Design, synthesis, and structure-activity relationship studies of novel 6,7-locked-[7-(2-alkoxy-3,5-dialkylbenzene)-3-methylocta]-2,4,6-trienoic acids
Design, synthesis, and structure-activity relationship studies of novel 6,7-locked-[7-(2-alkoxy-3,5-dialkylbenzene)-3-methylocta]-2,4,6-trienoic acids
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DOI：
10.1021/jm020401k
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发表时间：
2003-09-11
影响因子：
7.3
通讯作者：
Boehm, MF
中科院分区：
文献类型：
--
作者：
Michellys, PY;Ardecky, RJ;Boehm, MF
视黄醇X受体：过氧化物酶体增殖性激活受体(RXR：PPAR)异源二聚体在调节糖(RXR/PPARy)和脂代谢(RXR/PPARpha)中起重要作用。在此之前，我们对具有(2E，4E，6Z)-3-methyl-7-(3，5-dialkyl-6-Eilkoxyphenyl)-octa-2，4，6-trienoic酸支架的选择性RXR调节剂进行了简明的构效关系研究。这些研究主要集中在2位烷氧基侧链上。我们设计和合成了一系列具有相同芳香核结构的新型RXR选择性调节剂，在三烯酸链上增加了一个环锁的6-7-Z-烯烃。本文报道了这些6，7-锁环戊烯、苯基、噻吩基、呋喃和吡啶-三烯酸衍生物的合成和构效关系研究。
Retinoid X receptor:peroxisome proliferative-activated receptor (RXR:PPAR) heterodimers play a critical role in the regulation of glucose (RXR/PPARy) and lipid metabolism (RXR/PPARalpha). Previously, we described a concise structure-activity relationship study of selective RXR modulators possessing a (2E,4E,6Z)-3-methyl-7-(3,5-dialkyl-6-Eilkoxyphenyl)-octa-2,4,6-trienoic acid scaffold. These studies were focused on the 2-position alkoxy side chain. We describe here the design and synthesis of a novel series of RXR selective modulators possessing the same aromatic core structure with the addition of a ring locked 6--7-Z-olefin on the trienoic acid moiety. The synthesis and structure- activity relationship studies of these 6,7-locked cyclopentenyl, phenyl, thienyl, furan, and pyridine-trienoic acid derivatives is presented herein.