CHEMOTHERAPEUTIC STUDIES ON SCHISTOSOMIASIS——ⅩⅢ.SYNTHESIS OF SOME HALOGEN-SUBSTITUTED DIPHENYL SULPHIDES

In view of the effectiveness of bis(3,5-dichloro-2-hydroxyphenyl) sulphide (Bithionol, Ⅱ_b) in the treatment of human paragonimiasis and its protective action against the cercariae of Schistosoma mansoni, a series of analogous compounds was prepared in the present work for pharmacological examinations. 2,2'-Dihydroxy-5,5'-diphenyl sulphide (Ⅱ_a) was chlorinated by means of tert-butyl hypochlorite, or brominated by means of either bromine or N-bromosuccinimide, giving mono- or di-substituted derivatives. The compounds substituted with mixed halogens were prepared by bromination of the corresponding chloro-componnds. Many of such phenolic compounds were also acetylated, benzoylated or etherified, and compounds carrying various side chains of acyloxy, alkoxy or 2-diethylamino-ethoxy linkages were afforded. Since these compounds have a wide range of physico-chemical properties, it is expected that their pharmacodynamic properties would also be different. Preliminary pharmacological examinations revealed that bis (3,5,6-trichloro-2-hydroxyphenyl) sulphide (Ⅳ_a) was quite active against Schistosoma japonicum, and bis(3-bromo-5-chloro-2-hydroxyphenyl) sulphide (Ⅱ_c) was less active.