CA1129407A - Antiinflammatory steroid of the androstane series - Google Patents

Antiinflammatory steroid of the androstane series

Info

Publication number: CA1129407A
Authority: CA; Canada
Prior art keywords: beta; alpha; methyl; fluoro; diene
Prior art date: 1978-02-08
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.): Expired

Application number

CA321,032A

Other languages

English (en)

French (fr)

Inventor

Gordon H. Phillipps

Edward A. Woollett

Brian M. Bain

Alan F. English

Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)

Glaxo Group Ltd

Original Assignee

Glaxo Group Ltd

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.)

1978-02-08

Filing date

1979-02-07

Publication date

1982-08-10

1979-02-07 Application filed by Glaxo Group Ltd filed Critical Glaxo Group Ltd

1982-08-10 Application granted granted Critical

1982-08-10 Publication of CA1129407A publication Critical patent/CA1129407A/en

Status Expired legal-status Critical Current

Links

150000001441 androstanes Chemical class 0.000 title description 2
239000002260 anti-inflammatory agent Substances 0.000 title description 2
150000001875 compounds Chemical class 0.000 claims description 25
-1 iodomethyl Chemical group 0.000 claims description 25
238000002360 preparation method Methods 0.000 claims description 21
WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 claims description 15
238000006243 chemical reaction Methods 0.000 claims description 13
238000000034 method Methods 0.000 claims description 13
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 12
125000004218 chloromethyl group Chemical group [H]C([H])(Cl)* 0.000 claims description 11
125000005997 bromomethyl group Chemical group 0.000 claims description 7
150000008064 anhydrides Chemical class 0.000 claims description 6
229910052801 chlorine Inorganic materials 0.000 claims description 5
150000003839 salts Chemical class 0.000 claims description 5
239000000460 chlorine Substances 0.000 claims description 4
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 claims description 3
229910052783 alkali metal Inorganic materials 0.000 claims description 3
150000001340 alkali metals Chemical class 0.000 claims description 3
229910052731 fluorine Inorganic materials 0.000 claims description 3
229910052736 halogen Inorganic materials 0.000 claims description 3
125000005843 halogen group Chemical group 0.000 claims description 3
150000002367 halogens Chemical group 0.000 claims description 3
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 2
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 2
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 2
WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 claims description 2
239000012346 acetyl chloride Substances 0.000 claims description 2
229910052784 alkaline earth metal Inorganic materials 0.000 claims description 2
150000001342 alkaline earth metals Chemical class 0.000 claims description 2
239000011737 fluorine Substances 0.000 claims description 2
125000004970 halomethyl group Chemical group 0.000 claims description 2
229910052740 iodine Inorganic materials 0.000 claims description 2
239000011630 iodine Substances 0.000 claims description 2
QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 claims 1
150000007942 carboxylates Chemical class 0.000 claims 1
PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 claims 1
239000000126 substance Substances 0.000 claims 1
230000003110 anti-inflammatory effect Effects 0.000 abstract description 4
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 33
239000000203 mixture Substances 0.000 description 25
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 20
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 18
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 16
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 12
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
239000000243 solution Substances 0.000 description 12
239000002904 solvent Substances 0.000 description 11
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 10
239000004480 active ingredient Substances 0.000 description 10
239000000843 powder Substances 0.000 description 10
239000000377 silicon dioxide Substances 0.000 description 10
239000000443 aerosol Substances 0.000 description 9
239000002585 base Substances 0.000 description 9
GNOIPBMMFNIUFM-UHFFFAOYSA-N hexamethylphosphoric triamide Chemical compound CN(C)P(=O)(N(C)C)N(C)C GNOIPBMMFNIUFM-UHFFFAOYSA-N 0.000 description 9
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 8
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 8
OAIVIYSBZFEOIU-UHFFFAOYSA-N chloroform;propan-2-one Chemical compound CC(C)=O.ClC(Cl)Cl OAIVIYSBZFEOIU-UHFFFAOYSA-N 0.000 description 8
KWGKDLIKAYFUFQ-UHFFFAOYSA-M lithium chloride Chemical compound [Li+].[Cl-] KWGKDLIKAYFUFQ-UHFFFAOYSA-M 0.000 description 8
229910052708 sodium Inorganic materials 0.000 description 8
239000011734 sodium Substances 0.000 description 8
150000003431 steroids Chemical class 0.000 description 8
239000000725 suspension Substances 0.000 description 8
229940057995 liquid paraffin Drugs 0.000 description 7
239000000047 product Substances 0.000 description 7
CFKMVGJGLGKFKI-UHFFFAOYSA-N 4-chloro-m-cresol Chemical compound CC1=CC(O)=CC=C1Cl CFKMVGJGLGKFKI-UHFFFAOYSA-N 0.000 description 6
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 6
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 6
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
239000006260 foam Substances 0.000 description 6
238000009472 formulation Methods 0.000 description 6
230000000699 topical effect Effects 0.000 description 6
GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 5
239000002775 capsule Substances 0.000 description 5
239000013078 crystal Substances 0.000 description 5
239000008101 lactose Substances 0.000 description 5
239000007787 solid Substances 0.000 description 5
238000003756 stirring Methods 0.000 description 5
230000009885 systemic effect Effects 0.000 description 5
239000004338 Dichlorodifluoromethane Substances 0.000 description 4
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical class CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 4
PJGJQVRXEUVAFT-UHFFFAOYSA-N chloroiodomethane Chemical compound ClCI PJGJQVRXEUVAFT-UHFFFAOYSA-N 0.000 description 4
PXBRQCKWGAHEHS-UHFFFAOYSA-N dichlorodifluoromethane Chemical compound FC(F)(Cl)Cl PXBRQCKWGAHEHS-UHFFFAOYSA-N 0.000 description 4
235000019404 dichlorodifluoromethane Nutrition 0.000 description 4
239000000284 extract Substances 0.000 description 4
239000002674 ointment Substances 0.000 description 4
239000012188 paraffin wax Substances 0.000 description 4
239000002245 particle Substances 0.000 description 4
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
DZLFLBLQUQXARW-UHFFFAOYSA-N tetrabutylammonium Chemical class CCCC[N+](CCCC)(CCCC)CCCC DZLFLBLQUQXARW-UHFFFAOYSA-N 0.000 description 4
238000004809 thin layer chromatography Methods 0.000 description 4
238000011200 topical administration Methods 0.000 description 4
239000003981 vehicle Substances 0.000 description 4
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 3
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 3
239000008346 aqueous phase Substances 0.000 description 3
150000001663 caesium Chemical class 0.000 description 3
229960002242 chlorocresol Drugs 0.000 description 3
238000004587 chromatography analysis Methods 0.000 description 3
239000006071 cream Substances 0.000 description 3
238000005886 esterification reaction Methods 0.000 description 3
239000010410 layer Substances 0.000 description 3
210000004072 lung Anatomy 0.000 description 3
239000003921 oil Substances 0.000 description 3
235000019198 oils Nutrition 0.000 description 3
239000011541 reaction mixture Substances 0.000 description 3
229910000030 sodium bicarbonate Inorganic materials 0.000 description 3
235000017557 sodium bicarbonate Nutrition 0.000 description 3
FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 3
125000001424 substituent group Chemical group 0.000 description 3
239000002562 thickening agent Substances 0.000 description 3
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 3
CYRMSUTZVYGINF-UHFFFAOYSA-N trichlorofluoromethane Chemical compound FC(Cl)(Cl)Cl CYRMSUTZVYGINF-UHFFFAOYSA-N 0.000 description 3
VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 description 2
235000003911 Arachis Nutrition 0.000 description 2
244000105624 Arachis hypogaea Species 0.000 description 2
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
241001465754 Metazoa Species 0.000 description 2
241000699670 Mus sp. Species 0.000 description 2
FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 2
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
239000004133 Sodium thiosulphate Substances 0.000 description 2
229920002472 Starch Polymers 0.000 description 2
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
239000002253 acid Substances 0.000 description 2
239000003377 acid catalyst Substances 0.000 description 2
230000002378 acidificating effect Effects 0.000 description 2
208000010668 atopic eczema Diseases 0.000 description 2
JPOXNPPZZKNXOV-UHFFFAOYSA-N bromochloromethane Chemical compound ClCBr JPOXNPPZZKNXOV-UHFFFAOYSA-N 0.000 description 2
229910052792 caesium Inorganic materials 0.000 description 2
TVFDJXOCXUVLDH-UHFFFAOYSA-N caesium atom Chemical compound [Cs] TVFDJXOCXUVLDH-UHFFFAOYSA-N 0.000 description 2
FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 2
229940082500 cetostearyl alcohol Drugs 0.000 description 2
230000001419 dependent effect Effects 0.000 description 2
HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 2
239000002270 dispersing agent Substances 0.000 description 2
239000003995 emulsifying agent Substances 0.000 description 2
230000032050 esterification Effects 0.000 description 2
150000002148 esters Chemical class 0.000 description 2
125000004435 hydrogen atom Chemical group [H]* 0.000 description 2
239000006210 lotion Substances 0.000 description 2
GLDOVTGHNKAZLK-UHFFFAOYSA-N octadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCCCO GLDOVTGHNKAZLK-UHFFFAOYSA-N 0.000 description 2
238000007911 parenteral administration Methods 0.000 description 2
FDPIMTJIUBPUKL-UHFFFAOYSA-N pentan-3-one Chemical compound CCC(=O)CC FDPIMTJIUBPUKL-UHFFFAOYSA-N 0.000 description 2
VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical compound OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 description 2
229920001223 polyethylene glycol Polymers 0.000 description 2
229910000027 potassium carbonate Inorganic materials 0.000 description 2
238000001953 recrystallisation Methods 0.000 description 2
238000010992 reflux Methods 0.000 description 2
235000019980 sodium acid phosphate Nutrition 0.000 description 2
AJPJDKMHJJGVTQ-UHFFFAOYSA-M sodium dihydrogen phosphate Chemical compound [Na+].OP(O)([O-])=O AJPJDKMHJJGVTQ-UHFFFAOYSA-M 0.000 description 2
159000000000 sodium salts Chemical class 0.000 description 2
AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 2
235000019345 sodium thiosulphate Nutrition 0.000 description 2
239000008107 starch Substances 0.000 description 2
235000019698 starch Nutrition 0.000 description 2
239000000829 suppository Substances 0.000 description 2
239000000375 suspending agent Substances 0.000 description 2
OULAJFUGPPVRBK-UHFFFAOYSA-N tetratriacontyl alcohol Natural products CCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCO OULAJFUGPPVRBK-UHFFFAOYSA-N 0.000 description 2
QAEDZJGFFMLHHQ-UHFFFAOYSA-N trifluoroacetic anhydride Chemical compound FC(F)(F)C(=O)OC(=O)C(F)(F)F QAEDZJGFFMLHHQ-UHFFFAOYSA-N 0.000 description 2
ISBSSBGEYIBVTO-TYKWNDPBSA-N (20R,22R)-20,22-dihydroxycholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@@](C)(O)[C@H](O)CCC(C)C)[C@@]1(C)CC2 ISBSSBGEYIBVTO-TYKWNDPBSA-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
DDMOUSALMHHKOS-UHFFFAOYSA-N 1,2-dichloro-1,1,2,2-tetrafluoroethane Chemical compound FC(F)(Cl)C(F)(F)Cl DDMOUSALMHHKOS-UHFFFAOYSA-N 0.000 description 1
HIXDQWDOVZUNNA-UHFFFAOYSA-N 2-(3,4-dimethoxyphenyl)-5-hydroxy-7-methoxychromen-4-one Chemical compound C=1C(OC)=CC(O)=C(C(C=2)=O)C=1OC=2C1=CC=C(OC)C(OC)=C1 HIXDQWDOVZUNNA-UHFFFAOYSA-N 0.000 description 1
YCPXWRQRBFJBPZ-UHFFFAOYSA-N 5-sulfosalicylic acid Chemical compound OC(=O)C1=CC(S(O)(=O)=O)=CC=C1O YCPXWRQRBFJBPZ-UHFFFAOYSA-N 0.000 description 1
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208000035285 Allergic Seasonal Rhinitis Diseases 0.000 description 1
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 description 1
QCDFBFJGMNKBDO-UHFFFAOYSA-N Clioquinol Chemical compound C1=CN=C2C(O)=C(I)C=C(Cl)C2=C1 QCDFBFJGMNKBDO-UHFFFAOYSA-N 0.000 description 1
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CEAZRRDELHUEMR-URQXQFDESA-N Gentamicin Chemical compound O1[C@H](C(C)NC)CC[C@@H](N)[C@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](NC)[C@@](C)(O)CO2)O)[C@H](N)C[C@@H]1N CEAZRRDELHUEMR-URQXQFDESA-N 0.000 description 1
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HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 1
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230000001780 adrenocortical effect Effects 0.000 description 1
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239000004411 aluminium Substances 0.000 description 1
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CEGOLXSVJUTHNZ-UHFFFAOYSA-K aluminium tristearate Chemical compound [Al+3].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CEGOLXSVJUTHNZ-UHFFFAOYSA-K 0.000 description 1
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239000012267 brine Substances 0.000 description 1
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239000004359 castor oil Substances 0.000 description 1
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239000003729 cation exchange resin Substances 0.000 description 1
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239000003153 chemical reaction reagent Substances 0.000 description 1
239000003795 chemical substances by application Substances 0.000 description 1
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229960005228 clioquinol Drugs 0.000 description 1
238000007796 conventional method Methods 0.000 description 1
239000003246 corticosteroid Substances 0.000 description 1
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238000002425 crystallisation Methods 0.000 description 1
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FJBFPHVGVWTDIP-UHFFFAOYSA-N dibromomethane Chemical compound BrCBr FJBFPHVGVWTDIP-UHFFFAOYSA-N 0.000 description 1
229940042935 dichlorodifluoromethane Drugs 0.000 description 1
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XXJWXESWEXIICW-UHFFFAOYSA-N diethylene glycol monoethyl ether Chemical compound CCOCCOCCO XXJWXESWEXIICW-UHFFFAOYSA-N 0.000 description 1
CEALXSHFPPCRNM-UHFFFAOYSA-L disodium;carboxylato carbonate Chemical compound [Na+].[Na+].[O-]C(=O)OC([O-])=O CEALXSHFPPCRNM-UHFFFAOYSA-L 0.000 description 1
239000006196 drop Substances 0.000 description 1
239000003937 drug carrier Substances 0.000 description 1
230000000694 effects Effects 0.000 description 1
239000007920 enema Substances 0.000 description 1
229940079360 enema for constipation Drugs 0.000 description 1
SRCZQMGIVIYBBJ-UHFFFAOYSA-N ethoxyethane;ethyl acetate Chemical compound CCOCC.CCOC(C)=O SRCZQMGIVIYBBJ-UHFFFAOYSA-N 0.000 description 1
HWJHWSBFPPPIPD-UHFFFAOYSA-N ethoxyethane;propan-2-one Chemical compound CC(C)=O.CCOCC HWJHWSBFPPPIPD-UHFFFAOYSA-N 0.000 description 1
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
238000002474 experimental method Methods 0.000 description 1
125000001153 fluoro group Chemical group F* 0.000 description 1
125000003784 fluoroethyl group Chemical group [H]C([H])(F)C([H])([H])* 0.000 description 1
239000007789 gas Substances 0.000 description 1
229920000159 gelatin Polymers 0.000 description 1
239000008273 gelatin Substances 0.000 description 1
239000007903 gelatin capsule Substances 0.000 description 1
235000019322 gelatine Nutrition 0.000 description 1
235000011852 gelatine desserts Nutrition 0.000 description 1
239000003349 gelling agent Substances 0.000 description 1
ZEMPKEQAKRGZGQ-XOQCFJPHSA-N glycerol triricinoleate Natural products CCCCCC[C@@H](O)CC=CCCCCCCCC(=O)OC[C@@H](COC(=O)CCCCCCCC=CC[C@@H](O)CCCCCC)OC(=O)CCCCCCCC=CC[C@H](O)CCCCCC ZEMPKEQAKRGZGQ-XOQCFJPHSA-N 0.000 description 1
229940075507 glyceryl monostearate Drugs 0.000 description 1
239000008187 granular material Substances 0.000 description 1
150000008282 halocarbons Chemical class 0.000 description 1
238000004128 high performance liquid chromatography Methods 0.000 description 1
239000001257 hydrogen Substances 0.000 description 1
229910052739 hydrogen Inorganic materials 0.000 description 1
SHFJWMWCIHQNCP-UHFFFAOYSA-M hydron;tetrabutylazanium;sulfate Chemical compound OS([O-])(=O)=O.CCCC[N+](CCCC)(CCCC)CCCC SHFJWMWCIHQNCP-UHFFFAOYSA-M 0.000 description 1
230000004179 hypothalamic–pituitary–adrenal axis Effects 0.000 description 1
238000011065 in-situ storage Methods 0.000 description 1
230000004968 inflammatory condition Effects 0.000 description 1
230000002757 inflammatory effect Effects 0.000 description 1
230000004054 inflammatory process Effects 0.000 description 1
239000000543 intermediate Substances 0.000 description 1
239000007788 liquid Substances 0.000 description 1
229910052744 lithium Inorganic materials 0.000 description 1
229910052943 magnesium sulfate Inorganic materials 0.000 description 1
235000019341 magnesium sulphate Nutrition 0.000 description 1
230000014759 maintenance of location Effects 0.000 description 1
239000000463 material Substances 0.000 description 1
125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 1
LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 1
239000001788 mono and diglycerides of fatty acids Substances 0.000 description 1
XZLAHQGYFIXGJK-UHFFFAOYSA-N n-diaminophosphorylethanamine Chemical compound CCNP(N)(N)=O XZLAHQGYFIXGJK-UHFFFAOYSA-N 0.000 description 1
229960004927 neomycin Drugs 0.000 description 1
229910052757 nitrogen Inorganic materials 0.000 description 1
229960000988 nystatin Drugs 0.000 description 1
VQOXZBDYSJBXMA-NQTDYLQESA-N nystatin A1 Chemical compound O[C@H]1[C@@H](N)[C@H](O)[C@@H](C)O[C@H]1O[C@H]1/C=C/C=C/C=C/C=C/CC/C=C/C=C/[C@H](C)[C@@H](O)[C@@H](C)[C@H](C)OC(=O)C[C@H](O)C[C@H](O)C[C@H](O)CC[C@@H](O)[C@H](O)C[C@](O)(C[C@H](O)[C@H]2C(O)=O)O[C@H]2C1 VQOXZBDYSJBXMA-NQTDYLQESA-N 0.000 description 1
239000004006 olive oil Substances 0.000 description 1
235000008390 olive oil Nutrition 0.000 description 1
229940006093 opthalmologic coloring agent diagnostic Drugs 0.000 description 1
239000012044 organic layer Substances 0.000 description 1
239000003960 organic solvent Substances 0.000 description 1
125000004043 oxo group Chemical group O=* 0.000 description 1
239000008188 pellet Substances 0.000 description 1
239000002304 perfume Substances 0.000 description 1
239000008194 pharmaceutical composition Substances 0.000 description 1
239000000546 pharmaceutical excipient Substances 0.000 description 1
239000012071 phase Substances 0.000 description 1
239000002798 polar solvent Substances 0.000 description 1
229910052700 potassium Inorganic materials 0.000 description 1
239000011591 potassium Substances 0.000 description 1
239000003755 preservative agent Substances 0.000 description 1
239000003380 propellant Substances 0.000 description 1
RUOJZAUFBMNUDX-UHFFFAOYSA-N propylene carbonate Chemical compound CC1COC(=O)O1 RUOJZAUFBMNUDX-UHFFFAOYSA-N 0.000 description 1
QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 1
229960003415 propylparaben Drugs 0.000 description 1
239000008213 purified water Substances 0.000 description 1
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
150000003242 quaternary ammonium salts Chemical class 0.000 description 1
206010039083 rhinitis Diseases 0.000 description 1
239000000523 sample Substances 0.000 description 1
208000017520 skin disease Diseases 0.000 description 1
CDBYLPFSWZWCQE-UHFFFAOYSA-L sodium carbonate Substances [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 1
229910000029 sodium carbonate Inorganic materials 0.000 description 1
235000009518 sodium iodide Nutrition 0.000 description 1
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
239000012265 solid product Substances 0.000 description 1
238000001228 spectrum Methods 0.000 description 1
239000007921 spray Substances 0.000 description 1
239000002511 suppository base Substances 0.000 description 1
235000020357 syrup Nutrition 0.000 description 1
239000006188 syrup Substances 0.000 description 1
239000000454 talc Substances 0.000 description 1
229910052623 talc Inorganic materials 0.000 description 1
235000019364 tetracycline Nutrition 0.000 description 1
150000003522 tetracyclines Chemical class 0.000 description 1
229940040944 tetracyclines Drugs 0.000 description 1
238000002560 therapeutic procedure Methods 0.000 description 1
230000008719 thickening Effects 0.000 description 1
210000001541 thymus gland Anatomy 0.000 description 1
239000012049 topical pharmaceutical composition Substances 0.000 description 1
229940029284 trichlorofluoromethane Drugs 0.000 description 1
235000015112 vegetable and seed oil Nutrition 0.000 description 1
239000008158 vegetable oil Substances 0.000 description 1
239000001993 wax Substances 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J51/00—Normal steroids with unmodified cyclopenta(a)hydrophenanthrene skeleton not provided for in groups C07J1/00 - C07J43/00
- 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

Landscapes

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

CA321,032A 1978-02-08 1979-02-07 Antiinflammatory steroid of the androstane series Expired CA1129407A (en)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
GB5131/78		1978-02-08
GB513178		1978-02-08

Publications (1)

Publication Number	Publication Date
CA1129407A true CA1129407A (en)	1982-08-10

Family

ID=9790294

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
CA321,032A Expired CA1129407A (en)	1978-02-08	1979-02-07	Antiinflammatory steroid of the androstane series

Country Status (20)

Country	Link
JP (1)	JPS54145648A (de)
AT (1)	AT367771B (de)
AU (1)	AU520827B2 (de)
BE (1)	BE873996A (de)
CA (1)	CA1129407A (de)
CH (1)	CH639669A5 (de)
DE (1)	DE2904614A1 (de)
DK (1)	DK145578C (de)
ES (1)	ES477523A1 (de)
FI (1)	FI790403A7 (de)
FR (1)	FR2422688A1 (de)
IE (1)	IE47814B1 (de)
IL (1)	IL56613A (de)
IT (1)	IT1114534B (de)
NL (1)	NL7900967A (de)
NZ (1)	NZ189586A (de)
PT (1)	PT69192A (de)
SE (1)	SE435626B (de)
YU (1)	YU26779A (de)
ZA (1)	ZA79538B (de)

Families Citing this family (4)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
SE449106B (sv) *	1980-07-10	1987-04-06	Otsuka Pharma Co Ltd	Steroid med anti-inflammatorisk verkan samt komposition innehallande denna
US5237070A (en) *	1985-07-22	1993-08-17	Riker Laboratories, Inc.	Substituted DI-t-butylphenols
JP4847112B2 (ja) *	2005-11-29	2011-12-28	株式会社マキタ	園芸バリカン
US9290446B2 (en)	2010-10-27	2016-03-22	Hovione Inter Limited	Electrophilic reagents for monohalomethylation, their preparation and their uses

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
GB1384372A (en) *	1971-01-20	1975-02-19	Glaxo Lab Ltd	Dereivatives of 17alpha-hydroxyandrost-4-ene-17beta-carboxylic acids
GB1438940A (en) *	1972-07-19	1976-06-09	Glaxo Lab Ltd	17beta-haloalkoxycarbonyl-17alpha-oxysteroids

1979
- 1979-02-06 IT IT47909/79A patent/IT1114534B/it active
- 1979-02-07 IE IE236/79A patent/IE47814B1/en unknown
- 1979-02-07 JP JP1317379A patent/JPS54145648A/ja active Pending
- 1979-02-07 BE BE0/193318A patent/BE873996A/xx not_active IP Right Cessation
- 1979-02-07 DK DK50179A patent/DK145578C/da active
- 1979-02-07 NL NL7900967A patent/NL7900967A/xx not_active Application Discontinuation
- 1979-02-07 CA CA321,032A patent/CA1129407A/en not_active Expired
- 1979-02-07 ZA ZA79538A patent/ZA79538B/xx unknown
- 1979-02-07 PT PT7969192A patent/PT69192A/pt unknown
- 1979-02-07 CH CH121779A patent/CH639669A5/de not_active IP Right Cessation
- 1979-02-07 DE DE19792904614 patent/DE2904614A1/de not_active Withdrawn
- 1979-02-07 IL IL56613A patent/IL56613A/xx unknown
- 1979-02-07 FR FR7903085A patent/FR2422688A1/fr active Granted
- 1979-02-07 ES ES477523A patent/ES477523A1/es not_active Expired
- 1979-02-07 AT AT0092379A patent/AT367771B/de not_active IP Right Cessation
- 1979-02-07 SE SE7901100A patent/SE435626B/sv unknown
- 1979-02-07 YU YU00267/79A patent/YU26779A/xx unknown
- 1979-02-07 NZ NZ189586A patent/NZ189586A/xx unknown
- 1979-02-07 FI FI790403A patent/FI790403A7/fi unknown
- 1979-02-08 AU AU44084/79A patent/AU520827B2/en not_active Ceased

Also Published As

Publication number	Publication date
DK145578B (da)	1982-12-13
PT69192A (en)	1979-03-01
IL56613A (en)	1982-12-31
DE2904614A1 (de)	1979-08-09
AU4408479A (en)	1979-08-16
NL7900967A (nl)	1979-08-10
AT367771B (de)	1982-07-26
DK50179A (da)	1979-08-09
IT1114534B (it)	1986-01-27
BE873996A (fr)	1979-08-07
IE47814B1 (en)	1984-06-27
IT7947909A0 (it)	1979-02-06
CH639669A5 (en)	1983-11-30
DK145578C (da)	1983-05-09
JPS54145648A (en)	1979-11-14
YU26779A (en)	1983-01-21
FR2422688A1 (fr)	1979-11-09
IL56613A0 (en)	1979-05-31
FR2422688B1 (de)	1982-07-16
SE7901100L (sv)	1979-08-09
AU520827B2 (en)	1982-03-04
ES477523A1 (es)	1979-07-16
SE435626B (sv)	1984-10-08
ZA79538B (en)	1980-02-27
FI790403A7 (fi)	1979-08-09
IE790236L (en)	1979-08-08
ATA92379A (de)	1981-12-15
NZ189586A (en)	1981-01-23

Legal Events

Date	Code	Title	Description
1999-08-10	MKEX	Expiry

Publication	Publication Date	Title
US4093721A (en)	1978-06-06	Pharmaceutical compositions of 6α,9α-difluoro-androst-4-ene-17β-carboxylates and derivatives thereof
US4335121A (en)	1982-06-15	Androstane carbothioates
US4188385A (en)	1980-02-12	Thioetianic acid derivatives
US4242334A (en)	1980-12-30	Corticoid 17-(alkyl carbonates) and processes for their preparation
US4267173A (en)	1981-05-12	Use of 6β-fluoro-7α-halogenocorticoids as topical anti-inflammatories and pharmaceutical formulations useful therefor
FI80888C (fi)	1990-08-10	Foerfarande foer framstaellning av terapeutiskt verkande steroida karboxylsyraestrar.
GB2088877A (en)	1982-06-16	Androstane 17 beta carbothioates
US4172132A (en)	1979-10-23	1,3,5(10),6,8,14-19-Nor-pregnahexaenes, their use as anti-psoriatic agents, and pharmaceutical formulations useful therefor
US4187301A (en)	1980-02-05	17 Beta-thiocarboxylic acid esters of 6 alpha, 6 beta-difluoro-3-oxoandrost-4-enes
IL38589A (en)	1976-06-30	11beta-hydroxy-17alpha-acyloxy-3-oxo-androst-4-ene-17beta-carboxylic acid esters
HK68487A (en)	1987-10-02	Aromatic heterocyclic esters of steroids, their preparation and pharmaceutical compositions containing them
PL186637B1 (pl)	2004-02-27	Pochodne androstenu, kompozycje farmaceutyczne zawierające je oraz ich zastosowanie
CS209919B2 (en)	1981-12-31	Method of making the esters of the 4-halogen-9-fluor-3-oxo-androst-4-en and 4-halogen-9-fluor-3-oxoandrosta -1,4-dien-17beta-thiocarboxyl acid
EP0143764B1 (de)	1990-06-27	Androstan-17beta-Carbonsäureester, ein Prozess und Zwischenprodukte für ihre Herstellung, Kompositionen und Methode zur Behandlung inflammatorischer Zustände
CA1278293C (en)	1990-12-27	Androstane-17 beta-carboxylic acid esters
CA1129407A (en)	1982-08-10	Antiinflammatory steroid of the androstane series
IE43452B1 (en)	1981-02-25	Terpenoid esters of steroids
IE41663B1 (en)	1980-02-27	Alkyl and haloalkyl androst-4-ene and androsta-1,4-diene17-carboxylates
JPS6043358B2 (ja)	1985-09-27	９α−ハロ−１８−メチル−２１−デスオキシプレドニンロンのエステル類の製造法
US4655971A (en)	1987-04-07	Novel process for the preparation of steroidal esters
US4427671A (en)	1984-01-24	Steroids esterified in position 17 and thioesterified in position 21, a process for preparing them and their use as medicaments
GB1563638A (en)	1980-03-26	21-halogenopregnane compounds
US3845085A (en)	1974-10-29	Steroids of the pregnane series
US4011315A (en)	1977-03-08	21-acetals and mixed acetals of steroidal 21-aldehydes, intermediates and methods of preparation
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