NOVEL HYDRAZINE DERIVATIVES AND A PROCESS FOR THE MANUFACTURE THEREOF

摘要

The invention comprises compounds of the formula X-CH2-NH-NHCH3 and acid (including ascorbic acid) addition salts thereof, wherein X represents a mononuclear or polynuclear oxygen-, nitrogen- and/or sulphur containing heterocyclic residue which may contain one or more alkyl, trifluoromethyl, cyano, mercapto alkylthio, amino, acylamino, ureido, alkylsulphonylamino, guanidino, amidino, aminoalkyl, carbamoyl, allophanoyl, sulphamoyl, nitro, 2-methylhydrazinomethyl, acyl and phenyl groups or halogen atoms, the preparation thereof by either reacting methylhydrazine, or a methylhydrazine in which hydrazine group is partially substituted by protecting groups such as acyl, alkoxycarbonyl, benzyloxycarbonyl, or benzyl, with an agent which yields the moiety X1-CH2-, wherein X1 has the meaning as X or is convertible into X, or methylating a hydrazine which contains such a moiety as a substituent, or such a substituted hydrazine which is partially further substituted by protecting groups such as acyl, alkoxycarbonyl, benzyloxycarbonyl or benzyl, and, in either case if necessary converting the moiety X1 in the product into X and, also if necessary, splitting off any protecting groups present and, if desired, converting the base into its acid addition salt. In a variation the agent in the above process may be substituted for an appropriate aldehyde and the resulting hydrazone catalytically hydrogenated. In a further variation 1,2-di(alkoxycarbonyl) - hydrazine is methylated and then reacted with the agent which yields the residue X1-CH2- and the alkoxycarbonyl groups split off from the products. The conversion of X1 to X may be effected at any point. Carbamoyl compounds may be prepared from the carboxylic acids either by direct condensation or through the acid halide or anhydride, or from the nitriles; acylamino compounds from the amines derived in turn by reduction of nitro or azo compounds, ureido compounds from cyanates and isocyanates; guanidino compounds from cyanamides and amidino compounds from the nitriles through the imido ethers or imido halides. 5 - [(2 - Methyl - 1,2 - di(benzyloxycarbonyl)-hydrazino) - methyl] thiophene - (2) - carboxylic acid chloride was prepared from the free acid, in turn prepared from the methyl ester, in turn prepared from 1-methyl-1,2-di(benzyloxycarbonyl) - hydrazine and 5 - (chloro - methyl)-thiophene - (2) - carboxylic acid methyl ester. The above acid chloride was also converted into the acyl isothiocyanate. Pharmaceutical compositions comprise the compounds of the invention and an inert carrier and may be in the form of tablets, dragees, suppositories, capsules, suspensions or emulsions. The compounds are cystostatic agents.