CHEMOTHERAPEUTIC STUDIES OF SCHISTOSOMIASIS——ⅪⅤ.SYNTHESIS OF SOME HALOGEN SUBSTITUTED DIPHENYL SULPHIDES AND SULPHOXIDES AND SOME MANNICH BASES DERIVED FROM DIPHENYL SULPHIDES

In view of the cffectivcness of bis(3,5,6-trichloro-2-hydroxyphenyl)-sulphide (I_b, CMS-390) and bis(3-bromo-5-chloro-2-hydroxyphenyl)_sulphide(I_a, CMS-349) in the treatment of schistosomiasis japonicum, a series of analogous compounds was prepared in the present work for pharmacological examinations. The compounds I₂ and I_b were oxidized with hydrogen peroxide, forming the corresponding sulphoxides (II₂ and II_b). The compound substituted with mixed halogens (I_c) was prepared by bromination of the corresponding chloro-compound. When phenols with various substituents were reacted with sulphur chloride, the corresponding diphenyl sulphides were obtained. The Mannich bases were obtained by heating 2,2'-dihydroxydiphenyl sulphides with formaldehyde and secondary amines. The piperazine salts were prepared by coupling the corresponding diphenyl sulphides with anhydrous piperazine. Preliminary pharmacological examinations showed that bis (3-bromo-4,5-dichloro-2-hydroxyphenyl)-sulphide (I_c), bis (3-bromo-5-chloro- 2-hydroxyphenyl)-sulphoxide (II₂), bis (3,5,6-trichloro-2-hydroxyphenyl)-sulphoxide (II_b) and the piperazine salt of bis(3-bromo-5-chloro-2-hydroxyphenyl-sulphide and bis(3,5,6- trichloro-2-hydroxyphenyl)-sulphde were quite effective against Schistosoma japonicum.