title: Small-molecule inhibitors of hepatitis C virus (HCV) non-structural protein 5A (NS5A): a patent review (2010-2015).
abstract: Non-structural 5A (NS5A) protein has achieved a considerable attention as an attractive target for the treatment of hepatitis C (HCV). A number of novel NS5A inhibitors have been reported to date. Several drugs having favorable ADME properties and mild side effects were launched into the pharmaceutical market. For instance, daclatasvir was launched in 2014, elbasvir is currently undergoing registration, ledipasvir was launched in 2014 as a fixed-dose combination with sofosbuvir (NS5B inhibitor). Areas covered: Thomson integrity database and SciFinder database were used as a valuable source to collect the patents on small-molecule NS5A inhibitors. All the structures were ranked by the date of priority. Patent holder and antiviral activity for each scaffold claimed were summarized and presented in a convenient manner. A particular focus was placed on the best-in-class bis-pyrrolidine-containing NS5A inhibitors. Expert opinion: Several first generation NS5A inhibitors have recently progressed into advanced clinical trials and showed superior efficacy in reducing viral load in infected subjects. Therapy schemes of using these agents in combination with other established antiviral drugs with complementary mechanisms of action can address the emergence of resistance and poor therapeutic outcome frequently attributed to antiviral drugs.
authors.affiliation: a Department of Biological and Medical Physics , Moscow Institute of Physics and Technology (State University) , Dolgoprudny City , Moscow Region , Russia.|b Department of Computational and Medicinal Chemistry , ChemDiv , San Diego , CA , USA.|c Chemistry Department , Moscow State University , Moscow , Russia.
authors.forename: Yan A
authors.initials: YA
authors.lastname: Ivanenkov
authors.affiliation: a Department of Biological and Medical Physics , Moscow Institute of Physics and Technology (State University) , Dolgoprudny City , Moscow Region , Russia.
authors.forename: Vladimir A
authors.initials: VA
authors.lastname: Aladinskiy
authors.affiliation: a Department of Biological and Medical Physics , Moscow Institute of Physics and Technology (State University) , Dolgoprudny City , Moscow Region , Russia.
authors.forename: Nikolay A
authors.initials: NA
authors.lastname: Bushkov
authors.affiliation: a Department of Biological and Medical Physics , Moscow Institute of Physics and Technology (State University) , Dolgoprudny City , Moscow Region , Russia.
authors.forename: Andrey A
authors.initials: AA
authors.lastname: Ayginin
authors.affiliation: c Chemistry Department , Moscow State University , Moscow , Russia.
authors.forename: Alexander G
authors.initials: AG
authors.lastname: Majouga
authors.affiliation: b Department of Computational and Medicinal Chemistry , ChemDiv , San Diego , CA , USA.
authors.forename: Alexandre V
authors.initials: AV
authors.lastname: Ivachtchenko
mesh_terms: D000998:Antiviral Agents / Q000494:pharmacology*; D015195:Drug Design; D024882:Drug Resistance, Viral; D016174:Hepacivirus / Q000187:drug effects; D006526:Hepatitis C / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D010330:Patents as Topic; D017361:Viral Nonstructural Proteins / Q000037:antagonists & inhibitors*; D012324:RNA-Dependent RNA Polymerase
chemical_list: D000998:Antiviral Agents; D017361:Viral Nonstructural Proteins; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase
keywords: HCV; NS5A inhibitors; drug design; hepatitis C virus