Synthesis of Retinoid X Receptor-Specific Ligands That Are Potent Inducers of Adipogenesis in 3T3-L1 Cells

Autor: Alex M. Nadzan, Marcus F. Boehm, Cesario Rm, Dardashti Laura J, Canan Koch Ss, Richard A. Heyman, Glenn Croston
Rok vydání: 1999
Předmět:
Zdroj: Journal of Medicinal Chemistry. 42:742-750
ISSN: 1520-4804
0022-2623
DOI: 10.1021/jm980621r
Popis: A novel series of oxime ligands has been synthesized that displays potent, specific activation of the retinoid X receptors (RXRs). The oximes of 3-substituted (tetramethyltetrahydronaphthyl)carbonylbenzoic acids are readily available by condensation with hydroxyl- or methoxylamine; alkylation of the hydroxyl oxime provides a variety of analogues. Oximes and variously substituted oxime derivatives demonstrate high binding affinity for the RXRs and specific RXR activation and, hence, are called rexinoids. These oxime rexinoids are activators of the RXR:PPARgamma heterodimer and are potent inducers of differentiation of 3T3-L1 preadipocytes to adipocytes. We have recently reported that ligands which activate the RXR:PPARgamma heterodimer in this manner are effective in the treatment of type II diabetes (non-insulin-dependent diabetes mellitus, NIDDM). Thus, these new oxime rexinoids are potential therapeutic agents for the treatment of metabolic disorders, such as obesity and diabetes.
Databáze: OpenAIRE