Discovery libraries targeting the major enzyme classes: the serine hydrolases.
Discovery libraries targeting the major enzyme classes: the serine hydrolases.
复制标题
针对主要酶类的发现文库：丝氨酸水解酶。
DOI：
10.1016/j.bmcl.2014.06.063
复制
发表时间：
2014
影响因子：
2.7
通讯作者：
Boger,DaleL
中科院分区：
文献类型：
--
作者：
Otrubova,Katerina;Srinivasan,Venkat;Boger,DaleL
制备了两个含有缺电子酰基苯胺或酰基吡唑的中度反应性脲文库，并作为候选丝氨酸水解酶抑制剂的筛选文库。在每个文库中都有一个小而强大的化合物子集，作为能够随后结构多样化的化学型片段筛选文库。吡唑基脲的精制提供了非常有效的不可逆脂肪酸酰胺水解酶（FAAH，显然ki = 100-200 pM）抑制剂，与先前公开的缺乏电子的苯胺基脲互补。
Two libraries of modestly reactive ureas containing either electron-deficient acyl anilines or acyl pyrazoles were prepared and are reported as screening libraries for candidate serine hydrolase inhibitors. Within each library is a small but powerful subset of compounds that serve as a chemotype fragment screening library capable of subsequent structural diversification. Elaboration of the pyrazole-based ureas provided remarkably potent irreversible inhibitors of fatty acid amide hydrolase (FAAH, apparentKi= 100–200 pM) complementary to those previously disclosed enlisting electron-deficient aniline-based ureas.