Protein kinase C inhibitory activities of balanol analogs bearing carboxylic acid replacements

A variety of balanol analogs bearing carboxylic acid replacements (amides, sulfonamides and tetrazoles) were synthesized and evaluated for protein kinase C (PKC) inhibitory activity. In general, those compounds which bear an acidic proton (pKa ≤ 7.6) display potent PKC activity, and show selectivity for PKC over other kinases. Prodrugs are excellent tools for increasing cellular activity of some acid replacements.