Synthesis of Lipophilic-2-Mercaptobenzoxazoles and 2-Spirothiophene-Phosphonate Derivatives as Potent Anticancer Agents

As a part of our ongoing research program in developing new anticancer agents, herein, we report the synthesis of a series of 2-mercapto-2,3-dihydrobenzoxazole-2-methyl-, -2-thioethyl-, and/or 2-spirothiophene-phosphonates. Five of these new compounds that combine three bioactive moieties: oxazole, thiol, and phosphonate motifs, exhibited remarkable growth inhibition against 13 carcinoma cell lines. The results of the experimentally determined log K and clog P values are in agreement with Lipinski Rule >5 and showed a strong correlation with the pharmacological results; nevertheless, it is poorly consisted with calculated log P/Clog P and log P/ACD.