Synthesis and biological evaluation of α-aryl-α-tetralone derivatives as hepatitis C virus inhibitors

Dinesh Manvar; Talita de A Fernandes; Jorge L O Domingos; Erdenechimeg Baljinnyam; Amartya Basu; Eurides F T Junior; Paulo R R Costa; Neerja Kaushik-Basu

doi:10.1016/j.ejmech.2015.01.057

Synthesis and biological evaluation of α-aryl-α-tetralone derivatives as hepatitis C virus inhibitors

Eur J Med Chem. 2015 Mar 26:93:51-4. doi: 10.1016/j.ejmech.2015.01.057. Epub 2015 Jan 28.

Authors

Dinesh Manvar¹, Talita de A Fernandes², Jorge L O Domingos³, Erdenechimeg Baljinnyam¹, Amartya Basu¹, Eurides F T Junior², Paulo R R Costa⁴, Neerja Kaushik-Basu⁵

Affiliations

¹ Department of Microbiology, Biochemistry and Molecular Genetics, Rutgers-The State University of New Jersey, New Jersey Medical School, 185 South Orange Avenue, New Jersey 07103, USA.
² Laboratório de Química Bioorgânica, Instituto de Pesquisas de Produtos Naturais, Universidade Federal do Rio de Janeiro, Centro de Ciências da Saúde, Bloco H, Ilha da Cidade Universitária, 21941-590 Rio de Janeiro, RJ, Brazil.
³ Departamento de Química Orgânica, Centro de Tecnologia e Ciências, Universidade do Estado do Rio de Janeiro, Rua São Francisco Xavier 524, Pav. Haroldo Lisboa da Cunha - s 406 - Maracanã, 20550-900 Rio de Janeiro, RJ, Brazil.
⁴ Laboratório de Química Bioorgânica, Instituto de Pesquisas de Produtos Naturais, Universidade Federal do Rio de Janeiro, Centro de Ciências da Saúde, Bloco H, Ilha da Cidade Universitária, 21941-590 Rio de Janeiro, RJ, Brazil. Electronic address: prrcosta2011@gmail.com.
⁵ Department of Microbiology, Biochemistry and Molecular Genetics, Rutgers-The State University of New Jersey, New Jersey Medical School, 185 South Orange Avenue, New Jersey 07103, USA. Electronic address: kaushik@njms.rutgers.edu.

PMID: 25644675
DOI: 10.1016/j.ejmech.2015.01.057

Abstract

The synthesis of a novel series of 1-carba-isoflavanones through the α-arylation of α-tetralones is described. Several of these compounds demonstrated potent activity and selectivity in-vitro against HCV replicon reporter cells. Compound 10 (LQB-314) exhibited the best profile being active and selective in both replicon reporter cells (IC50 1.8 μM, SI > 111 and IC50 4.3 μM, SI > 46 in Huh7/Rep-Feo1b and Huh7.5-FGR-JC1-Rluc2A, respectively). Compound 3 (LQB-307) was the more potent and selective for Huh7.5-FGR-JC1-Rluc2A replicon reporter cells (IC50 1.5 μM, SI > 101.4).

Keywords: Alpha-aryl-alpha-tetralones; Hepatitis C virus inhibitors; Microwave irradiation; Palladium catalyzed arylation.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antiviral Agents / adverse effects
Antiviral Agents / chemical synthesis*
Antiviral Agents / chemistry
Antiviral Agents / pharmacology*
Cell Line, Tumor
Cell Survival / drug effects
Drug Design*
Genes, Reporter
Genotype
Hepacivirus / drug effects*
Hepacivirus / genetics
Humans
Luciferases, Renilla / genetics
RNA, Viral / genetics
Replicon / drug effects
Replicon / genetics
Tetralones / adverse effects
Tetralones / chemical synthesis*
Tetralones / chemistry
Tetralones / pharmacology*
Transfection
Virus Replication / drug effects

Substances

Antiviral Agents
RNA, Viral
Tetralones
Luciferases, Renilla