GB1354097A - Isoxazole derivatives - Google Patents

Abstract

1354097 Naphth-[1,2-c]isoxazoles TEIKOKU HORMONE MFG CO Ltd 23 April 1971 [24 April 1970 (3) 30 Jan 1971 16 March 1971 19 March 1971 20 March 1971 (2) 20 April 1971] 11063/71 Heading C2C Novel naphth-[1,2-c] isoxazoles of the general formula wherein ring A is optionally substituted, ring B optionally contains a 4,5-double bond and R is a methyl, hydroxymethyl, (optionally substituted alkoxy) methyl, (optionally substituted amino)- alkoxymethyl, halomethyl, (optionally substituted amino)-methyl or cyano group or a group of the formula -C(=Y)-R 1 , where R 1 is a hydroxy, optionally substituted amino or C 1-12 hydrocarbyloxy or hydrocarbyl group, or a group of the formula -OM1/12, where M is an alkali metal, alkaline earth metal or aluminium atom, an ammonium group or an organic base cation and n is the valency of M, or a group of formula -O(AlOH)¢, and Y is an oxygen or sulphur atom, Y being an oxygen atom when R 1 is a hydroxy, hydrocarbyloxy or -OM1/12 group, and acid addition salts thereof are prepared (a) by cyclization of a 1-hydroxylimino-1,2-dihydronaphthalene of the general formula wherein ring B<SP>1</SP> optionally contains a 3,4-double bond; (b) when R is a -COOH group by hydrolysis or hydrogenolysis of the corresponding compound in which R is -COR 1 and R 1 is a hydrocarbyloxy group or hydrolysis of the corresponding compound in which R is a cyano or COR 1 group and R 1 is an optionally substituted amino group; (c) when R is a -COOM1/12 or -COO(AlOH)¢ group, by reaction of the corresponding compound in which R is a -COOH group with an alkali metal, alkaline earth metal or aluminium hydroxide or alkoxide, an organometallic compound containing a bond between an alkali or alkaline earth metal or aluminium and carbon, ammonia or an organic base; (d) when R is a -COR 1 group and R 1 is an optionally substituted amino group, by reaction of the corresponding compound in which R is a -COOH group or a functional derivative thereof (e.g. the acid halide or acid anhydride, the latter being produced from the free acid by dehydration with ammonia or an amine, or when R is a -CONH 2 group, by partial hydrolysis of the corresponding compound in which R is a cyano group; (e) when R is a -CS-R 1 group, by conversion in a manner known per se of the corresponding compound in which R is a -CO-R 1 group; (f) when R is a hydroxymethyl group, by hydrogenation of the corresponding compound in which R is a -COOH or -CO-R 1 group and R 1 is a hydrocarbyloxy group; (g) when R is a halomethyl group, by conversion in a manner known per se of the corresponding compound in which R is a hydroxymethyl group; (h) when R is a methyl group, by hydrogenation of the corresponding compound in which R is a halomethyl group; (i) when R is an (optionally substituted alkoxy)-methyl or (optionally substituted amino) alkoxymethyl group, by reaction of the corresponding compound in which R is a halomethyl group with an alkali metal (optionally substituted) alkoxide or (optionally substituted amino)-alkoxide; (j) when R is an (optionally substituted amino)- methyl group, by reaction of the corresponding compound in which R is a halomethyl or ptoluene sulphonyloxymethyl group (the sulphonates being produced by reaction of the corresponding compound in which R is a hydroxymethyl group with p-toluenesulphonyl chloride) with ammonia, an amine or an amine alkali metal salt or by hydrogenation of the corresponding compound in which R is a -CO-R 1 group and R 1 is an optionally substituted amino group; (k) when R is a cyano group, by dehydration of the corresponding compound in which R is a -CONH 2 group; and (1) when R is a COR 1 group and R 1 is a hydrocarbyloxy group by esterification of the corresponding compound in which R 1 is a hydroxy group, e.g. via the corresponding acid halide; followed optionally by salification of the resulting free base with an acid. Pharmaceutical compositions having antiphlogistic, gastric juice secretion inhibiting and anti-ulcer activity comprise, as active ingredient, a naphth-(1,2-c] isoxazole of the first general formula above or an acid addition salt thereof, together with a pharmaceutically acceptable carrier or diluent.