Synthesis and Tumor - inhibitory Properties of 2 - Methylthio - 4 - (

We have previously reported the anti-neoplastic properties of ~-methylthio-4-amino-5-hydroxymethylpyrimidine (methioprim) and of other related pyrimidines with modification of the 2alkylthio substituent (2). These compounds were initially chosen for study following the observations of Guthrie et a/. that collateral sensitivity for methioprim was demonstrable in amethopterin-resistant strains of B. subtilis and purine antagonist-resistant strains of E. coli (1). Synthetic modifications of the ~-methylthio4,5-disubstituted-pyrimidines were undertaken in an attempt to extend and improve the antineoplastic activity of this series of compounds. The present paper reports the preparation of compounds in which the 4-amino group of methioprim, or of the corresponding 5-carbethoxypyrimidine, was replaced by substituted-anilino groups. The :3:3 compounds here reported have been studied for inhibition of growth of transplanted rodent tumors. Two have been found to show considerable activity.