Breslin Henry J, Miskowski Tamara A, Kukla Michael J, De Winter Hans L, Somers Maria V F, Roevens Peter W M, Kavash Robert W
Johnson & Johnson Pharmaceutical Research & Development, LLC, Welsh and McKean Roads, PO Box 776, Spring House, PA 19477-0776, USA.
Bioorg Med Chem Lett. 2003 Dec 15;13(24):4467-71. doi: 10.1016/j.bmcl.2003.09.014.
We have systematically explored the structure-activity relationship (SAR) for a series of compounds 2 as inhibitors of tripeptidyl-peptidase II (TPP II), a serine protease responsible for the degradation of cholecystokinin-8 (CCK-8). This SAR evaluation of the core structure 2 suggest a fairly restrictive pharmacophore for such related structures, but has yielded a limited set of compounds (2b, 2c, 2d, 2s, and 2t) with potent TPP II inhibitory activity (IC(50) 4-11 nM).
我们系统地研究了一系列化合物2作为三肽基肽酶II（TPP II）抑制剂的构效关系（SAR），TPP II是一种负责降解胆囊收缩素-8（CCK-8）的丝氨酸蛋白酶。对核心结构2的这种SAR评估表明，此类相关结构具有相当严格的药效团，但仅产生了一组有限的具有强效TPP II抑制活性（IC(50)为4-11 nM）的化合物（2b、2c、2d、2s和2t）。
