Design, synthesis and evaluation of retinoids with novel bulky hydrophobic partial structures

被引：13

作者：

Amano, Yohei ^{[1
]}

Noguchi, Masayuki ^{[1
]}

Nakagomi, Madoka ^{[1
]}

Muratake, Hideaki ^{[1
]}

Fukasawa, Hiroshi ^{[1
]}

Shudo, Koichi ^{[1
]}

机构：

[1] Res Fdn Itsuu Lab, Setagaya Ku, Tokyo 1580094, Japan

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2013年 / 21卷 / 14期

关键词：

Retinoid; RAR; Agonist; Bulky hydrophobic fragment; Amide; PROMYELOCYTIC LEUKEMIA-CELLS; DIFFERENT NUCLEAR RECEPTORS; UNION-OF-PHARMACOLOGY; ACID RECEPTOR; RETINOBENZOIC ACIDS; ALZHEIMERS-DISEASE; X-RECEPTORS; ALPHA; MOUSE; GAMMA;

D O I：

10.1016/j.bmc.2013.04.053

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Many synthetic retinoids contain an aromatic structure with a bulky hydrophobic fragment. In order to obtain retinoids with therapeutic potential that do not bind to or activate retinoic acid X receptors (RXRs), we focused on the introduction of novel hydrophobic moieties, that is, metacyclophane, phenalene and benzoheptalene derivatives. The designed compounds were synthesized and their agonistic activities towards RARs and RXRs were evaluated. Most of the active compounds showed selectivity for RAR alpha and RAR beta over RAR gamma, and higher RAR beta transactivating activity seemed to correlate with higher cell differentiation-inducing activity towards promyelocytic leukemia cell line HL-60. These compounds showed no agonistic activity towards RXRs. (C) 2013 Elsevier Ltd. All rights reserved.

引用

页码：4342 / 4350

页数：9

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