title: Discovery of ravidasvir (PPI-668) as a potent pan-genotypic HCV NS5A inhibitor.
abstract: This Letter describes the synthesis, representative structure activity relationship (SAR), activity and PK profiles of a series of functionalized benzimidazole-naphthylene-imidazole derivatives as HCV NS5A inhibitors. This effort successfully led to the discovery of ravidasvir (PPI-668), which has been well tolerated and shown high sustained viral response rates as a key component in all-oral combination regimens in multiple human clinical trials.
authors: Presidio Pharmaceuticals, Inc., 1700 Owens Street, Suite 585, San Francisco, CA 94158, USA. Electronic address: mzhong@myokardia.com.
authors: Min
authors: M
authors: Zhong
authors: Presidio Pharmaceuticals, Inc., 1700 Owens Street, Suite 585, San Francisco, CA 94158, USA.
authors: Eric
authors: E
authors: Peng
authors: Presidio Pharmaceuticals, Inc., 1700 Owens Street, Suite 585, San Francisco, CA 94158, USA.
authors: Ningwu
authors: N
authors: Huang
authors: Presidio Pharmaceuticals, Inc., 1700 Owens Street, Suite 585, San Francisco, CA 94158, USA.
authors: Qi
authors: Q
authors: Huang
authors: Presidio Pharmaceuticals, Inc., 1700 Owens Street, Suite 585, San Francisco, CA 94158, USA.
authors: Anja
authors: A
authors: Huq
authors: Presidio Pharmaceuticals, Inc., 1700 Owens Street, Suite 585, San Francisco, CA 94158, USA.
authors: Meiyen
authors: M
authors: Lau
authors: Presidio Pharmaceuticals, Inc., 1700 Owens Street, Suite 585, San Francisco, CA 94158, USA.
authors: Richard
authors: R
authors: Colonno
authors: Presidio Pharmaceuticals, Inc., 1700 Owens Street, Suite 585, San Francisco, CA 94158, USA. Electronic address: leping@assemblybio.com.
authors: Leping
authors: L
authors: Li
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000493:pharmacokinetics / Q000494:pharmacology*; D019540:Area Under Curve; D001562:Benzimidazoles / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D004285:Dogs; D055808:Drug Discovery; D005838:Genotype; D016174:Hepacivirus / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D008252:Macaca fascicularis; D051381:Rats; D013329:Structure-Activity Relationship; D014633:Valine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D017361:Viral Nonstructural Proteins / Q000037:antagonists & inhibitors*; D012324:RNA-Dependent RNA Polymerase
chemical_list: D000998:Antiviral Agents; D001562:Benzimidazoles; D014633:Valine; D017361:Viral Nonstructural Proteins; C000621711:ravidasvir; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase
keywords: Benzimidazole–naphthylene–imidazole derivatives; Hepatitis C virus; NS5A inhibitor; PPI-668; Ravidasvir