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.
RHeoGene, PO Box 949, 727 Norristown Road, Spring House, PA 19477-0949, USA. ctice@concurrentpharma.com
Colin M
CM
Tice
Robert E
RE
Hormann
Christine S
CS
Thompson
Jennifer L
JL
Friz
Caitlin K
CK
Cavanaugh
Jessica A
JA
Saggers
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