9-cis-Retinoic acid analogues with bulky hydrophobic rings:: new RXR-selective agonists

被引：14

作者：

Alvarez, R

Vega, MJ

Kammerer, S

Rossin, A

Germain, P

Gronemeyer, H

de Lera, AR ^{[1
]}

机构：

[1] Univ Vigo, Fac Quim, Dept Quim Organ, Vigo 36200, Spain

[2] Inst Genet & Biol Mol & Cellulaire, Dept Cell Biol & Signal Transduct, F-67404 Illkirch Graffenstaden, France

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2004年 / 14卷 / 24期

关键词：

9-cis-Retinoic acid; RXR agonist; nuclear receptor;

D O I：

10.1016/j.bmcl.2004.08.072

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Stille cross-coupling of aryltriflates 10 and dienylstannane 11, oxidation and Horner-Wadsworth-Emmons reaction afforded stereoselectively retinoates 15. Saponification provided the carboxylic acids 8a and 86, retinoids that incorporate a bulky hydrophobic ring while preserving the 9-cis-geometry of the parent system. In contrast to the pan-RAR/RXR agonistic profile of the lower homologue of 8a, compound 7 (LG100567), retinoids 8 showed selective binding and transactivation of RXR, devoid of significant RAR activation. In PLB985 leukemia cells that require RXR agonists for differentiation compounds 8 induced maturation in the presence of the RAR-selective pan-agonist TTNPB; this effect was blocked by an RXR-selective antagonist. (C) 2004 Elsevier Ltd. All rights reserved.

引用

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页码：6117 / 6122

页数：6

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