2. Academic Validation
  3. Discovery of potent macrocyclic HCV NS5A inhibitors

Discovery of potent macrocyclic HCV NS5A inhibitors

  • Bioorg Med Chem Lett. 2016 Aug 1;26(15):3793-9. doi: 10.1016/j.bmcl.2016.05.042.
Wensheng Yu 1,  Bancha Vibulbhan 2,  Stuart B Rosenblum 2,  Gregory S Martin 3,  A Samuel Vellekoop 3,  Christian L Holst 3,  Craig A Coburn 4,  Michael Wong 2,  Oleg Selyutin 2,  Tao Ji 5,  Bin Zhong 5,  Bin Hu 5,  Lei Chen 2,  Michael P Dwyer 2,  Yueheng Jiang 2,  Anilkumar G Nair 2,  Ling Tong 2,  Qingbei Zeng 2,  Sony Agrawal 6,  Donna Carr 6,  Laura Rokosz 6,  Rong Liu 7,  Stephanie Curry 7,  Patricia McMonagle 7,  Paul Ingravallo 7,  Fred Lahser 7,  Ernest Asante-Appiah 7,  James Fells 8,  Joseph A Kozlowski 2
Affiliations

Affiliations

  • 1 Department of Medicinal Chemistry, Merck Research Laboratories, 126 E. Lincoln Avenue, Rahway, NJ 07065, USA. Electronic address: wensheng.yu@merck.com.
  • 2 Department of Medicinal Chemistry, Merck Research Laboratories, 126 E. Lincoln Avenue, Rahway, NJ 07065, USA.
  • 3 Albany Molecular Research Inc., 26 Corporate Circle, Albany, NY 12203, USA.
  • 4 Department of Medicinal Chemistry, Merck Research Laboratories, 770 Sumneytown Pike, West Point, PA 19486, USA.
  • 5 WuXi AppTec, 288 Fute Zhong Road, Shanghai 200131, China.
  • 6 Department of In Vitro Pharmacology, Merck Research Laboratories, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA.
  • 7 Department of Infectious Diseases, Merck Research Laboratories, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA.
  • 8 Department of Structural Chemistry, Merck Research Laboratories, 126 E. Lincoln Avenue, Rahway, NJ 07065 USA.
PMID: 27282743 DOI: 10.1016/j.bmcl.2016.05.042
Abstract

HCV NS5A inhibitors have demonstrated impressive in vitro virologic profiles in HCV replicon assays and robust HCV RNA titer reduction in the clinic making them attractive components for inclusion in an all oral fixed-dose combination (FDC) regimen for the treatment of HCV Infection. Merck's effort in this area identified MK-4882 and MK-8325 as early development leads. Herein, we describe the discovery of potent macrocyclic NS5A inhibitors bearing the MK-8325 or MK-4882 core structure.

Keywords

DAA; HCV NS5A inhibitor; HCV infection; MK-4882; MK-8325; Macrocycle.

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