Inhibitory activity and selectivity of staurosporine derivatives towards protein kinase C

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Abstract

The synthesis and in vitro protein kinase C (PKC) inhibition of a series of staurosporine derivatives is described. Essential for activity is a free NH of the lactam portion of the molecule. A large variety of substituents is tolerated at the secondary amine, although in most cases these modifications lead to a decrease in activity. Acylation of the methylamino group leads generally to the most selective derivatives with respect to other serine/threonine and tyrosine kinases.

The inhibition of various serine/threonine- and tyrosine-specific protein kinases by a series of staurosporine derivatives is presented.

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