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Synthesis of retinoid X receptor-specific ligands that are potent inducers of adipogenesis in 3T3-L1 cells.

Abstract：

: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.

journal_name

J Med Chem

journal_title

Journal of medicinal chemistry

authors

Canan Koch SS,Dardashti LJ,Cesario RM,Croston GE,Boehm MF,Heyman RA,Nadzan AM

doi

10.1021/jm980621r

keywords:

subject

Has Abstract

pub_date

1999-02-25 00:00:00

pages

742-50

issue

4

eissn

0022-2623

issn

1520-4804

pii

jm980621r

journal_volume

42

pub_type

杂志文章

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