Department of Medicinal Chemistry, Merck Research Laboratories, Rahway, NJ 07065, USA.
Bioorg Med Chem Lett. 2011 Mar 15;21(6):1890-5. doi: 10.1016/j.bmcl.2010.11.090. Epub 2010 Nov 25.
The development of 2-phenylbenzoxazoles as inhibitors of cholesteryl ester transfer protein (CETP) is described. Initial efforts aimed at engineering replacements for the aniline substructures in the benchmark molecule. Reversing the connectivity of the central aniline lead to a new class of 2-(4-carbonylphenyl)benzoxazoles. Structure-activity studies at the C-7 and terminal pyridine ring allowed for the optimization of potency and HDLc-raising efficacy in this new class of inhibitors. These efforts lead to the discovery of benzoxazole 11v, which raised HDLc by 24 mg/dl in our transgenic mouse PD model.
本文描述了 2-苯基苯并恶唑作为胆固醇酯转移蛋白（CETP）抑制剂的开发。最初的研究旨在对基准分子中的苯胺取代基进行工程改造。将中心苯胺的连接性颠倒过来，得到了一类新的 2-（4-羰基苯基）苯并恶唑。在 C-7 和末端吡啶环上进行的构效关系研究，使得在这一类抑制剂中优化了效力和升高 HDLc 的效果。这些努力导致了苯并恶唑 11v 的发现，它在我们的转基因 PD 模型小鼠中使 HDLc 升高了 24mg/dl。
