The synthesis, analysis, stability and biotransformation of N- (3-methylphenyl) -N'-cyanobenzamidine and analogues
Pfeifer, S.; Barnikow, G.; Schulz, M.; Kraft, R.; Fritsche, E.
Die Pharmazie 36(11): 757-763
1981
ISSN/ISBN: 0031-7144 PMID: 7323123 Document Number: 172955
The antivirally active N-(3-methylphenyl)-N'-cyanobenzamidine (1) and some of its analogues were synthetized by the reaction of the ethyl ester of N-cyanobenzimidic acid with the corresponding arylamines. The analytical profile of 1 and of some of its analogues, which is needed for stability and biotransformation studies, was established by means of the following techniques: solubility determination, TLC, UV, IR and MS. When 1 is heated with methanolic HCl and NaOH (0.5 mol/l) for 1 h, several hydrolysis products are formed: m-toluidine, benzoic acid, benzoic acid 3-toluidide, N-(3-methylphenyl)benzamidine, N-(3-methylphenyl)-N'-carboxamidobenzamidine, benzoylurea, However, 1 is fairly stable under physiological conditions so biotransformation studies are not affected. After oral application of 1 to rats, the 3-hydroxymethyl and the 3-methyl-5-hydroxy compound as well as its glucuronide and sulphate conjugate were detected in the urine. The faeces contained considerable amounts of unchanged 1 (incomplete absorption).