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.