Patent GB-1004974-A (GB)
Title: New amidines, process for their preparation and pharmaceutical compositions containing them
IPC: C07D207/34
Filed: 1964-03-31
Abstract: The invention comprises compounds of formula <FORM:1004974/C2/1> and their acid addition salts, wherein A is a straight or branched chain alkylene radical having 1 to 5 carbon atoms, R is an alkyl group having up to 4 carbon atoms and R1 is a carbamoyl, mono- or di-alkyl carbamoyl wherein the alkyl groups have up to 4 carbon atoms, alkoxy carbonyl, aralkoxycarbonyl or carboxylic acyl group, acyl groups specified being aliphatic acyl amidino-acyl, benzoyl, or pyridylcarbonyl groups, or a group of formula Z-X-CO, where X is a p-phenylene, chloro-p-phenylene, furylene or 1-methyl-pyrrelene radical and Z is a nitro, amino, formamido, acetamido, ureido, amidino, guanidino, amidinoacetamido, guanidinoacetamido, 3-guanidinopropionamido- or 4-guanidinobutyramido group, and their preparation by (a) reacting a compound of formula <FORM:1004974/C2/2> wherein R1 may, in addition to the above definition, contain a cyano-substituent, with hydrogen chloride in the presence of an alkanol having up to 6 carbon atoms to form a compound of formula <FORM:1004974/C2/3> wherein any cyano-group in R1 is similarly converted and R11 is an alkyl group having up to 6 carbon atoms, and reacting this product with ammonia, (b) acylating compounds wherein R1 is a hydrogen atom, (c) hydrogenating a nitro-product to an amino-product, (d) reacting an amino-product with potassium cyanate to give a ureido-product, with cyanamide to give a guanidino-product, or with a guanidino carboxylic acid to give a guanidinoacylamino-product, or (e) reacting an amino-product with an N-benzyloxycarbonyl amino-acid, to obtain the corresponding amide, removing the protecting group, and reacting the free amino group with S-methyl isothiouronium bromide to convert it to a guanidino-group. Compounds of formula <FORM:1004974/C2/4> are prepared by acylation or, if R1 is to be a carbamoyl group, by reacting the free amino-compound with potassium cyanate. Compounds of the first general formula wherein R1 is a hydrogen atom are prepared by treating a 4 - nitro - 2 - (g  - cyano - alkylcarbamoyl) - pyrrole as in process (a) above, and hydrogenating the 4-nitro-product. 4 - Amino - 2 - (g  - cyano - alkylcarbamoyl)-pyrrols are prepared by reacting a 4-nitro-pyrrole-2-carboxylic acid halide, formed by reacting the acid with thionyl chloride, with the appropriate cyanoamine and hydrogenating the nitro-product after, if desired, introducing a 1-butyl group by reaction with butyl iodide. 1 - Methyl - 4 - nitro -pyrrole - 2 - carboxylic acid is prepared by treating the corresponding 2-cyano-pyrrole with hydrogen chloride in ethanol to give an imino-ether as in process (a) above, hydrolysing this product to give the 2-carboxylic acid ethyl ester, and saponifying this product to give the free acid. 4-Benzyloxycarbonylamino-butyric acid is prepared by reaction of benzyl chloroformate and 4-amino-butyric acid. The compounds of the invention have anti-tubercular and virucidal activity, and may be used in the form of their non-toxic acid addition salts in combination with a pharmaceutical carrier in forms suitable for oral, parenteral or rectal administration, e.g. as capsules, compressed tablets, pills, powders, granules, solutions, suspensions, emulsions, syrups, elixirs and suppositories.