GB964050A - New hydrazides and process for manufacturing same - Google Patents

Abstract

The invention comprises compounds of the formula: <FORM:0964050/C1/1> and salts thereof, wherein R is hydrogen or a lower alkyl group, R1 and R2 are each hydrogen or a lower aliphatic group or together represent a doubly linked straight or cyclic aliphatic group, or one is hydrogen and the other is the acyl radical of a lower aliphatic carboxylic acid, R3 is hydrogen or a lower aliphatic group or a lower aliphatic acyl group, R31 is hydrogen or a lower aliphatic group, R4 is a lower aliphatic hydrocarbon group which may be substituted by a free hydroxy, amino or mercapto groupo or a halogen atom or interrupted by a hetero atom, or is a lower aliphatic acyl group, R5 is hydrogen or a lower aliphatic hydrocarbon group, as defined for R4, and R6, is hydrogen, lower alkyl, lower alkoxy or halogen (the word "lower" indicating a group of 1-7 carbon atoms and the word "halogen" being understood to include the trifluoromethyl group). The compounds are prepared by reacting a lower alkyl ester of the appropriate 5-sulphamyl-2-amino-benzoic acid with hydrazine or the appropriate substituted hydrazine, or by reacting a 5-sulphamyl-2-chlorobenzoic hydrazide with ammonia or an amine HNR3R3, and, if desired, effecting the introduction or conversion of substituents, in accordance with the formula of the final products, in a known manner, e.g. by acylation, hydrolysis, alkylation, conversion to a hydrazone by reaction with a ketone and reduction of a hydrazone to give a radical linked by a single bond. Preferred products comprise compounds wherein R1 and R2 are hydrogen, methyl or hydroxysulphonylmethyl or R1 and R2 together form an alkylidene, azacycloalkylidene e.g. N-substituted piperidylene-(4), or oxa-, aza- or thia-cycloalkyl-alkylidene, e.g. 1-morpholino- or 1-piperidino-propylidene-(2), group; R3 and R31 are hydrogen, methyl, ethyl, hydroxyethyl, isopropyl, n-butyl or acetyl; R4 is methyl, ethyl, isopropyl or hydroxyethyl; R5 is hydrogen, methyl, ethyl or hydroxyethyl and the benzene ring is unsubstituted or bears a methyl substituent. Dimethylsulphamylanthranilic acid methyl ester is made by treating 2-chlorobenzoic acid-5-sulphonyl chloride with dimethylamine, reacting the resulting 5-dimethylsulphamyl-2-chlorobenzoic acid with ammonia and esterifying the dimethylsulphamyl anthranilic acid obtained. Other 5-sulphamylanthranilic methyl esters used as starting materials are similarly prepared via corresponding 5-sulphamyl-2-halo-benzoic acids, 2-Chloro-3-methyl-benzoic acid-5-sulphonyl chloride, used for the preparation of 3-methyl-5-dimethylsulphamyl-anthranilic methyl ester, is made by the action of chlorosulphonic acid on 2-chloro-3-methyl-benzoic acid. 5-Dimethylsulphamyl-2-chlorobenzoic acid hydrazide is made by esterifying 5-dimethylsulphamyl-2-chlorobenzoic acid and reacting the resulting ester with hydrazine hydrate. Pharmaceutical preparations active against Gram-positive and Gram-negative pathogens e.g. staphylococci and pneumococci, and mycobacteria, comprise the above sulphamyl anthranilic hydrazides of the invention or salts thereof with inorganic or organic acids, in admixture or conjunction with an inorganic or organic, solid or liquid carrier. The preparations suitably may take the form of tablets, dragees, capsules, suspensions solutions or emulsions which may contain preserving, stabilizing, wetting or emulsifying agents, salts for regulating osmotic pressure or buffers. The compounds may also be incorporated in animal fodder or in additives for animal fodder, for verterinary use.