0.000 description 1
GKIPXFAANLTWBM-UHFFFAOYSA-N epibromohydrin Chemical compound BrCC1CO1 GKIPXFAANLTWBM-UHFFFAOYSA-N 0.000 description 1
230000032050 esterification Effects 0.000 description 1
238000005886 esterification reaction Methods 0.000 description 1
239000003925 fat Substances 0.000 description 1
229960003469 flumetasone Drugs 0.000 description 1
WXURHACBFYSXBI-GQKYHHCASA-N flumethasone 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](C)[C@@](C(=O)CO)(O)[C@@]2(C)C[C@@H]1O WXURHACBFYSXBI-GQKYHHCASA-N 0.000 description 1
229940043075 fluocinolone Drugs 0.000 description 1
239000006260 foam Substances 0.000 description 1
WBJINCZRORDGAQ-UHFFFAOYSA-N formic acid ethyl ester Natural products CCOC=O WBJINCZRORDGAQ-UHFFFAOYSA-N 0.000 description 1
239000000499 gel Substances 0.000 description 1
239000003193 general anesthetic agent Substances 0.000 description 1
235000011187 glycerol Nutrition 0.000 description 1
229910000040 hydrogen fluoride Inorganic materials 0.000 description 1
229950000801 hydroxyprogesterone caproate Drugs 0.000 description 1
238000011065 in-situ storage Methods 0.000 description 1
238000002347 injection Methods 0.000 description 1
239000007924 injection Substances 0.000 description 1
125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
238000002955 isolation Methods 0.000 description 1
125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
125000000468 ketone group Chemical group 0.000 description 1
238000009533 lab test Methods 0.000 description 1
229940039717 lanolin Drugs 0.000 description 1
239000007788 liquid Substances 0.000 description 1
239000006210 lotion Substances 0.000 description 1
239000000314 lubricant Substances 0.000 description 1
NXPHGHWWQRMDIA-UHFFFAOYSA-M magnesium;carbanide;bromide Chemical compound [CH3-].[Mg+2].[Br-] NXPHGHWWQRMDIA-UHFFFAOYSA-M 0.000 description 1
238000003760 magnetic stirring Methods 0.000 description 1
QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 1
UKEKSQXYJALFKZ-UHFFFAOYSA-N methylsulfanylmethane;potassium Chemical compound [K].CSC UKEKSQXYJALFKZ-UHFFFAOYSA-N 0.000 description 1
238000002156 mixing Methods 0.000 description 1
230000004048 modification Effects 0.000 description 1
238000012986 modification Methods 0.000 description 1
125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 description 1
VBTQNRFWXBXZQR-UHFFFAOYSA-N n-bromoacetamide Chemical compound CC(=O)NBr VBTQNRFWXBXZQR-UHFFFAOYSA-N 0.000 description 1
125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 1
125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
231100000344 non-irritating Toxicity 0.000 description 1
231100000252 nontoxic Toxicity 0.000 description 1
230000003000 nontoxic effect Effects 0.000 description 1
230000003647 oxidation Effects 0.000 description 1
238000007254 oxidation reaction Methods 0.000 description 1
230000001590 oxidative effect Effects 0.000 description 1
150000002926 oxygen Chemical class 0.000 description 1
229910052763 palladium Inorganic materials 0.000 description 1
229960002858 paramethasone Drugs 0.000 description 1
125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
KHIWWQKSHDUIBK-UHFFFAOYSA-N periodic acid Chemical compound OI(=O)(=O)=O KHIWWQKSHDUIBK-UHFFFAOYSA-N 0.000 description 1
235000019271 petrolatum Nutrition 0.000 description 1
239000003208 petroleum Substances 0.000 description 1
229940124531 pharmaceutical excipient Drugs 0.000 description 1
NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
239000010452 phosphate Substances 0.000 description 1
239000004014 plasticizer Substances 0.000 description 1
238000007747 plating Methods 0.000 description 1
229940093429 polyethylene glycol 6000 Drugs 0.000 description 1
229920000136 polysorbate Polymers 0.000 description 1
235000011056 potassium acetate Nutrition 0.000 description 1
229910000027 potassium carbonate Inorganic materials 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
229960005205 prednisolone Drugs 0.000 description 1
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 1
AYGFEWYXKDFVIQ-NWSAAYAGSA-N pregn-4-en-3-one Chemical compound C1CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H](CC)[C@@]1(C)CC2 AYGFEWYXKDFVIQ-NWSAAYAGSA-N 0.000 description 1
OVARTBFNCCXQKS-UHFFFAOYSA-N propan-2-one;hydrate Chemical compound O.CC(C)=O OVARTBFNCCXQKS-UHFFFAOYSA-N 0.000 description 1
235000019260 propionic acid Nutrition 0.000 description 1
125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
LVTJOONKWUXEFR-FZRMHRINSA-N protoneodioscin Natural products O(C[C@@H](CC[C@]1(O)[C@H](C)[C@@H]2[C@]3(C)[C@H]([C@H]4[C@@H]([C@]5(C)C(=CC4)C[C@@H](O[C@@H]4[C@H](O[C@H]6[C@@H](O)[C@@H](O)[C@@H](O)[C@H](C)O6)[C@@H](O)[C@H](O[C@H]6[C@@H](O)[C@@H](O)[C@@H](O)[C@H](C)O6)[C@H](CO)O4)CC5)CC3)C[C@@H]2O1)C)[C@H]1[C@H](O)[C@H](O)[C@H](O)[C@@H](CO)O1 LVTJOONKWUXEFR-FZRMHRINSA-N 0.000 description 1
229940107700 pyruvic acid Drugs 0.000 description 1
IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
238000001953 recrystallisation Methods 0.000 description 1
238000010898 silica gel chromatography Methods 0.000 description 1
208000017520 skin disease Diseases 0.000 description 1
235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
RZWQDAUIUBVCDD-UHFFFAOYSA-M sodium;benzenethiolate Chemical compound [Na+].[S-]C1=CC=CC=C1 RZWQDAUIUBVCDD-UHFFFAOYSA-M 0.000 description 1
241000894007 species Species 0.000 description 1
238000010254 subcutaneous injection Methods 0.000 description 1
239000007929 subcutaneous injection Substances 0.000 description 1
239000000126 substance Substances 0.000 description 1
229910052717 sulfur Inorganic materials 0.000 description 1
239000011593 sulfur Substances 0.000 description 1
239000000829 suppository Substances 0.000 description 1
239000004094 surface-active agent Substances 0.000 description 1
239000000725 suspension Substances 0.000 description 1
230000009885 systemic effect Effects 0.000 description 1
125000000858 thiocyanato group Chemical group *SC#N 0.000 description 1
150000003568 thioethers Chemical class 0.000 description 1
125000005505 thiomorpholino group Chemical group 0.000 description 1
229940100611 topical cream Drugs 0.000 description 1
229960005294 triamcinolone Drugs 0.000 description 1
GFNANZIMVAIWHM-OBYCQNJPSA-N triamcinolone Chemical compound O=C1C=C[C@]2(C)[C@@]3(F)[C@@H](O)C[C@](C)([C@@]([C@H](O)C4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 GFNANZIMVAIWHM-OBYCQNJPSA-N 0.000 description 1
GKASDNZWUGIAMG-UHFFFAOYSA-N triethyl orthoformate Chemical compound CCOC(OCC)OCC GKASDNZWUGIAMG-UHFFFAOYSA-N 0.000 description 1
229960005486 vaccine Drugs 0.000 description 1
125000003774 valeryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
229940099259 vaseline Drugs 0.000 description 1
230000000007 visual effect Effects 0.000 description 1
238000005406 washing Methods 0.000 description 1
238000005303 weighing Methods 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
- C07J31/006—Normal steroids containing one or more sulfur atoms not belonging to a hetero ring not covered by C07J31/003
- 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]
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/38—Drugs for disorders of the endocrine system of the suprarenal hormones
- 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
- 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

Organic Chemistry (AREA)
Chemical & Material Sciences (AREA)
Health & Medical Sciences (AREA)
General Health & Medical Sciences (AREA)
Veterinary Medicine (AREA)
Animal Behavior & Ethology (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Life Sciences & Earth Sciences (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Pharmacology & Pharmacy (AREA)
Public Health (AREA)
Medicinal Chemistry (AREA)
Endocrinology (AREA)
Diabetes (AREA)
Bioinformatics & Cheminformatics (AREA)
Engineering & Computer Science (AREA)
Pain & Pain Management (AREA)
Rheumatology (AREA)
Steroid Compounds (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

CS792107A 1978-04-05 1979-03-29 Method of producing derivatives of 3-oxoandrostene /or androstadiene/ thiocarboxylic acid CS203956B2 (en)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
US05/893,388 US4188385A (en)	1978-04-05	1978-04-05	Thioetianic acid derivatives

Publications (1)

Publication Number	Publication Date
CS203956B2 true CS203956B2 (en)	1981-03-31

Family

ID=25401484

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
CS792107A CS203956B2 (en)	1978-04-05	1979-03-29	Method of producing derivatives of 3-oxoandrostene /or androstadiene/ thiocarboxylic acid

Country Status (28)

Country	Link
US (1)	US4188385A (da)
EP (1)	EP0004741B1 (da)
JP (2)	JPS54141758A (da)
AR (1)	AR226035A1 (da)
AT (1)	AT368168B (da)
AU (1)	AU526025B2 (da)
CA (1)	CA1134345A (da)
CS (1)	CS203956B2 (da)
DE (2)	DE2960096D1 (da)
DK (1)	DK147735C (da)
ES (1)	ES479271A1 (da)
FI (1)	FI66393C (da)
FR (1)	FR2421912A1 (da)
GB (1)	GB2018256B (da)
GR (1)	GR67275B (da)
HK (1)	HK41284A (da)
HU (1)	HU179314B (da)
IL (1)	IL56972A0 (da)
IT (1)	IT1120954B (da)
MY (1)	MY8500575A (da)
NO (1)	NO152935C (da)
NZ (1)	NZ190076A (da)
PL (1)	PL121469B1 (da)
PT (1)	PT69409A (da)
SG (1)	SG6786G (da)
SU (1)	SU1052161A3 (da)
YU (1)	YU40929B (da)
ZA (1)	ZA791635B (da)

Families Citing this family (37)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US4263289A (en) *	1978-04-05	1981-04-21	Syntex (U.S.A.) Inc.	Thio etianic acid derivatives
US4261984A (en) *	1978-04-05	1981-04-14	Syntex (U.S.A.) Inc.	17β-thiocarboxylic acid esters of 3-oxo-4-halo-16β-methylandrost-4-enes
US4310466A (en) *	1979-08-31	1982-01-12	Syntex (U.S.A.) Inc.	Thio etianic acid derivatives
IT1170717B (it) *	1980-02-15	1987-06-03	Glaxo Group Ltd	Carbotioati androstanici procedimento per prepararli e composizioni farmaceutiche che li contengono
GB2137206B (en) *	1980-02-15	1985-04-03	Glaxo Group Ltd	Androstane 17-carbothioc acid derivatives
PH24267A (en) *	1980-02-15	1990-05-29	Glaxo Group Ltd	Androstane carbothioates and pharmaceutical compositions containing the same
US4578221A (en) *	1980-04-23	1986-03-25	Glaxo Group Limited	Androstane carbothioic acids
SE449106B (sv) *	1980-07-10	1987-04-06	Otsuka Pharma Co Ltd	Steroid med anti-inflammatorisk verkan samt komposition innehallande denna
IL78144A0 (en) *	1985-04-04	1986-07-31	Draco Ab	Novel androstane-17beta-carboxylic acid esters
GB9225923D0 (en) *	1992-12-11	1993-02-03	Rhone Poulenc Rorer Ltd	New compositions of matter
CA2149777C (en) *	1992-12-24	2004-05-25	Michael John Ashton	New steroids
KR19990076859A (ko)	1995-12-29	1999-10-25	그레이엄 브레레톤, 레슬리 에드워즈	17.베타.-카르복시, 카르보티오 및 아미드 안드로스탄 유도체의락톤 유도체
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
GB0017988D0 (en) *	2000-07-21	2000-09-13	Glaxo Group Ltd	Novel process
US6750210B2 (en) *	2000-08-05	2004-06-15	Smithkline Beecham Corporation	Formulation containing novel anti-inflammatory androstane derivative
US6759398B2 (en)	2000-08-05	2004-07-06	Smithkline Beecham Corporation	Anti-inflammatory androstane derivative
US6787532B2 (en) *	2000-08-05	2004-09-07	Smithkline Beecham Corporation	Formulation containing anti-inflammatory androstane derivatives
EA005992B1 (ru) *	2000-08-05	2005-08-25	Глаксо Груп Лимитед	S-ФТОРМЕТИЛОВЫЙ ЭФИР 6α,9α-ДИФТОР-17α-[(2-ФУРАНИЛКАРБОНИЛ)ОКСИ]-11β-ГИДРОКСИ-16α-МЕТИЛ-3-ОКСОАНДРОСТА-1,4-ДИЕН-17β-КАРБОТИОКИСЛОТЫ В КАЧЕСТВЕ ПРОТИВОВОСПАЛИТЕЛЬНОГО АГЕНТА
GB0019172D0 (en) *	2000-08-05	2000-09-27	Glaxo Group Ltd	Novel compounds
US6858593B2 (en) *	2000-08-05	2005-02-22	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
US6777399B2 (en) *	2000-08-05	2004-08-17	Smithkline Beecham Corporation	Anti-inflammatory androstane derivative compositions
US6777400B2 (en) *	2000-08-05	2004-08-17	Smithkline Beecham Corporation	Anti-inflammatory androstane derivative compositions
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
CN1302007C (zh) *	2001-04-30	2007-02-28	葛兰素集团有限公司	具有抗炎性的在17.α位上具有环酯基的雄甾烷的17.β.－硫代羧酸酯衍生物
EP1395604B1 (en) *	2001-06-12	2008-06-25	Glaxo Group Limited	Novel anti inflammatory 17.alpha.-heterocyclic-esters of 17.beta.-carbothioate androstane derivatives
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
IL150654A (en)	2002-07-09	2006-12-10	Ori Lerman	Method for acid isolation 6α, 9α - difluoro - ß, 17α11 - dihydroxy - 16α - methylfargana - 3 - oxo - 1, 4 - diene - 17ß - carboxylate
WO2004087731A1 (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
TWI374147B (en) *	2006-01-27	2012-10-11	Sun Pharma Advance Res Company Ltd	Novel 11β-hydroxyandrosta-4-ene-3-ones
GB0615108D0 (en) *	2006-07-28	2006-09-06	Glaxo Group Ltd	Novel formulations
MX2010007023A (es) *	2007-12-21	2010-09-30	Schering Corp	Agonistas del receptor glucocorticoide sustituido de c20-c21.
WO2010147947A2 (en)	2009-06-16	2010-12-23	Schering Corporation	NOVEL [3,2-c] HETEROARYL STEROIDS AS GLUCOCORTICOID RECEPTOR AGONISTS, COMPOSITIONS AND USES THEREOF

Family Cites Families (5)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US2509171A (en) *	1946-02-06	1950-05-23	Ciba Ltd	Primary alcohols from thiocarboxylic acids and esters
US3636010A (en) *	1968-12-23	1972-01-18	Ciba Geigy Corp	Esters of steroid-17-carboxylic acids
US3989686A (en) *	1972-06-15	1976-11-02	Glaxo Laboratories Limited	Anaesthetic steroids of the androstane series and process for preparing same
GB1438940A (en) *	1972-07-19	1976-06-09	Glaxo Lab Ltd	17beta-haloalkoxycarbonyl-17alpha-oxysteroids
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 US05/893,388 patent/US4188385A/en not_active Expired - Lifetime
1979
- 1979-03-28 DE DE7979300500T patent/DE2960096D1/de not_active Expired
- 1979-03-28 FR FR7907823A patent/FR2421912A1/fr active Granted
- 1979-03-28 EP EP79300500A patent/EP0004741B1/en not_active Expired
- 1979-03-28 GB GB7910862A patent/GB2018256B/en not_active Expired
- 1979-03-28 IT IT67652/79A patent/IT1120954B/it active
- 1979-03-28 DE DE19792912331 patent/DE2912331A1/de not_active Ceased
- 1979-03-29 IL IL56972A patent/IL56972A0/xx not_active IP Right Cessation
- 1979-03-29 AU AU45583/79A patent/AU526025B2/en not_active Ceased
- 1979-03-29 CS CS792107A patent/CS203956B2/cs unknown
- 1979-03-30 AR AR276014A patent/AR226035A1/es active
- 1979-03-30 CA CA000324557A patent/CA1134345A/en not_active Expired
- 1979-03-30 PT PT69409A patent/PT69409A/pt unknown
- 1979-03-31 GR GR58748A patent/GR67275B/el unknown
- 1979-04-02 FI FI791081A patent/FI66393C/fi not_active IP Right Cessation
- 1979-04-02 NZ NZ190076A patent/NZ190076A/en unknown
- 1979-04-03 HU HU79SI1682A patent/HU179314B/hu not_active IP Right Cessation
- 1979-04-03 DK DK136579A patent/DK147735C/da not_active IP Right Cessation
- 1979-04-04 ES ES479271A patent/ES479271A1/es not_active Expired
- 1979-04-04 YU YU803/79A patent/YU40929B/xx unknown
- 1979-04-04 NO NO791140A patent/NO152935C/no unknown
- 1979-04-04 AT AT0251979A patent/AT368168B/de not_active IP Right Cessation
- 1979-04-04 SU SU792787402A patent/SU1052161A3/ru active
- 1979-04-04 PL PL1979214676A patent/PL121469B1/pl unknown
- 1979-04-05 ZA ZA791635A patent/ZA791635B/xx unknown
- 1979-04-05 JP JP4041479A patent/JPS54141758A/ja active Granted
1984
- 1984-05-10 HK HK412/80A patent/HK41284A/xx unknown
- 1984-07-27 JP JP59155726A patent/JPS6069019A/ja active Granted
1985
- 1985-12-30 MY MY575/85A patent/MY8500575A/xx unknown
1986
- 1986-01-22 SG SG67/86A patent/SG6786G/en unknown

Also Published As

Publication number	Publication date
GB2018256B (en)	1983-02-02
IT7967652A0 (it)	1979-03-28
DK136579A (da)	1979-10-06
CA1134345A (en)	1982-10-26
PL121469B1 (en)	1982-05-31
FI66393C (fi)	1984-10-10
GR67275B (da)	1981-06-26
EP0004741A3 (en)	1979-11-14
JPS6140648B2 (da)	1986-09-10
PL214676A1 (da)	1980-01-02
NO152935B (no)	1985-09-09
EP0004741A2 (en)	1979-10-17
AU526025B2 (en)	1982-12-16
FI66393B (fi)	1984-06-29
PT69409A (en)	1979-04-01
US4188385A (en)	1980-02-12
ATA251979A (de)	1982-01-15
FR2421912B1 (da)	1981-03-20
GB2018256A (en)	1979-10-17
NO152935C (no)	1985-12-18
AT368168B (de)	1982-09-27
JPS54141758A (en)	1979-11-05
IL56972A0 (en)	1979-05-31
DE2960096D1 (en)	1981-03-19
YU80379A (en)	1983-04-30
HU179314B (en)	1982-09-28
ES479271A1 (es)	1980-01-16
IT1120954B (it)	1986-03-26
MY8500575A (en)	1985-12-31
FI791081A (fi)	1979-10-06
AU4558379A (en)	1979-10-18
DK147735B (da)	1984-11-26
NO791140L (no)	1979-10-08
JPS611038B2 (da)	1986-01-13
DE2912331A1 (de)	1979-10-18
DK147735C (da)	1985-08-19
EP0004741B1 (en)	1981-01-28
JPS6069019A (ja)	1985-04-19
SU1052161A3 (ru)	1983-10-30
FR2421912A1 (fr)	1979-11-02
AR226035A1 (es)	1982-05-31
HK41284A (en)	1984-05-18
SG6786G (en)	1986-08-01
NZ190076A (en)	1984-07-31
YU40929B (en)	1986-08-31
ZA791635B (en)	1980-11-26

Publication	Publication Date	Title
CS203956B2 (en)	1981-03-31	Method of producing derivatives of 3-oxoandrostene /or androstadiene/ thiocarboxylic acid
EP0004773B1 (en)	1981-04-29	17-beta-thiocarboxylic acid esters of 4-halo-3-oxoandrost-4-enes, their pharmaceutical use and processes for their preparation
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
US4310466A (en)	1982-01-12	Thio etianic acid derivatives
US4076708A (en)	1978-02-28	Process for the preparation of 7α-halogeno-3-oxo-4-dehydro steroids and novel 7α-halogeno derivatives produced thereby
FI80888C (fi)	1990-08-10	Foerfarande foer framstaellning av terapeutiskt verkande steroida karboxylsyraestrar.
JPS6139959B2 (da)	1986-09-06
BG60799B2 (bg)	1996-03-29	Ароматни хетероциклени стероидни естери,получаването им и фармацевтични състави,които ги съдържат
US4261984A (en)	1981-04-14	17β-thiocarboxylic acid esters of 3-oxo-4-halo-16β-methylandrost-4-enes
US4226862A (en)	1980-10-07	Steroids and process for preparing the same
EP0029151B1 (en)	1985-09-25	6-alpha-fluoro-9-alpha-chloro-prednisolone-17,21 diesters, pharmaceutical compositions containing them and intermediates
US4024131A (en)	1977-05-17	16-Methyl-9α-halo steroid esters, ethers and preparation thereof
EP0004765B1 (en)	1981-12-30	Corticosteroid anti-inflammatory agents, their use and methods for their preparation
JPS6214557B2 (da)	1987-04-02
US4261986A (en)	1981-04-14	4-Halo etianic acids and derivatives thereof
US4278669A (en)	1981-07-14	3-Oxo-4-halo-16β-methylandrost-4-ene 17β-carboxylic acids and esters
CA1073449A (en)	1980-03-11	21-acetals and mixed acetals of steroidal 21-aldehydes, intermediates and methods of preparation
CS208494B2 (en)	1981-09-15	Method of making the alcylesters of the 4-halogen-3-oxoandrosta-1,4-dien-17 beta-cyrboxyl acid
US4273770A (en)	1981-06-16	4-Halo steroids
EP0095749B1 (en)	1986-09-17	17-spiroandrostenes
US4185101A (en)	1980-01-22	1,3,5(10),6,8-19-Nor-pregnapentaenes, their use as anti-psoriatic agents, and pharmaceutical formulations useful therefor
KR830000083B1 (ko)	1983-02-08	티오 에티안산 유도체의 제조 방법
IE48369B1 (en)	1984-12-26	Thio etanic acid derivatives,their preparation and pharmaceutical use
CS209915B2 (en)	1981-12-31	Method of making the 4-halogenpregna-1,4-dien-3,20-dions