Matched and mixed cap derivatives in the tetracyclic indole class of HCV NS5A inhibitors

Michael P Dwyer; Kerry M Keertikar; Lei Chen; Ling Tong; Oleg Selyutin; Anilkumar G Nair; Wensheng Yu; Guowei Zhou; Brian J Lavey; De-Yi Yang; Michael Wong; Seong Heon Kim; Craig A Coburn; Stuart B Rosenblum; Qingbei Zeng; Yueheng Jiang; Bandarpalle B Shankar; Razia Rizvi; Amin A Nomeir; Rong Liu; Sony Agrawal; Ellen Xia; Rong Kong; Ying Zhai; Paul Ingravallo; Ernest Asante-Appiah; Joseph A Kozlowski

doi:10.1016/j.bmcl.2016.06.063

Matched and mixed cap derivatives in the tetracyclic indole class of HCV NS5A inhibitors

Bioorg Med Chem Lett. 2016 Aug 15;26(16):4106-11. doi: 10.1016/j.bmcl.2016.06.063. Epub 2016 Jun 25.

Authors

Michael P Dwyer¹, Kerry M Keertikar², Lei Chen², Ling Tong², Oleg Selyutin², Anilkumar G Nair², Wensheng Yu², Guowei Zhou², Brian J Lavey², De-Yi Yang², Michael Wong², Seong Heon Kim², Craig A Coburn², Stuart B Rosenblum², Qingbei Zeng², Yueheng Jiang², Bandarpalle B Shankar², Razia Rizvi², Amin A Nomeir³, Rong Liu⁴, Sony Agrawal⁴, Ellen Xia⁴, Rong Kong⁴, Ying Zhai⁴, Paul Ingravallo⁴, Ernest Asante-Appiah⁴, Joseph A Kozlowski²

Affiliations

¹ Discovery Chemistry, Merck Research Laboratories, 2000 Galloping Hill Rd., Kenilworth, NJ 07033, USA. Electronic address: michael.dwyer@merck.com.
² Discovery Chemistry, Merck Research Laboratories, 2000 Galloping Hill Rd., Kenilworth, NJ 07033, USA.
³ Drug Metabolism, Merck Research Laboratories, 2000 Galloping Hill Rd., Kenilworth, NJ 07033, USA.
⁴ Discovery Biology, Merck Research Laboratories, 2000 Galloping Hill Rd., Kenilworth, NJ 07033, USA.

PMID: 27423481
DOI: 10.1016/j.bmcl.2016.06.063

Abstract

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.

Keywords: Capping; Hepatitis C; Indole; Infectious diseases; NS5A.

MeSH terms

Animals
Antiviral Agents / chemistry*
Antiviral Agents / metabolism
Antiviral Agents / pharmacology
Area Under Curve
Genotype
Half-Life
Hepacivirus / drug effects
Hepacivirus / genetics
Hepacivirus / metabolism*
Indoles / chemistry*
Indoles / metabolism
Indoles / pharmacology
ROC Curve
Rats
Structure-Activity Relationship
Viral Nonstructural Proteins / antagonists & inhibitors*
Viral Nonstructural Proteins / metabolism

Substances

Antiviral Agents
Indoles
Viral Nonstructural Proteins
NS-5 protein, hepatitis C virus