β-分泌酶抑制剂的构象偏向性P3酰胺替代物

Conformationally biased P3 amide replacements of beta-secretase inhibitors.

作者信息

Stachel Shawn J, Coburn Craig A, Steele Thomas G, Crouthamel Min-Chi, Pietrak Beth L, Lai Ming-Tain, Holloway M Katharine, Munshi Sanjeev K, Graham Samuel L, Vacca Joseph P

机构信息

Department of Medicinal Chemistry, Merck Research Laboratories, West Point, PA 19486, USA.

出版信息

Bioorg Med Chem Lett. 2006 Feb;16(3):641-4. doi: 10.1016/j.bmcl.2005.10.032. Epub 2005 Nov 2.

DOI:10.1016/j.bmcl.2005.10.032

PMID:16263281

Abstract

We have synthesized and evaluated a series of conformationally biased P3 amide replacements based on an isophthalamide lead structure. The studies resulted in the identification of the beta-secretase inhibitor 7m which has an in vitro IC(50)=35 nM. The synthesis and biological activities of these compounds are described.

摘要

我们基于间苯二甲酰胺先导结构合成并评估了一系列构象偏向性的P3酰胺替代物。这些研究鉴定出了β-分泌酶抑制剂7m，其体外半数抑制浓度（IC50）=35 nM。本文描述了这些化合物的合成及生物活性。