Synthesis and biological evaluation of chromone carboxamides as calpain inhibitors

[Display omitted] Excessive calpain activations contribute to serious cellular damage and have been found in many pathological conditions. Novel chromone carboxamides derived from ketoamides were prepared and evaluated for μ-calpain inhibition. Among synthesized, compound 2i was the most potent calpain inhibitor with an IC 50 value of 0.24 ± 0.11 μM comparable to the activity of peptide aldehyde calpain inhibitor MDL 28,170. Furthermore, compound 2i showed higher selectivity for μ-calpain over two related cysteine proteases cathepsin B and cathepsin L, suggesting the chromone ring as a good scaffold for selective μ-calpain inhibitors.