GB973359A - New triazolidines, their manufacture and use - Google Patents

Abstract

The invention comprises compounds of general formula <FORM:0973359/C1/1> in which R1 represents a hydrogen or halogen atom or an alky or alkoxy group containing 1 to 4 carbon atoms, and R2 represents a hydroxyl group, a halogen atom, an alkoxy group containing 1 to 4 carbon atoms, a halogeno-alkoxy or hydroxy-alkoxy group containing up to 4 carbon atoms, an unsubstituted phenoxy or benzyloxy group or a phenoxy or benzyloxy group in which the phenyl nucleus is substituted by a halogen atom or by an alkyl or alkoxy group containing up to 4 carbon atoms, or an aliphatic acylamino group containing up to 4 carbon atoms: and their physiologically tolerable salts with an inorganic or organic base: and their preparation by the methods described, these comprising (1) treatment of a reactive functional derivative of a compound of formula <FORM:0973359/C1/2> or <FORM:0973359/C1/3> with an alkaline agent, or heating such a compound, (2) reaction of a compound of formula <FORM:0973359/C1/4> or <FORM:0973359/C1/5> with a reactive derivative of carbonic acid, (3) reaction of a functional derivative of a compound of formula <FORM:0973359/C1/6> with a compound of formula <FORM:0973359/C1/7> to form an intermediate 11 or 11a and continuing as under (1), (4) reaction of a functional derivative of a compound of formula <FORM:0973359/C1/8> or <FORM:0973359/C1/9> with a phenyl-urea or phenyl-carbamic acid ester or halide corresponding to an amine V, (5) reaction of a compound of formula <FORM:0973359/C1/100> with an amine V in the presence of a reactive derivative of carbonic acid, (6) replacement of the sulphur atom in a compound of formula <FORM:0973359/C1/111> by an oxygen atom by use of an oxidation agent or heavy metal oxide, (7) reaction of a compound of formula <FORM:0973359/C1/122> with an amine V, and (8) reaction of a compound of formula <FORM:0973359/C1/133> with an amine V. Semicarbazide carboxylic acids II and IIa and derivatives (e.g. methyl and ethyl esters) may be obtained by the first step of (3) above or by reaction of phenylhydrazine monocarboxylic acid derivatives with phenyl isocyanates; 1-phenyl-4-(p-ethoxyphenyl)-semicarbazide - carboxylic acid-(1) ethyl ester is prepared from the semicarbazide using chloracetic acid ethyl ester. 1-Phenyl-4-(4-ethoxyphenyl)-3-oxo-5-thio-1,2,4-triazolidine is prepared by reaction of phenylhydrazine-b -carboxylic acid-ethyl ester-a -thiocarboxylic acid chloride with p-phenetidine followed by treatment with sodium hydroxide solution. 5-Ethoxy-3-phenyl-1, 3, 4-oxadiazolone-(2) is prepared by reaction of ammonia with phenylhydrazine-b -carboxyli acid-ethyl ester-a -carboxylic acid chloride. Pharmaceutical compositions comprise compounds I and salts of the invention in admixture or conjunction with a pharmaceutically suitable carrier. Oral and parenteral administration is mentioned (tablets, dragees, capsules, solutions, suspensions). The compounds have anti-phlogistic, analgesic, hypotensive and vasodilatory action.