Purine analogues as amplifiers of phleomycin. II. Some s-Triazolo[4,3-a]pyridines, s-Triazolo[4,3- or 1,5-a]pyrimidines and s-Triazolo[3,4-b]benzothiazoles

Abstract

s-Triazolo[4,3-a]pyridine-3(2H)-thione (1b) undergoes S-alkylation to give derivatives such as 2-(s-triazolo[4,3-a]pyridin-2'-ylthio)acetamide (4c) which may be oxidized to the corresponding sulfoxide (4g) and sulfone (4h). Likewise, alkylation of 1-methyl-s-triazolo[4,3-a]pyridinium-3-thiolate (2b) yields 3-carbamoylmethylthio-1-methyl-s-triazolo[4,3-a]pyridinium chloride (3).    

Similar treatment of s-triazolo[4,3-a]pyrimidine-3(2H)-thione (1c) leads to 2-(s-triazolo[4,3-a]-pyrimidin-3'-ylthio)acetamide (4j) and analogues, all of which undergo Dimroth-like rearrangement to their respective [1,5-a]-isomers (5), (6b) and analogues. 2-(s-Triazolo[3,4-b]benzothiazol-3'-ylthio)acetamide (9b) was also prepared from the corresponding thione (8).    

Activities of the above compounds as amplifiers of phleomycin against E. coli are tabulated. The amide (4c) is highly active, non- toxic and resistant to metabolism.