Optimization of α-acylaminoketone ecdysone agonists for control of gene expression

Fifteen new alpha-acylaminoketones were prepared by four different routes in an initial effort to optimize the potency of these compounds as ecdysone agonists. The compounds were assayed in mammalian cells expressing the ecdysone receptors from Bombyx mori (BmEcR) and Choristoneura fumiferana (CfEcR) for their ability to cause expression of a reporter gene downstream of an ecdysone response element. A new alpha-acylaminoketone was identified which had activity equal to that of the standard diben-zoylhydrazine ecdysone agonist GS(TM)-E in the assay based on CfEcR. (C) 2003 Elsevier Science Ltd. All rights reserved.