Purine Analogues as Amplifiers of Phleomycin. VI. The Synthesis and Metabolism of Some Benzothiazole, Benzoxazole and s-Triazolopyrimidine Amplifiers

Abstract

The metabolisms of four 14C-tagged amplifiers of phleomycin are followed in mice. 2-(Benzothiazol- 2'-ylthio)acetamide (1c) gives mainly the corresponding acid (1e) in the urine; 2-(benzoxazol-2'- ylthio)acetamide (1d) likewise gives the acid (1f); N-methyl-2-(s-triazolo[4,3-a]pyrimidin- 3'-ylthio)propionamide (2b) gives unchanged material (c. 20%) plus not the corresponding acid (2c), but its [1,5-a] isomer (3c) in 60% yield; and 2-(5',7'-diethyl-s-triazolo[4,3- a]pyrimidin-3'-ylthio)-acetamide (2i) proves much more stable by giving mainly unchanged material (>60%). Minor metabolites are formed in each case. ��� Syntheses and N.M.R. spectra of the above substrates and related derivatives are reported as well as their activities as amplifiers of phleomycin against in vitro cultures of Escherichia coli.