Syntheses And Antimicrobial Activities of N-heterocyclic-β-mercaptocinnamamides And Related Compounds

Abstract

In order to obtain useful antimicrobial compounds, a number of N-heterocyclic-β-mercaptocinnamamides (Ilia—i) and related compounds were prepared. N-Heterocyclic phenylpropiolamides (I) were obtained by the reaction of heterocyclic amines with phenyl-propioloyl chloride. The addition of thiourea to I gave the isothiuronium salts (II), which were converted into the mercapto compounds (III) with aqueous sodium hydroxide. In the reaction of 2-aminothiazole or 2-amino-4-methylthiazole with phenylpropioloyl chloride in the presence of triethylamine, thiazolo[3,2-a]pyrimidines (V, VII and VIII) were given together with the expected amides (If and Ig). The hydrolysis of S-[2-(3-methyl-1 -phenyl-5-pyrazolyl)carbamoyl- 1-phenylvinyl]-isothiourea p-toluenesulfonate (He) with aqueous sodium hydroxide at 90° gave 6,7-dihydroe l,4-diphenyl-3-methyl-6-oxopyrazolo[3,4-b]pyridine (IX) and a small amount of the mercapto compound (Me). Acyl migration from S to N was found in the acylthio derivatives of N-(2-thiazolyl)-(IHf) and N-(4-methyl-2-thiazoly1)-β-mercaptocinnamamide (IIIg). Most of the compounds synthesized were considerably active in vitro against various gram-positive bacteria and fungi. However, only three of them were effective against Trichophyton in the in vivo tests. © 1972, The Pharmaceutical Society of Japan. All rights reserved.