864801-58-1Relevant academic research and scientific papers
P3-P4 ureas and reverse carbamates as potent HCV NS3 protease inhibitors: Effective transposition of the P4 hydrogen bond donor
Venables, Brian L.,Sin, Ny,Wang, Alan Xiangdong,Sun, Li-Qiang,Tu, Yong,Hernandez, Dennis,Sheaffer, Amy,Lee, Min,Dunaj, Cindy,Zhai, Guangzhi,Barry, Diana,Friborg, Jacques,Yu, Fei,Knipe, Jay,Sandquist, Jason,Falk, Paul,Parker, Dawn,Good, Andrew C.,Rajamani, Ramkumar,McPhee, Fiona,Meanwell, Nicholas A.,Scola, Paul M.
, p. 1853 - 1859 (2018)
A series of tripeptidic acylsulfonamide inhibitors of HCV NS3 protease were prepared that explored structure-activity relationships (SARs) at the P4 position, and their in vitro and in vivo properties were evaluated. Enhanced potency was observed in a ser
Toward the back-up of Boceprevir (SCH 503034): Discovery of new extended P4-capped ketoamide inhibitors of hepatitis C virus NS3 serine protease with improved potency and pharmacokinetic profiles
Bogen, Stéphane L.,Pan, Weidong,Ruan, Sumei,Nair, Latha G.,Arasappan, Ashok,Bennett, Frank,Chen, Kevin X.,Jao, Edwin,Venkatraman, Srikanth,Vibulbhan, Bancha,Liu, Rong,Cheng, Kuo-Chi,Guo, Zhuyan,Tong, Xiao,Saksena, Anil K.,Girijavallabhan, Viyyoor,Njoroge, F. George
scheme or table, p. 3679 - 3688 (2010/04/05)
Hepatitis C is the most prevalent liver disease. Viral hepatitis C (HCV), a small (+)-RNA virus, infects chronically an estimated 300 million people worldwide. Results of Phase I clinical studies with our first generation HCV inhibitor Boceprevir, SCH 503034 (1), presented at the 56th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD) were encouraging, and thus, additional human clinical studies are underway. In view of the positive data from our first generation compound, further work aimed at optimizing its overall profile was undertaken. Herein, we report that extension of our earlier inhibitor to the P4 pocket and optimization of the P1′ capping led to the discovery of new ketoamide inhibitors of the HCV NS3 serine protease with improved in vitro potency. In addition to being potent inhibitors of HCV subgenomic RNA replication, some of the new P4-capped inhibitors were also found to have improved PK profile.
