Purine studies. XIX. Rodential metabolism of 2-(6',8',9'-Trimethylpurin-2'-ylthio)propionamide and related purines

Abstract

The metabolic oxidation of three purines, which increase the antibiotic activity of phleomycin in vitro, has been investigated in mice. 2-(6',8',9'-Trimethylpurin-2'-ylthio)acetamide (lb) gave 46% unchanged amplifier and 26% of the corresponding sulphoxide (1c); the homologous propionamide (1f) gave only 20% unchanged material, 6% of the corresponding sulphoxide (1g), 30% of a highly unusual metabolite (1h) formed by hydroxylation of the 8'-methyl group, and two unidentified products; and 6,8,9-trimethyl-2-(piperidin-1'-yl)purine (1k) gave but 4% unchanged material, a little 6,8,9-trimethylpurin-2-one, and c. 45% of an intractable product. 2-(6',9'-Dimethylpurin-2'-y1thio)acetamide (la) was appreciably less metabolized to its 8-oxo derivative (2; R = SCH₂CONH₂) in rats than in mice. Unambiguous syntheses for radioactively labelled amplifiers, metabolites and potential metabolites are described.