Synthesis, computer modeling and biological evaluation of novel protein kinase C agonists based on a 7-membered lactam moiety

Y Endo, M Shimazu, H Fukasawa, PE Driedger…

Index: Endo, Yasuyuki; Shimazu, Masako; Fukasawa, Hiroshi; Driedger, Paul E.; Kimura, Kaname; Tomioka, Nobuo; Itai, Akiko; Shudo, Koichi Bioorganic and Medicinal Chemistry Letters, 1999 , vol. 9, # 2 p. 173 - 178

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Citation Number: 8

Abstract

4-Hydroxymethyl-5a-methyl-1, 3, 4, 5, 5aβ, 6, 7, 8, 9, 9aα-decahydro-2H-benz [d] azepin-2- ones (4–12), which were designed to mimic the biologically active conformation of teleocidins and benzolactams, were synthesized and evaluated for the ability to compete with [3H] phorbol 12, 13-dibutyrate in a PKCδ binding assay. Among the compounds, 10–12 showed potent binding affinity, with inhibition constants (Ki) of low nanomolar order. ...