Synthesis and Evaluation of Furan, Thiophene, and Azole Bis[(carbamoyloxy)methyl] Derivatives as Potential Antineoplastic Agents¹

A series of bis(hydroxymethyl)-substituted heterocycles were synthesized and converted to the corresponding bis(methylcarbamate) derivatives. The heterocyclic systems studied were based on 2-phenyl-3-methylfuran (2-4), 1-phenylpyrazole (5-7), l-phenyl-5-methylpyrazole (9-11), l-phenyl-5-methylthiophene (13), 1-phenyl-l,2,3-triazole (14), 3-phenylisoxazole (15), 3-phenylisothiazole (16), 2-phenylthiazole (17), and 2-phenyloxazole (18). None of the bis (carbamates) prepared was active against murine P388lymphocytic leukemia. Pyrrole bis (carbamates) 20 and 21, which exhibited antileukemicactivity, also showed reactivity toward 4-(p-nitrobenzyl)pyridine while the inactive bis(carbamates) were unreactive in the 4-(p-nitrobenzyl)pyridine assay.