Merck Research Laboratories, Rahway, NJ 07065, USA.
Bioorg Med Chem Lett. 2011 Jan 1;21(1):558-61. doi: 10.1016/j.bmcl.2010.10.062. Epub 2010 Oct 20.
We describe structure-activity studies leading to the discovery of 2-arylbenzoxazole 3, the first in a series to raise serum high-density lipoprotein cholesterol levels in transgenic mice. Replacement of the 4-piperidinyloxy moiety with piperazinyl provided a more synthetically tractable lead, which upon optimization resulted in compound 4, an excellent inhibitor of cholesteryl ester transfer protein function with good pharmacokinetic properties and in vivo efficacy.
我们描述了结构-活性研究，这些研究导致发现了 2-芳基苯并恶唑 3，这是一系列能够提高转基因小鼠血清高密度脂蛋白胆固醇水平的化合物中的第一个。用哌嗪基取代 4-哌啶氧基部分提供了一个更具合成可行性的先导化合物，经过优化得到了化合物 4，它是一种极好的胆固醇酯转移蛋白功能抑制剂，具有良好的药代动力学性质和体内疗效。
