title: Discovery of silyl proline containing HCV NS5A inhibitors with pan-genotype activity: SAR development.
abstract: HCV NS5A inhibitors have shown impressive in vitro potency profiles in HCV replicon assays thus making them attractive components for inclusion in an all oral fixed dose combination treatment regimen. Herein we describe the research efforts that led to the discovery of silyl proline containing HCV NS5A inhibitors such as 7e and 8a with pan-genotype activity profile and acceptable pharmacokinetic properties.
authors: Merck Research Laboratories, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA.
authors: Anilkumar G
authors: AG
authors: Nair
authors: Merck Research Laboratories, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA.
authors: Qingbei
authors: Q
authors: Zeng
authors: Merck Research Laboratories, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA.
authors: Oleg
authors: O
authors: Selyutin
authors: Merck Research Laboratories, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA.
authors: Stuart B
authors: SB
authors: Rosenblum
authors: Merck Research Laboratories, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA.
authors: Yueheng
authors: Y
authors: Jiang
authors: Merck Research Laboratories, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA.
authors: De-Yi
authors: DY
authors: Yang
authors: Merck Research Laboratories, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA.
authors: Kerry
authors: K
authors: Keertikar
authors: Merck Research Laboratories, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA.
authors: Guowei
authors: G
authors: Zhou
authors: Merck Research Laboratories, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA.
authors: Michael P
authors: MP
authors: Dwyer
authors: Merck Research Laboratories, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA.
authors: Seong Heon
authors: SH
authors: Kim
authors: Merck Research Laboratories, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA.
authors: Bandarpalle
authors: B
authors: Shankar
authors: Merck Research Laboratories, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA.
authors: Wensheng
authors: W
authors: Yu
authors: Merck Research Laboratories, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA.
authors: Ling
authors: L
authors: Tong
authors: Merck Research Laboratories, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA.
authors: Lei
authors: L
authors: Chen
authors: Merck Research Laboratories, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA.
authors: Robert
authors: R
authors: Mazzola
authors: Merck Research Laboratories, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA.
authors: John
authors: J
authors: Caldwell
authors: Merck Research Laboratories, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA.
authors: Haiqun
authors: H
authors: Tang
authors: Albany Molecular Research Inc., 26 Corporate Circle, Albany, NY 12203, USA.
authors: Melissa L
authors: ML
authors: Allard
authors: Albany Molecular Research Inc., 26 Corporate Circle, Albany, NY 12203, USA.
authors: Ronald N
authors: RN
authors: Buckle
authors: Albany Molecular Research Inc., 26 Corporate Circle, Albany, NY 12203, USA.
authors: Polivina Jolicia F
authors: PJ
authors: Gauuan
authors: Albany Molecular Research Inc., 26 Corporate Circle, Albany, NY 12203, USA.
authors: Christian L
authors: CL
authors: Holst
authors: Albany Molecular Research Inc., 26 Corporate Circle, Albany, NY 12203, USA.
authors: Gregory S
authors: GS
authors: Martin
authors: Albany Molecular Research Inc., 26 Corporate Circle, Albany, NY 12203, USA.
authors: Kannan P
authors: KP
authors: Naicker
authors: Albany Molecular Research Inc., 26 Corporate Circle, Albany, NY 12203, USA.
authors: Samuel
authors: S
authors: Vellekoop
authors: Merck Research Laboratories, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA.
authors: Sony
authors: S
authors: Agrawal
authors: Merck Research Laboratories, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA.
authors: Rong
authors: R
authors: Liu
authors: Merck Research Laboratories, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA.
authors: Rong
authors: R
authors: Kong
authors: Merck Research Laboratories, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA.
authors: Paul
authors: P
authors: Ingravallo
authors: Merck Research Laboratories, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA.
authors: Ellen
authors: E
authors: Xia
authors: Merck Research Laboratories, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA.
authors: Ying
authors: Y
authors: Zhai
authors: Merck Research Laboratories, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA.
authors: Amin
authors: A
authors: Nomeir
authors: Merck Research Laboratories, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA.
authors: Joseph A
authors: JA
authors: Kozlowski
mesh_terms: D000998:Antiviral Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D055808:Drug Discovery; D005838:Genotype; D016174:Hepacivirus / Q000187:drug effects* / Q000235:genetics*; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D011392:Proline / Q000031:analogs & derivatives*; D012821:Silanes / Q000737:chemistry* / Q000494:pharmacology; D013329:Structure-Activity Relationship; D017361:Viral Nonstructural Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics; D014779:Virus Replication / Q000187:drug effects; D012324:RNA-Dependent RNA Polymerase
chemical_list: D000998:Antiviral Agents; D011392:Proline; D012821:Silanes; D017361:Viral Nonstructural Proteins; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase
keywords: HCV; NS5a; Pan-genotype