SYTHESIS AND ANTISCHISTOSOMAL ACTION OF PHENITHIONATE AND RELATED DERIVATIVES OF THIOCARBAMIC ACID

Twenty-two derivatives of thiocarbamic acid relating to 4-nitro-4'-thiocyanatodiphenylamine (Nithiocyamine C9333-GO/CG 4540) were synthesized. They were 4-nitrodiphenylamine-4'-thiocarbamide Ⅰ, alkyl 4'-thioncarbamate Ⅱ, alkyl 4'-dithiocarbamate Ⅲ, aryl 4'-thioncarbamate Ⅳ, aryl 4-nitrodiphenylether-4'-thioncarbamate Ⅴ and its diphenyl-thioether analogue Ⅵ. Screening data showed that Ⅲ, Ⅳ and Ⅴ sustained the pronounced activity as possessed by nithiocyamine against Schistosomiasis japonca on mice, while Ⅰ, Ⅱ and Ⅵ showed no appreciable activity. Preliminary clinical observations demonstrated that phenyl-4-nitrodiphenylamine-4'-thioncarbamate——phenithionate was as effective as nithiocyamine but less toxic. Detailed results will be reported elsewhere. Structure-activity relationship was briefly discussed.