Computer-Assisted Structure–Anticancer Activity Correlations of Carbamates and Thiocarbamates

With the aid of the computer, ∼8000 compounds that incorporate a carbamate or thiocarbamate moiety, which have been tested as potential anticancer agents at the National Cancer Institute (NCI), were classified and their structure–activity correlations against the in vivo P-388 and L-1210 leukemias were evaluated. Aromatic carbamates and thiocarbamates have shown good activity against P-388 and poor activity against L-1210. The majority of active compounds in this series of aromatic carbamates possess a 2- or 4-heteroatom-substituted phenyl attached to the carbamate oxygen atom or the thiocarbamate sulfur atom with the carbamate nitrogen atom as NHMe. The N-phenyl carbamates were much less active against P-388 than the phenyl carbamates; only bis-N-phenyl carbamates with a methylene bridge between the two phenyl groups showed good activity against both P-388 and L-1210 leukemias. Except for the mycophenolic acid carbamates, the fused phenyl carbamates showed poor activity against both P-388 and L-1210 leukemias. Certain nitrogen–heterocyclic carbamates and carbamates with heteroatom substituents have been selected by the NCl for development toward clinical trials. The nature of the heterocyclic carrier and the position of attachment to the carbamate moiety have a major role on the mode of action of the antitumor activity of these compounds.