GB907812A - Improvements in or relating to steroids and the manufacture thereof - Google Patents

Abstract

The invention comprises compounds having the formulae <FORM:0907812/IV (b)/1> wherein X is chlorine or fluorine, X11 is bromine, chlorine, fluorine or iodine, R2 is a b -hydroxy or a keto group, X111 is chlorine, fluorine, bromine, iodine or hydrogen, R4 is the sulphonyl radical of a hydrocarbon sulphonic acid containing 1-12 carbon atoms; 21-esters thereof of hydrocarbon carboxylic acids containing 1-12 carbon atoms and processes for the preparation thereof by dehydrating a 2 - halo - 11b ,17a ,21 - trihydroxy-4-pregnene-3,20-dione 21-acylate to obtain a 4,9(11)-pregnadiene II, treating II with hypohalous acid gives a 9a -halo compound III, III is treated with a base to give a 9b ,11b -epoxy compound IV which with HF gives 2,9a -difluoro-17a ,21-dihydroxy-4-pregnene - 3,11,20-trione 21-acylate V; V is treated with an organic sulphonyl halide to produce a 21-sulphonate ester VIII, VIII with sodium iodide gives a 21-iodo compound IX which on treatment with silver fluoride gives 2,21-difluoro17a -hydroxy-4-pregnene - 3,11,20 - trione. The 11b -hydroxy group when present may be oxidised to an 11-keto group. Alternatively the 21-sulphonate is reacted directly with potassium fluoride to obtain the 21-fluoro compound. Illustrative products of the invention are 2,9a - difluoro - 11b ,17a ,21 - trihydroxy - 4 - pregnene-3,20-dione 21-acetate, 2,9a -difluoro-11b ,17a ,21-trihydroxy-4-pregnene - 3,20 - dione and 2,21-difluoro-11b ,17a -dihydroxy - 4 - pregnene-3,20-dione.ALSO:Pharmaceutical compositions comprise compounds having the formula <FORM:0907812/VI/1> wherein X11 is bromine, chlorine, fluorine or iodine, and R2 is a b -hydroxy or a keto group, 21-esters thereof of hydrocarbon carboxylic acids containing 1-12 carbon atoms, inclusive, or compounds having the formula <FORM:0907812/VI/2> wherein X111 is chlorine, fluorine, bromine, iodine or hydrogen, and X is chlorine or fluorine, and a pharmaceutical diluent. They are employed orally as tablets, parenterally, or topically as ointments, lotions, creams, jellies, suppositories, bougies, and aqueous suspensions. An ointment incorporating 2,9-difluoro-11b , 17a , 21 - trihydroxy - 4 - pregnene - 3,20 - dione may contain in addition neomycin sulphate. Alternatively, novobiocin, bacitracin, circulin, polymyxin B sulphate, gramicidin, streptomycin, dihydrostreptomycin sulphate, oxytetracylcine, chlortetracylcine, tetracycline, chloramphenicol, and the sulphonamides may be used.