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

• Published in: Bioorganic & medicinal chemistry letters Vol. 13; no. 11; pp. 1883 - 1886
• Main Authors: Tice, Colin M., Hormann, Robert E., Thompson, Christine S., Friz, Jennifer L., Cavanaugh, Caitlin K., Saggers, Jessica A.
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 02.06.2003; Elsevier
• Subjects: Animals; beta-Galactosidase - biosynthesis; beta-Galactosidase - genetics; Biological and medical sciences; Bombyx; Chemical control; CHO Cells; Control; Cricetinae; Ecdysone - agonists; Fundamental and applied biological sciences. Psychology; Gene Expression Regulation - drug effects; Genes, Reporter; Ketones - chemical synthesis; Ketones - chemistry; Ketones - pharmacology; Lepidoptera; Molecular Structure; Phytopathology. Animal pests. Plant and forest protection; Protozoa. Invertebrates; Receptors, Steroid - biosynthesis; Receptors, Steroid - genetics; Receptors, Steroid - metabolism; Transcriptional Activation - drug effects; Agonist; Cyclohexane derivatives; Insecticide; Insecta; Bombyx mori; Oxygen heterocycle; Reporter gene; Choristoneura fumiferana; Ecdysteroide; Bicyclic compound; Aromatic compound; Ecdysone; Chemical synthesis; Non steroid compound; Pesticides; Insect growth regulator; Gene expression; Ketone; Response element; Biological activity; Tortricidae; Arthropoda; Bombycidae; Lepidoptera; Carboxamide; Invertebrata
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/S0960-894X(03)00315-9

Fifteen new α-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 α-acylaminoketone was identified which had activity equal to that of the standard dibenzoylhydrazine ecdysone agonist GS ™-E in the assay based on CfEcR. Graphic