1007881-21-1Relevant articles and documents
Highlights of the Structure-Activity Relationships of Benzimidazole Linked Pyrrolidines Leading to the Discovery of the Hepatitis C Virus NS5A Inhibitor Pibrentasvir (ABT-530)
Wagner, Rolf,Randolph, John T.,Patel, Sachin V.,Nelson, Lissa,Matulenko, Mark A.,Keddy, Ryan,Pratt, John K.,Liu, Dachun,Krueger, A. Chris,Donner, Pamela L.,Hutchinson, Douglas K.,Flentge, Charles,Betebenner, David,Rockway, Todd,Maring, Clarence J.,Ng, Teresa I.,Krishnan, Preethi,Pilot-Matias, Tami,Collins, Christine,Panchal, Neeta,Reisch, Thomas,Dekhtyar, Tatyana,Mondal, Rubina,Stolarik, Deanne F.,Gao, Yi,Gao, Wenqing,Beno, David A.,Kati, Warren M.
, p. 4052 - 4066 (2018/05/14)
Curative interferon and ribavirin sparing treatments for hepatitis C virus (HCV)-infected patients require a combination of mechanistically orthogonal direct acting antivirals. A shared component of these treatments is usually an HCV NS5A inhibitor. First generation FDA approved treatments, including the component NS5A inhibitors, do not exhibit equivalent efficacy against HCV virus genotypes 1-6. In particular, these first generation NS5A inhibitors tend to select for viral drug resistance. Ombitasvir is a first generation HCV NS5A inhibitor included as a key component of Viekira Pak for the treatment of patients with HCV genotype 1 infection. Since the launch of next generation HCV treatments, functional cure for genotype 1-6 HCV infections has been achieved, as well as shortened treatment duration across a wider spectrum of genotypes. In this paper, we show how we have modified the anchor, linker, and end-cap architecture of our NS5A inhibitor design template to discover a next generation NS5A inhibitor pibrentasvir (ABT-530), which exhibits potent inhibition of the replication of wild-type genotype 1-6 HCV replicons, as well as improved activity against replicon variants demonstrating resistance against first generation NS5A inhibitors.
HEPATITIS C VIRUS INHIBITORS
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Paragraph 0462-0463, (2017/07/05)
The present disclosure relates to compounds, compositions and methods for the treatment of hepatitis C virus (HCV) infection. Also disclosed are pharmaceutical compositions containing such compounds and methods for using these compounds in the treatment of HCV infection.
Matched and mixed cap derivatives in the tetracyclic indole class of HCV NS5A inhibitors
Dwyer, Michael P.,Keertikar, Kerry M.,Chen, Lei,Tong, Ling,Selyutin, Oleg,Nair, Anilkumar G.,Yu, Wensheng,Zhou, Guowei,Lavey, Brian J.,Yang, De-Yi,Wong, Michael,Kim, Seong Heon,Coburn, Craig A.,Rosenblum, Stuart B.,Zeng, Qingbei,Jiang, Yueheng,Shankar, Bandarpalle B.,Rizvi, Razia,Nomeir, Amin A.,Liu, Rong,Agrawal, Sony,Xia, Ellen,Kong, Rong,Zhai, Ying,Ingravallo, Paul,Asante-Appiah, Ernest,Kozlowski, Joseph A.
, p. 4106 - 4111 (2016/08/01)
A matched and mixed capping SAR study was conducted on the tetracyclic indole class of HCV NS5A inhibitors to examine the influence of modifications of this region on the overall HCV virologic resistance profiles.