Design, synthesis and in vitro evaluation of novel chroman-4-one, chroman, and 2H-chromene derivatives as human rhinovirus capsid-binding inhibitors

Bioorg Med Chem. 2011 Dec 15;19(24):7357-64. doi: 10.1016/j.bmc.2011.10.060. Epub 2011 Oct 26.

Abstract

As part of an effort to generate broad-spectrum inhibitors of rhinovirus replication, novel series of (E)-3-[(E)-3-phenylallylidene]chroman-4-ones 1a-e, (E)-3-(3-phenylprop-2-yn-1-ylidene)chroman-4-ones 2a and 2b, (Z)-3-[(E)-3-phenylallylidene]chromans 3a-e, and (E)-3-(3-phenylprop-1-en-1-yl)-2H-chromenes 4a-d were designed and synthesized. All the compounds were tested in vitro for their efficacy against infection by human rhinovirus (HRV) 1B and 14, two representative serotypes for rhinovirus group B and A, respectively. Most of the analogues were found to be potent and selective inhibitors of both HRVs, although HRV 1B was generally more susceptible than HRV 14. Mechanism of action studies of (E)-6-chloro-3-(3-phenylprop-1-en-1-yl)-2H-chromene 4b, the most potent compound on HRV 1B infection, suggested that 4b behaves as a capsid-binder probably acting at the uncoating level.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antiviral Agents / chemical synthesis
  • Antiviral Agents / chemistry
  • Antiviral Agents / pharmacology*
  • Benzopyrans / chemical synthesis
  • Benzopyrans / chemistry
  • Benzopyrans / pharmacology*
  • Capsid / metabolism*
  • Chromans / chemical synthesis
  • Chromans / chemistry
  • Chromans / pharmacology*
  • Drug Design*
  • HeLa Cells
  • Humans
  • Picornaviridae Infections / drug therapy
  • Rhinovirus / drug effects*

Substances

  • 5,7-dimethoxy-2-methyl-2H-benzopyran
  • Antiviral Agents
  • Benzopyrans
  • Chromans