Tong Ling, Kim Seong Heon, Rosner Kristin, Yu Wensheng, Shankar Bandarpalle B, Chen Lei, Li Dansu, Dai Chaoyang, Girijavallabhan Vinay, Popovici-Muller Janeta, Yang Liping, Zhou Guowei, Kosinski Aneta, Siddiqui M Arshad, Shih Neng-Yang, Guo Zhuyan, Orth Peter, Chen Shiying, Lundell Daniel, Niu Xiaoda, Umland Shelby, Kozlowski Joseph A
Department of Discovery Chemistry, Merck & Co., Inc., 2000 Galloping Hill Road, Kenilworth, NJ 07033, USA.
Department of Discovery Chemistry, Merck & Co., Inc., 2000 Galloping Hill Road, Kenilworth, NJ 07033, USA.
Bioorg Med Chem Lett. 2017 Jul 15;27(14):3037-3042. doi: 10.1016/j.bmcl.2017.05.062. Epub 2017 May 22.
We have identified a series of hydantoin-derived TNF-a converting enzyme (TACE) inhibitors containing a pendant fused bi-heteroaryl group, which demonstrate sub-nanomolar potency (Ki), excellent activity in human whole blood assay, and improved DMPK profiles over prior series.
我们已经鉴定出一系列含有悬挂稠合双杂芳基的乙内酰脲衍生的肿瘤坏死因子-α转化酶（TACE）抑制剂，这些抑制剂显示出亚纳摩尔级别的效力（Ki），在人全血测定中具有优异的活性，并且与先前系列相比具有改善的药物代谢动力学（DMPK）特征。
