Dipartimento di Scienze del Farmaco, Università degli Studi G. d'Annunzio, Chieti, Italy.
Bioorg Med Chem Lett. 2011 Aug 15;21(16):4869-72. doi: 10.1016/j.bmcl.2011.06.028.
The discovery of PPAR antagonists is emerging as an useful tool for elucidating the biological role of the receptor. Here we report the identification of N-(phenylsulfonyl)amides containing the benzothiazole scaffold, a novel class of potent PPARα antagonists obtained from chemical modification of carboxylic acid agonists. In this work, a group of phenylsulfonamides were synthesized and in vitro evaluated against the agonistic effect of GW7647; they showed an inhibitory effect on PPARα activation, with best compounds revealing a dose-dependent antagonistic profile. Some of these antagonists showed also an inhibitory effect on CPT1A pattern expression.
PPAR 拮抗剂的发现正成为阐明受体生物学功能的有用工具。在这里，我们报告了含有苯并噻唑支架的 N-(苯磺酰基)酰胺的鉴定，这是一类从羧酸激动剂化学修饰获得的新型强效 PPARα 拮抗剂。在这项工作中，合成了一组苯磺酰胺并对 GW7647 的激动作用进行了体外评估；它们对 PPARα 激活表现出抑制作用，最佳化合物显示出剂量依赖性拮抗作用。其中一些拮抗剂对 CPT1A 模式表达也表现出抑制作用。
