Optimization of alpha-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 dibenzoylhydrazine ecdysone agonist GS()-E in the assay based on CfEcR.
Tice
Colin M
CM
RHeoGene, PO Box 949, 727 Norristown Road, Spring House, PA 19477-0949, USA. ctice@concurrentpharma.com
Hormann
Robert E
RE
Thompson
Christine S
CS
Friz
Jennifer L
JL
Cavanaugh
Caitlin K
CK
Saggers
Jessica A
JA
D000818:Animals; D012831:Bombyx; D016466:CHO Cells; D006224:Cricetinae; D004440:Ecdysone / Q000819:agonists*; D005786:Gene Expression Regulation / Q000187:drug effects*; D017930:Genes, Reporter; D007659:Ketones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D007915:Lepidoptera; D015394:Molecular Structure; D011987:Receptors, Steroid / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D015533:Transcriptional Activation / Q000187:drug effects; D001616:beta-Galactosidase / Q000096:biosynthesis / Q000235:genetics
D007659:Ketones; D011987:Receptors, Steroid; C055469:ecdysone receptor; D004440:Ecdysone; D001616:beta-Galactosidase