N-（3-（苯基氨基甲酰基）芳基嘧啶）-5-羧酰胺作为Lck的强效和选择性抑制剂：结构、合成及构效关系

N-(3-(phenylcarbamoyl)arylpyrimidine)-5-carboxamides as potent and selective inhibitors of Lck: structure, synthesis and SAR.

作者信息

Deak Holly L, Newcomb John R, Nunes Joseph J, Boucher Christina, Cheng Alan C, DiMauro Erin F, Epstein Linda F, Gallant Paul, Hodous Brian L, Huang Xin, Lee Josie H, Patel Vinod F, Schneider Stephen, Turci Susan M, Zhu Xiaotian

机构信息

Department of Medicinal Chemistry, Amgen Inc., One Kendall Square, Building 1000, Cambridge, MA 02139, USA.

出版信息

Bioorg Med Chem Lett. 2008 Feb 1;18(3):1172-6. doi: 10.1016/j.bmcl.2007.11.123. Epub 2007 Dec 5.

DOI:10.1016/j.bmcl.2007.11.123

Abstract

N-3-(Phenylcarbamoyl)arylpyrimidine-5-carboxamides are a novel class of selective Lck inhibitors. This series of compounds derives its selectivity from a hydrogen bond with the gatekeeper Thr316 of the enzyme. X-ray co-crystal structural data, structure-activity relationships, and the synthesis of these inhibitors are reported herein.

摘要

N-3-(苯基氨基甲酰基)芳基嘧啶-5-甲酰胺是一类新型的选择性Lck抑制剂。该系列化合物的选择性源于与该酶的守门人苏氨酸316形成的氢键。本文报道了这些抑制剂的X射线共晶体结构数据、构效关系及合成方法。

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