[Synthesis of antiproteolytically active 3,5-bis(4-amidinobenzyl)- and 3,5-bis(4-amidinobenzylidene)piperidone-(4) derivatives (author's transl)].

Because of the good inhibitory effects of some alpha, alpha'-bis (amidinobenzylidene)cycloalkanoes and of their hydrogenation products on serine proteinases, the authors prepared structurally analogous bisamidines of heterocycloalkanones. To obtain 3,5-bis(4-amidinobenzyl)-N-benzoylpiperidone-(4), N-benzoylpiperidone-(4) was condensed with 4-cyanobenzaldehyde in concentrated phosphoric acid. The resultant 3,5-bis(4-cyanobenzylidene)-N-benzoylpiperidone-(4) was reduced with zinc-glacial acetic acid, and the reduction product was converted into the respective bisamidine by means of the Pinner method. 3-(4-Cyanobenzylidene)-5-(4-aminocarbonylbenzylidene)-N-benzoylpiperidone-(4) was isolated as a by-product of the condensation of N-benzoylpiperidone-(4) with 4-cyanobenzaldehyde. To prepare 3,5-bis(4-amidinobenzylidene)-N-benzoylpiperidone-(4), N-benzoylpiperidone-(4) was condensed with 4-amidinobenzaldehyde hydrochloride in concentrated phosphoric acid. The resultant bis-dihydrogen phosphate was converted into the bis-hydrochloride by treatment with methanolic hydrochloric acid solution in the cold, and debenzoylated to 3,5-bis(4-amidinobenzylidene)piperidone-(4) trihydrochloride on heating with methanolic hydrochloric acid solution.