Design, Synthesis, Antineoplastic Activity, and Chemical Properties of Bis(carbamate) Derivatives of 4,5-Bis(hydroxymethyl)imidazole

Article abstract of DOI:10.1021/jm00121a023

A series of bis(carbamate) derivatives of 1,2-substituted 4,5-bis(hydroxymethyl)imidazoles were prepared and evaluated against murine P388 lymphocytic leukemia.Electron-withdrawing substituents at either N-1 or C-2 gave rise to inactive compounds.However, electron-donating substituents gave active compounds and the 2-(methylthio)-1-methyl derivative 2i (carmethizole), as the bis(N-methylcarbamate), was found to be very active.The derivative 2i, referred to by the name carmethizole, was also shown to be active against the MX-1 mammary xenograft, the human amelanotic melanoma cell line (LOX) xenograft, the M5076 sarcoma, and L1210 lymphocytic leukemia.The solution stability, water solubility, pKa, and log P of carmethizole are also reported.