Jiang Wanlong, Tucci Fabio C, Tran Joe A, Fleck Beth A, Wen Jenny, Markison Stacy, Marinkovic Dragan, Chen Caroline W, Arellano Melissa, Hoare Sam R, Johns Michael, Foster Alan C, Saunders John, Chen Chen
Department of Medicinal Chemistry, Neurocrine Biosciences, Inc., 12790 El Camino Real, San Diego, CA 92130, USA.
Bioorg Med Chem Lett. 2007 Oct 15;17(20):5610-3. doi: 10.1016/j.bmcl.2007.07.097. Epub 2007 Aug 23.
A series of pyrrolidinones derived from phenylalaninepiperazines were synthesized and characterized as potent and selective antagonists of the melanocortin-4 receptor. In addition to their high binding affinities, these compounds displayed high functional potencies. 12a had a K(i) of 0.94 nM in binding and IC(50) of 21 nM in functional activity. 12a also demonstrated efficacy in a mouse cachexia model.
合成了一系列源自苯丙氨酸哌嗪的吡咯烷酮，并将其表征为强效且选择性的黑皮质素-4受体拮抗剂。除了具有高结合亲和力外，这些化合物还表现出高功能活性。12a的结合解离常数（K(i)）为0.94 nM，功能活性的半数抑制浓度（IC(50)）为21 nM。12a在小鼠恶病质模型中也显示出疗效。
