GB1113851A - Decoyinine derivatives - Google Patents

Abstract

Triacyl derivatives of the antibiotic decoyinine having the formula <FORM:1113851/C2/1> wherein R is selected from hydrocarbon carboxylic acyl of from 9 to 12 carbon atoms inclusive, halo-, nitro-, hydroxy-, amino-, cyano-, thiocyano-and lower-alkoxy (C1 to C6 inclusive) -substituted hydrocarbon carboxylic acid acyl of from 2 to 12 carbon atoms inclusive and lower-alkoxy (C1 to C6 inclusive) carbonyl, are prepared by a process similar to that described in Specification 985,162 for preparing the decoyinine triacylates disclosed therein. Triacyl derivatives of the above formula may be hydrogenated (see also Specification 985,162) to produce dihydrodecoyinine triacylates of the formula <FORM:1113851/C2/2> wherein R is as above defined and deoxydihydrodecoyinine diacylates of the formula <FORM:1113851/C2/3> wherein R is as above defined. Dihydrodecoyinine and deoxydihydrodecoyinine (prepared by the deacylation of dihydrodecoyinine triacylates and dihydrodecoyinine diacylates and separation of the resulting mixture) can be acylated to produce dihydrodecoyinine tetra- and pentaacylates of the formula <FORM:1113851/C2/4> and deoxydihydrodecoyinine tri- and tetraacylates of the formula <FORM:1113851/C2/5> wherein R is selected from hydrocarbon carboxylic acid acyl of from 2 to 12 carbon atoms, inclusive; halo-, nitro-, hydroxy-, amino-, cyano-, thiocyano-, and lower alkoxy-substituted hydrocarbon carboxylic acid acyl of from 2 to 12 carbon atoms inclusive; and lower alkoxy (C1 to C6 inclusive) carbonyl; and R1 is selected from hydrogen and hydrocarbon carboxylic acid acyl of from 2 to 12 carbon atoms inclusive; halo-, nitro-, hydroxy-, amino-, cyano-, thiocyano-, and lower alkoxy-substituted hydrocarbon carboxylic acid acyl of from 2 to 12 carbon atoms inclusive; and lower alkoxy (C1 to C6 inclusive) carbonyl.ALSO:Acylates of the antibiotic decoyinine and its derivatives dehydrodecoyinine and deoxydihydrodecoyinine (see Division C2) comprise the active ingredients of pharmaceutical compositions. The compositions contain a pharmaceutically acceptable carrier and may be administered orally, parenterally or applied topically in the form of tablets, effervescent tablets, powders, granules, capsules, solutions and suspensions (these may be sterile and include aqueous suspensions and oil suspensions especially those containing edible oil) ointments, creams, water-oil emulsions, lotions and baugies. The compositions have bactericidal activity and may also contain sulpha compounds (e.g. sulphadiazine, sulphamerazine, sulphanilamide, sulphamethazine, sulphacetamide and sulphamethylthiadiazole); other antibiotics (e.g. tetracycline, oxytetracyline, chlotetracycline, penicillins, novobiocin, neomycin, psicofuranine, erythromycin, streptomycin, bacitracin, polymyxin, chloramphenical, kanamycin, nystatin and streptozotocin); vitamins (e.g. thiamine, riboflavin, ascorbic acid, niacinamide, pyridoxine, pantothenic acid or pantothenate salts, vitamin B1Z and folic acid); corticoids (e.g. cortisone, hydrocortisone, prednisone and prednisolone, including esters thereof, e.g. the acetate, cyclo pentylpropionate, succinate and the sodium salt, and the fluoro, methyl, and hydroxy analogues thereof such as 6a -fluorohydrocortisone, 16 - hydroxy - 9a - fluorohydrocortisone and 16 - methyl - 9a - fluoroprednisolone, and the esters thereof).