GB872108A - Improvements in or relating to steroids and the manufacture thereof - Google Patents

Abstract

The invention comprises 1-dehydro-6,21-difluoro-9a -halo-21-desoxy-hydrocortisone, 1-dehydro - 6,21 - difluoro - 9a - halo - 21 - desoxycortisone, compounds having the formulae <FORM:0872108/IV (b)/1> <FORM:0872108/IV (b)/2> wherein R is a hydrocarbon radical containing from 1-10 carbon atoms inclusive, X is fluorine, chlorine or bromine and R1 is a keto or hydroxy group and a process which comprises treating 6-fluoro-9a -halo-11b ,17a ,21-trihydroxy-1,4-pregnadiene-3, 20-dione with an alkyl or aryl sulphonyl halide to obtain the corresponding 21-alkyl or aryl sulphonate of 6-fluoro-9a -halo - 11b ,17a ,21 - trihydroxy - 3,20 - dione and thereafter treating the thus-obtained 21-alkyl or aryl sulphonate with a metal fluoride to obtain the corresponding 6,21-difluoro-9a -halo-11b ,17a - dihydroxy - 1,4 - pregnadiene - 3,20 - dione, which may be oxidised to give 6,21-difluoro - 9a - halo - 1,4 - pregnadiene - 3,11,20 - trione. Alternatively the 21-alkyl or aryl sulphonate may be reacted with an iodinating agent such as sodium iodide to obtain a 21-iodo compound which is subsequently fluorinated. Alternatively the 11-keto compound may be employed as starting material and the oxidation step omitted. In another method fluorination at carbon atom 21 is first carried out followed by halogenation at carbon atom 9. Both the 6a and 6b -epimers may be employed, the 6a -epimer being convertible to the 6b -epimer by treatment with an anhydrous mineral acid e.g. HCl. Illustrative products of the invention are 1-dehydro-6a ,9a ,21-trifluoro 21 - desoxyhydrocortisone, 1 - dehydro - 6a ,21 - difluoro - 9a - chloro - 21 - desoxyhydrocortisone, 1 - dehydro - 6a ,21 - difluoro - 9a - bromo - 21-desoxyhydrocortisone, 1-dehydro-6a ,9a ,21-trifluoro-21-desoxycortisone, 1-dehydro-6a ,21-difluoro-9a -chloro-21-desoxycortisone, and 1-dehydro - 6a ,21 - difluoro - 9a - bromo - 21 - desoxycortisone. Specification 850,833 is referred to.ALSO:Pharmaceutical compositions comprise 1-dehydro - 6,21 - difluoro - 9a - halo - 21 - desoxy-cortisone or 1-dehydro-6,21-difluoro-9a -halo-21-desoxyhydrocortisone and a pharmaceutical diluent. They are employed orally as pills, tablets, capsules, syrups and elixirs, in liquid forms for injectable products and topically as ointments, creams and lotions with or without coacting antibiotics and germicides. Specification 850,833 is referred to.