Synthesis and protein kinase C inhibitory activities of balanol analogs with replacement of the perhydroazepine moiety.

Y S Lai, J S Mendoza, G E Jagdmann, D S Menaldino, C K Biggers, J M Heerding, J W Wilson, S E Hall, J B Jiang, W P Janzen, L M Ballas

Index: J. Med. Chem. 40(2) , 226-35, (1997)

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Abstract

Balanol is a potent protein kinase C (PKC) inhibitor that is structurally composed of a benzophenone diacid, a 4-hydroxybenzamide, and a perhydroazepine ring. A number of balanol analogs in which the perhydroazepine moiety is replaced have been synthesized and their biological activities evaluated against both PKC and cAMP-dependent kinase (PKA). The results suggested that the activity and the isozyme/kinase selectivity of these compounds are largely related to the conformation about this nonaromatic structural element of the molecules.