Synthesis and SAR of alpha-acylaminoketone ligands for control of gene expression.
A lead discovery library and a follow-up focused library of alpha-acylaminoketones were designed based on known dibenzoylhydrazine ecdysone agonists, including GS(TM)-E. The compounds were assayed in mammalian cells expressing the ecdysone receptor from Bombyx mori for their ability to cause expression of a reporter gene downstream of an ecdysone response element. The most potent alpha-acylaminoketones were comparable to GS(TM)-E in this assay.
Tice
Colin M
CM
RHeoGene, PO Box 949, 727Norristown Road, Spring House, PA 19477-0949, USA. ctice@rheogene.com
Hormann
Robert E
RE
Thompson
Christine S
CS
Friz
Jennifer L
JL
Cavanaugh
Caitlin K
CK
Michelotti
Enrique L
EL
Garcia
Javier
J
Nicolas
Ernesto
E
Albericio
Fernando
F
D000588:Amines / Q000138:chemical synthesis* / Q000494:pharmacology*; D000818:Animals; D012831:Bombyx / Q000378:metabolism; D002478:Cells, Cultured; D004440:Ecdysone / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects*; D007202:Indicators and Reagents; D007659:Ketones / Q000138:chemical synthesis* / Q000494:pharmacology*; D007928:Lethal Dose 50; D051379:Mice; D008968:Molecular Conformation; D011987:Receptors, Steroid / Q000037:antagonists & inhibitors; D013329:Structure-Activity Relationship; D001616:beta-Galactosidase / Q000096:biosynthesis / Q000235:genetics
D000588:Amines; D007202:Indicators and Reagents; D007659:Ketones; D011987:Receptors, Steroid; C055469:ecdysone receptor; D004440:Ecdysone; D001616:beta-Galactosidase