Design and synthesis of substituted phenylpropanoic acid derivatives as human peroxisome proliferator-activated receptor α/δ dual agonists
Design and synthesis of substituted phenylpropanoic acid derivatives as human peroxisome proliferator-activated receptor α/δ dual agonists
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DOI：
10.1016/j.bmcl.2005.10.049
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发表时间：
2006-02
影响因子：
2.7
通讯作者：
Jun-ichi Kasuga;M. Makishima;Y. Hashimoto;H. Miyachi
中科院分区：
文献类型：
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作者：
Jun-ichi Kasuga;M. Makishima;Y. Hashimoto;H. Miyachi
制备了一系列苯丙酸作为过氧化物酶体增殖物激活受体(PPAR) α和δ的候选双激动剂。构效关系研究表明，连接体部分的形状和远苯环取代基的性质对PPAR亚型转激活的效力和选择性起关键作用。旋光性α-乙基苯基丙烷酸衍生物被鉴定为有效的人PPAR α和δ双激动剂，具有治疗代谢综合征的潜力。
A series of phenylpropanoic acids was prepared as candidate dual agonists of peroxisome proliferator-activated receptors (PPAR) α and δ. Structure–activity relationship studies indicated that the shape of the linker moiety and the nature of the substituent at the distal benzene ring play key roles in determining the potency and selectivity of PPAR subtype transactivation. Optically active α-ethylphenylpropanoic acid derivatives were identified as potent human PPAR α and δ dual agonists with potential for the treatment of metabolic syndrome.