Synthesis and evaluation of furan, thiophene, and azole bis[(carbamoyloxy)methyl] derivatives as potential antineoplastic agents.
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), 1-phenyl-5-methylpyrazole (9-11), 1-phenyl-5-methylthiophene (13), 1-phenyl-1,2,3-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 P388 lymphocytic leukemia. Pyrrole bis(carbamates) 20 and 21, which exhibited antileukemic activity, also showed reactivity toward 4-(p-nitrobenzyl)pyridine while the inactive bis(carbamates) were unreactive in the 4-(p-nitrobenzyl)pyridine assay.
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis*; D002219:Carbamates / Q000138:chemical synthesis* / Q000633:toxicity; D055598:Chemical Phenomena; D002621:Chemistry; D004353:Drug Evaluation, Preclinical; D005663:Furans / Q000138:chemical synthesis* / Q000633:toxicity; D007202:Indicators and Reagents; D007941:Leukemia P388 / Q000473:pathology; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D011758:Pyrroles / Q000138:chemical synthesis* / Q000633:toxicity; D013053:Spectrophotometry; D013329:Structure-Activity Relationship; D013876:Thiophenes / Q000138:chemical synthesis* / Q000633:toxicity
D000970:Antineoplastic Agents; D002219:Carbamates; D005663:Furans; D007202:Indicators and Reagents; D011758:Pyrroles; D013876:Thiophenes