1350909-17-9Relevant academic research and scientific papers
Arylsulfonamidopiperidone derivatives as a novel class of factor Xa inhibitors
Shi, Yan,O'Connor, Stephen P.,Sitkoff, Doree,Zhang, Jing,Shi, Mengxiao,Bisaha, Sharon N.,Wang, Ying,Li, Chi,Ruan, Zheming,Michael Lawrence,Klei, Herbert E.,Kish, Kevin,Liu, Eddie C.-K.,Seiler, Steve M.,Schweizer, Liang,Steinbacher, Thomas E.,Schumacher, William A.,Robl, Jeffrey A.,MacOr, John E.,Atwal, Karnail S.,Stein, Philip D.
, p. 7516 - 7521 (2011)
The design, synthesis and SAR of a novel class of valerolactam-based arylsulfonamides as potent and selective FXa inhibitors is reported. The arylsulfonamide-valerolactam scaffold was derived based on the proposed bioisosterism to the arylcyanoguanidine-caprolactam core in known FXa inhibitors. The SAR study led to compound 46 as the most potent FXa inhibitor in this series, with an IC50 of 7 nM and EC2×PT of 1.7 μM. The X-ray structure of compound 40 bound to FXa shows that the sulfonamide-valerolactam scaffold anchors the aryl group in the S1 and the novel acylcytisine pharmacophore in the S4 pockets.
