C5,C6-disubstituted 1H-indole-2-carboxamides:: Synthesis and cytotoxic activity in the human non-small lung cancer cell line NSCLC-N16-L16

A facile synthesis of the disubstituted 1H-indole-2-carboxamides (6a-h) is described. Readily available 4-benzyloxy-3-methoxybenzaldehyde is converted to the parent acid (12) by nucleophilic attack of the azido-ester (9) and cyclization of the propenoic methyl ester (10). The target compounds (6a-d) were obtained by amidation of (12) with the appropriate primary amine. The new 6-hydroxy analogs (6e-h) were prepared by benzyl deprotection of (6a-d). The cytotoxicity of the new molecules was evaluated in the human non-small lung cancer cell line NSCLC-N16-L16 in vitro. One compound (6d) showed satisfactory activity (IC50 = 13.9 mu M) worthy of further study. It is noteworthy that few agents are clinically effective against human non-small lung cancer, and thus there is a need for novel agents for use in this disease.