Studies on Chemotherapeutic Agents against Mycobacterium Tuberculosis. XXVII. Synthesis and Antituberculous Activity of 1-Alkyl-3-(3'-hydroxy-4'-alkoxycarbonylphenyl)-2-thiourea and 1-Aryl-3-(3'-hydroxy-4'-alkoxycarbonylphenyl)-2-thiourea

A total of 180 compounds, 54 kinds of 1-alkyl-3-(4'-alkoxycarbonyl-3'-hydroxyphenyl)-2-thiourea and 126 kinds of 1-aryl-3-(4'-alkoxycarbonyl-3'-hydroxyphenyl)-2-thiourea, were synthesized and their antibacterial activity was tested against human-type tubercle bacilli H37Rv strain. 1) None of the 1-alkyl derivatives showed stronger antibacterial activity than p-amino-salicylic acid (PAS) and 1, 3-di-(p-iso-pentoxyphenyl)-2-thiourea (DAT). 2) Among the 1-aryl derivatives, 1-(p-butoxyphenyl)-3-(3'-hydroxy-4'-isobutoxycarbonylphenyl)-2-thiourea and 1-(p-pentoxyphenyl)-3-(4'-ethoxycarbonyl-3'-hydroxyphenyl)-2-thiourea inhibited the growth of the bacillus in a concentration of 0.39 μg/ml, indicating antibacterial activity comparable to PAS or stronger than DAT. In addition, 1-(p-propoxyphenyl)-3-(3'-hydroxy-4'-methoxycarbonylphenyl), 1-(p-propoxyphenyl)-3-(4'-ethoxycarbonyl-3'-hydroxyphenyl), 1-(p-propoxyphenyl)-3-(3'-hydroxy-4'-propoxycarbonylphenyl), 1-(p-propoxyphenyl)-3-(4'-butoxycarbonyl-3'-hydroxyphenyl), 1-(p-propoxyphenyl)-3-(3'-hydroxy-4'-isobutoxycarbonylphenyl), 1-(p-butoxyphenyl)-3-(4'-butoxycarbonyl-3'-hydroxyphenyl), and 1-(p-pentoxyphenyl)-3-(3'-hydroxy-4'-propoxycarbonylphenyl) derivatives inhibited bacillary growth in a concentration of 0.78 μg/ml, a comparable effect as that of DAT. 3) Result of experiments on a part of 1-alkyl derivatives showed that some of these compounds had no cross resistance with PAS and had stronger antibacterial activity against resistant strains rather than sensitive strains.