GB994611A - Improvements in or relating to therapeutically active iodine-substituted aromatic compounds and compositions containing them - Google Patents

Abstract

The invention comprises compounds of the general formula <FORM:0994611/C2/1> in which (a) R1 and R2 are methyl, R, R3, R4 and R5 are H and n is 1; (b) R and R2 are methyl, R0 and R4 are H, R and R5 are acetyl groups and n is 1; (c) R, R1 and R2 are methyl, R3, R4 and R5 are H and n is 1; and (d) R1 and R2 are methyl, R and R4 are H, R5 is a phosphono group and n is 1. These compounds and compound of the above formula, in general, in which R is H, C1-C4 alkyl or acyl derived from a C2-C4 alkanoic acid, R1 and R2 are H, C1-C4 alkyl or halogen; R3 and R4 are hydrogen or C1-C4 alkyl; R5 is hydrogen, phosphor or acyl derived from a C2-C4 alkanoic acid and n is 0-3 are prepared by reducing the corresponding compound in which the group -CH2OR5 is replaced by COOH with diborane in the presence of an inert solvent and at a temperature of from - 20 DEG to 50 DEG C. to give the corresponding alcohol and reacting this with an acylating agent derived from a C2-C4 alkanoic acid to give the acyl derivative or converting it to the phosphate ester, if desired. The phosphate ester is obtained by reacting one molar proportion of the alcohol with two molar proportions of 2-cyanoethyl phosphate in the presence of anhydrous pyridine and 8 molar proportions of dicyclhexylcarbdiimide and subjecting the product to alkaline hydrolysis at about 100 DEG C. Suitable acylating agents are, for example, alkanoyl halides and alkanoic anhydrides.ALSO:A hypocholesteremic composition comprises as principal active ingredient a compound having the general formula <FORM:0994611/A5-A6/1> in which R is hydrogen, C1-C4 alkyl or an acyl group derived from a C2-C4 alkanoic acid; R1 and R2 are hydrogen, C1-C4 alkyl or halogen; R3 and R4 are hydrogen or C1-C4 alkyl, R5 is hydrogen, phosphono or an acyl group derived from a C2-C4 alkanoic acid, and n is 0-3, dispersed in a pharmaceutically acceptable carrier. In addition to the above compounds other therapeutic compounds may be present e.g. other hypocholesteremic agents such as 22,25-dicyacholestanol, the D-isomer of 3,5,31-triidothyronine, sodium D-thyroxine and sodium L-thyroxine; glucocorticoids such as hydrocortisone, p prednisolone, 6a - fluoroprednisonole and 6a - methylprednisolone; anticoagulants such as heparin, 2-diphenylacetyl-1,3-indandione, polyethylene sulphonate and dicumarol and its derivatives; vitamins such as nicotinic acid, ascorbic acid, mixed tocopherols, Vitamin B12 and pyridoxine hydrochloride; estrogens such as estradiol and ethinyl estradiol; androgens such as testosterone, methyl testosterone and fluoxymesterone; combinations of estrogens and androgens such as estradiol and testosterone; unsaturated fatty acids or esters such as safflower oil, lecithin, corn oil and linoleic acid and esters; antibiotics such as neomycin; ion-exchange resins such as cholestylamine; analgesics such as aspirin; hypoglycemic agents such as tolbutamide; compounds associated with cholesterol synthesis or metabolism such as a -phenylbutyric acid, a - p - biphenylbutyric acid and ethyl a - Cp - chlorophenoxy) isobutyrate; lipotrophic agents such as choline and inositol; amino acids such as dl-methionine, taurine and glycine; sterols such as sitosterol; diuretics such as ethoxzolamide, acetazolamide and hydrochlorothiazide; anovexigenic agents such as amphetamine; and cardiovascular agents (including vasodilators and hypotensive agents) such as chlorisond amine chloride, hexamethonium chloride and pentaerythritol tetranitrate. The compositions may be administered in the form of tablets, pills, capsules, powders, wafers, cachets, granules, sterile parenteral solutions or suspensions in aqueous or oil vehicles or in oral aqueous or oil dispersions.