当前位置： SCI文献检索 > JOURNAL OF MEDICINAL CHEMISTRY期刊下所有文献 > Cyclic sulfones as novel P3-caps for hepatitis C virus NS3/4A (HCV NS3/4A) protease inhibitors: synthesis and evaluation of inhibitors with improved potency and pharmacokinetic profiles.

Cyclic sulfones as novel P3-caps for hepatitis C virus NS3/4A (HCV NS3/4A) protease inhibitors: synthesis and evaluation of inhibitors with improved potency and pharmacokinetic profiles.

Abstract：

:HCV infection affects more than 170 million people worldwide and many of those patients will reach the end stage complications of the disease which include hepatocarcinoma and liver failure. The success rate for treatment of patients infected with genotype-1 is about 40%. Therefore, novel treatments are needed to combat the infection. The HCV NS3 protease inhibitor Boceprevir (1) was reported by our research group and efforts continue for the discovery of more potent compounds with improved pharmacokinetic profiles. A new series of HCV NS3 protease inhibitors having a cyclic sulfone P3-cap have been discovered. Compounds 43 and 44 showed K(i)* values in the single-digit nM range and their cellular potency was improved by 10-fold compared to 1. The pharmacokinetic profiles of 43 and 44 in rats and monkeys were also improved to achieve higher plasma levels after oral administration.

journal_name

J Med Chem

journal_title

Journal of medicinal chemistry

authors

Velázquez F,Sannigrahi M,Bennett F,Lovey RG,Arasappan A,Bogen S,Nair L,Venkatraman S,Blackman M,Hendrata S,Huang Y,Huelgas R,Pinto P,Cheng KC,Tong X,McPhail AT,Njoroge FG

doi

10.1021/jm9016027

subject

Has Abstract

pub_date

2010-04-22 00:00:00

pages

3075-85

issue

8

eissn

0022-2623

issn

1520-4804

journal_volume

53

pub_type

杂志文章

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