GB883324A - New benzoxazine derivatives, their preparation and pharmaceutical compositions containing them - Google Patents

Abstract

The invention comprises compounds of the general formula <FORM:0883324/IV (b)/1> in which R is hydrogen or a lower alkyl radical (i.e. containing less than four carbon atoms), R1 is hydrogen or a lower alkyl or lower alkoxy radical, R11 is hydrogen, an acyl group or a lower alkyl radical, together with processes for their preparation (a) by reacting a 2,2-dihalo-3-oxo-dihydro-1,4-benzoxazine with a compound of formula <FORM:0883324/IV (b)/2> (which is unsubstituted in the position para to OR11, and in which R1 and R11 are as defined above), any free OH groups being alkylated or acylated if desired during or after the reaction; (b) by reacting an a ,a -disubstituted glycollic acid of formula <FORM:0883324/IV (b)/3> (R111 is alkyl, aralkyl or other group which can be replaced by hydrogen) or a reactive ester thereof with an R-substituted o-aminophenol, and if necessary subsequently converting R111 into R11; (c) by ring closure of an a ,a -disubstituted glycollic acid o-hydroxyanilide of formula <FORM:0883324/IV (b)/4> The intermediate anilides are prepared by reaction of an R-substituted 2,3-dioxo-dihydro-1,4-benzoxazine with an organomagnesium halide of formula <FORM:0883324/IV (b)/5> or by reaction of an o-hydroxyphenyl oxamic acid ester of formula <FORM:0883324/IV (b)/6> (COOA is a reactive ester group) with the above Grignard reagent, or by reacting an a ,a -disubstituted-a -halo-acetyl halide corresponding to the glycollic acid V with an R-substituted o-aminophenol. The intermediate 2,2 - dihalo - 3 - oxo - dihydro-1,4-benzoxazines are prepared by halogenation of an R-substituted-2,3-dioxo-dihydro-1,4-benzoxazine. The oxamic acid esters are prepared by reacting an oxalic acid alkyl ester chloride with an o-aminophenol. a -Chloro-a ,a -bis (p-methoxyphenol) acetyl chloride is prepared from p-anisilic acid and PCl5.ALSO:Pharmaceutical compositions having laxative properties comprise benzoxazines of formula <FORM:0883324/VI/1> (in which R represents H or alkyl, R1 is H, alkyl or alkoxy and R11 is H, acyl or alkyl, the alkyl and alkoxy groups containing from one to three carbon atoms) together with a carrier. The compositions may take the form of tablets, dragees, emulsions, suspensions, granulates, suppositories and examples detail the formation of compositions of each type.