Department of Medicinal Chemistry, Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, CT 06877, USA.
Bioorg Med Chem Lett. 2010 Jun 15;20(12):3703-7. doi: 10.1016/j.bmcl.2010.04.078. Epub 2010 Apr 22.
A 270-membered library of trisubstituted ureas was synthesized and evaluated for inhibition of soluble epoxide hydrolase. Library design and reagent selection was guided by the use of a pharmacophore model and synthesis of the array was enabled with a general solid-phase method. This array approach facilitated multi-dimensional SAR around this series and identified functionality responsible for binding affinity, as well as opportunities for modulating the overall in vitro profiles of this class of soluble epoxide hydrolase inhibitors.
合成了一个由 270 个三取代脲组成的文库,并对其抑制可溶性环氧化物水解酶的活性进行了评估。文库的设计和试剂选择是基于药效团模型进行的,并且通过通用的固相合成方法来实现了该阵列的合成。这种方法促进了该系列的多维 SAR 研究,并确定了与结合亲和力相关的功能,以及调节这类可溶性环氧化物水解酶抑制剂整体体外特性的机会。