Bravo Yalda, Baccei Christopher S, Broadhead Alex, Bundey Richard, Chen Austin, Clark Ryan, Correa Lucia, Jacintho Jason D, Lorrain Daniel S, Messmer Davorka, Stebbins Karin, Prasit Peppi, Stock Nicholas
Inception Sciences, 5871 Oberlin Drive Suite 100, San Diego, CA 92121, USA.
Inception Sciences, 5871 Oberlin Drive Suite 100, San Diego, CA 92121, USA.
Bioorg Med Chem Lett. 2014 May 15;24(10):2267-72. doi: 10.1016/j.bmcl.2014.03.090. Epub 2014 Apr 4.
The discovery and SAR of a novel series of potent and selective PPARα antagonists are herein described. Exploration of replacements for the labile acyl sulfonamide linker led to a biaryl sulfonamide series of which compound 33 proved to be suitable for further profiling in vivo. Compound 33 demonstrated excellent potency, selectivity against other nuclear hormone receptors, and good pharmacokinetics in mouse.
本文描述了一系列新型强效和选择性PPARα拮抗剂的发现及其构效关系。对不稳定的酰基磺酰胺连接子进行取代基探索，得到了联芳基磺酰胺系列化合物，其中化合物33被证明适合于进一步的体内研究。化合物33在小鼠体内表现出优异的活性、对其他核激素受体的选择性以及良好的药代动力学性质。
