作为小分子 BACE1 抑制剂的吡啶基氨乙内酰脲。
Pyridinyl aminohydantoins as small molecule BACE1 inhibitors.
机构信息
Department of Chemical Sciences, Wyeth Research, CN 8000, Princeton, NJ 08543-8000, United States.
出版信息
Bioorg Med Chem Lett. 2010 Apr 1;20(7):2326-9. doi: 10.1016/j.bmcl.2010.01.136. Epub 2010 Feb 12.
PMID:20202842
Abstract
A novel class of pyridinyl aminohydantoins was designed and prepared as highly potent BACE1 inhibitors. Compound (S)-4g showed excellent potency with IC(50) of 20 nM for BACE1. X-ray crystallography indicated that the interaction between pyridine nitrogen and the tryptophan Trp76 was a key feature in the S2' region of the enzyme that contributed to increased potency.
摘要
设计并合成了一类新型的吡啶基氨甲酰基乙内酰脲作为强效的 BACE1 抑制剂。化合物 (S)-4g 对 BACE1 表现出优异的抑制活性，IC50 为 20 nM。X 射线晶体学表明，吡啶氮与色氨酸 Trp76 之间的相互作用是酶 S2' 区域的一个关键特征，有助于提高化合物的活性。
Zotero 插件