GB1037642A - Pharmaceutical compositions containing 3,5-disubstituted isoxazoles - Google Patents

Abstract

The invention comprises complexes of formula <FORM:1037642/C2/1> wherein n is 1 or 2 and MS is a metal salt, and their preparation by reaction of the complex components. 5 - Carboxy - 3 - methyl - isoxazole is prepared by reaction of acetopyruvic acid and hydroxylamine hydrochloride. 3 - Carboxy - 5 - methyl - isoxazole is prepared by reaction of acetonylacetone and nitric acid. 5 - Carbamoyl - 3 - methyl - isoxazole is prepared by reaction of 5-carboxy-3-methyl isoxazole with thionyl chloride and concentrated ammonium hydroxide.ALSO:Pharmaceutical compositions having hypoglycemic activity comprise (a) a compound of formula <FORM:1037642/A5-A6/1> wherein n is 1 or 2 and MS is a metal salt, in combination with a pharmaceutical carrier, or (b) a compound of formula <FORM:1037642/A5-A6/2> wherein R1 and R2 are C1-4 alkyl, carboxyl, C1-4 alkyl carboxylate, carbamoyl or C1-4 alkyl substituted carbamoyl groups, dispersed in a solid carrier or in a liquid carrier in which the active ingredient is insoluble. Dosage forms specified one for oral or parenteral commistration, e.g. tablets, pills, capsules, powders, wafers, cachets, elixirs, granules, suspensions or emulsions. Other pharmaceutically active compounds may be present, for example other hypoglycemic agents, such as tolbutamide, chlorpropamide, plenformin hydrochloride, mesoxalic and, insulin, nicotinic acid, triparanol, the D. isomer of 3, 5, 31-tri-codothyronine, triodothyropropionic acid, sodium L-thyroxine, and sodium D-thyroxine, glucocorticoids, such as hydrocortisone, prednisolone and 6a -methyl-prednisolone, anti-coagulants such as heparin, 2-diphenylacetyl-1, 3-indandione, polyethylene sulphonate and dicoumarol or its derivatives, vitamins such as nicotinic acid, vitamin B12, ascorbic acid or pyridoxine hydrochloride, esterogens, such as estradiol, androgens, such as testosterone, unsaturated fatty acids such as corn oil and linoleic acid or esters, antibiotics such as neomycin, analgesics such as aspirin, compounds associated with cholesteral synthesis or metabolism such as a -phenyl-butyric acid and a -p-biphenylylbutyric acid, lipotrophic agents such as choline and inosital, amino-acids such as taurine and glycine, sterols such as sitosterol, diuretics such as acetazolamide and chlorothiazide, anorexigenic agents such as amphetamine, and cardiovascular agents such as chlorisodamine chloride, hexamethonium chloride and pentaerythritol tetranitrate.