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Syntheses and structure-activity relationships of novel retinoid X receptor agonists.

Abstract：

:As part of our studies to develop novel retinoids with increased affinity and selectivity for the retinoid X receptor (RXR) subfamily, we have designed and synthesized a series of (E,E,E)-7-(1,2,3, 4-tetrahydroquinolin-6-yl)-7-alkyl-6-fluoro-3-methylhepta-2, 4, 6-trienoic acid derivatives. These tetrahydroquinolines, generated by introducing a polar N atom into the hydrophobic part of the retinoid skeleton, showed high binding affinity to RXRs. Addition of fluorine at the 6-position of the 2,4,6-trienoic acid moiety afforded compounds which elicit potent and selective transactivation of the RXRs. Compound 14b (ER-35794), which possesses an ethyl substituent at the 7-position and fluorine at the 6-position of the triene moiety, is one of the most potent and selective RXR agonists reported to date.

journal_name

J Med Chem

journal_title

Journal of medicinal chemistry

authors

Hibi S,Kikuchi K,Yoshimura H,Nagai M,Tai K,Hida T

doi

10.1021/jm980058c

subject

Has Abstract

pub_date

1998-08-13 00:00:00

pages

3245-52

issue

17

eissn

0022-2623

issn

1520-4804

pii

jm980058c

journal_volume

41

pub_type

杂志文章

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