Synthesis and antiviral evaluation of novel heteroarylpyrimidines analogs as HBV capsid effectors

Bioorg Med Chem Lett. 2017 Feb 15;27(4):904-910. doi: 10.1016/j.bmcl.2017.01.010. Epub 2017 Jan 6.

Abstract

New modifications to the scaffold of previously reported HBV capsid assembly effectors such as BAY 41-4109, HAP-12 and GLS4 were explored. The anti-HBV activity in the HepAD38 system, and cytotoxicity profiles of each of the new compounds has been assessed. Among them, five new iodo- and bromo-heteroarylpyrimidines analogs displayed anti-HBV activity in the low micromolar range.

Keywords: Capsid assembly effectors; HAP; HBV; Heteroarylpyrimidine.

MeSH terms

  • Animals
  • Antiviral Agents / chemical synthesis*
  • Antiviral Agents / chemistry
  • Antiviral Agents / pharmacology
  • Capsid Proteins / chemistry
  • Capsid Proteins / metabolism*
  • Cell Line
  • Cell Survival / drug effects
  • Chlorocebus aethiops
  • Hep G2 Cells
  • Hepatitis B virus / physiology*
  • Humans
  • Pyridines / chemistry
  • Pyrimidines / chemical synthesis
  • Pyrimidines / chemistry*
  • Pyrimidines / pharmacology
  • Structure-Activity Relationship
  • Vero Cells
  • Virus Replication / drug effects

Substances

  • Antiviral Agents
  • BAY 41-4109
  • Capsid Proteins
  • Pyridines
  • Pyrimidines