864810-47-9Relevant academic research and scientific papers
P4 capped amides and lactams as HCV NS3 protease inhibitors with improved potency and DMPK profile
Nair, Latha G.,Sannigrahi, Mousumi,Bogen, Stephane,Pinto, Patrick,Chen, Kevin X.,Prongay, Andrew,Tong, Xiao,Cheng,Girijavallabhan, Viyyoor,George Njoroge
scheme or table, p. 567 - 570 (2010/05/02)
SAR studies on the extension of P3 unit of Boceprevir (1, SCH 503034) with amides and lactams and their synthesis is described. Extensive SAR studies resulted in the identification of 36 bearing 4, 4-dimethyl lactam as the new P4 cap unit with improved po
Novel potent inhibitors of hepatitis C virus (HCV) NS3 protease with cyclic sulfonyl P3 cappings
Chen, Kevin X.,Vibulbhan, Bancha,Yang, Weiying,Nair, Latha G.,Tong, Xiao,Cheng, Kuo-Chi,Njoroge, F. George
scheme or table, p. 1105 - 1109 (2009/08/07)
Extensive SAR studies of the P3 capping group led to the discovery of a series of potent inhibitors with sultam and cyclic sulfonyl urea moieties as the P3 capping. The bicyclic thiophene-sultam or phenyl-sultam cappings were selected for further SAR development. Modification at the P3 side chain determined that the tert-butyl group was the best choice at that position. Optimization of P1 residue significantly improved potency and selectivity. The combination of optimal moieties at all positions led to the discovery of compound 33. This compound had the best overall profile in potency and PK profile: excellent Ki* of 5.3 nM and activity in replicon (EC90) of 80 nM, extremely high selectivity of 6100, and a good rat PO AUC of 1.43 μM h.
Second-generation highly potent and selective inhibitors of the hepatitis C virus NS3 serine protease
Chen, Kevin X.,Nair, Latha,Vibulbhan, Bancha,Yang, Weiying,Arasappan, Ashok,Bogen, Stephane L.,Venkatraman, Srikanth,Bennett, Frank,Pan, Weidong,Blackman, Melissa L.,Padilla, Angela I.,Prongay, Andrew,Cheng, Kuo-Chi,Tong, Xiao,Shih, Neng-Yang,Njoroge, F. George
scheme or table, p. 1370 - 1379 (2009/12/26)
The hepatitis C virus (HCV) infection is a leading cause of chronic liver disease. The moderate efficacy along with side effects of the current pegylated interferon and ribavirin combination therapy underscores the need for more effective and safer new tr
Potent aza-peptide derived inhibitors of HCV NS3 protease
Venkatraman, Srikanth,Wu, Wanli,Shih, Neng-Yang,George Njoroge
scheme or table, p. 4760 - 4763 (2010/04/26)
Chronic hepatitis C infection is the primary cause for cirrhosis of the liver and hepatocellular carcinoma leading to liver failure and transplantation. The etiological agent hepatitis C virus produces a single positive strand RNA that is processed furthe
