1. Academic Validation
  2. Inhibition of human hepatitis B virus (HBV) by a novel non-nucleosidic compound in a transgenic mouse model

Inhibition of human hepatitis B virus (HBV) by a novel non-nucleosidic compound in a transgenic mouse model

  • Antiviral Res. 2002 May;54(2):69-78. doi: 10.1016/s0166-3542(01)00216-9.
O Weber 1 K-H Schlemmer E Hartmann Ina Hagelschuer A Paessens E Graef K Deres S Goldmann U Niewoehner J Stoltefuss D Haebich H Ruebsamen-Waigmann Stefan Wohlfeil
Affiliations

Affiliation

  • 1 Department of Antiinfective Research, Bayer AG Pharmaceutical Research Centre, D-42096 Wuppertal, Germany. olaf.weber@bayer.com
Abstract

BAY 41-4109 is a member of a class of heteroaryl-pyrimidines that was recently identified as potent inhibitors of human hepatitis B virus (HBV) replication. We have investigated the Antiviral activity of BAY 41-4109 (methyl (R)-4-(2-chloro-4-fluorophenyl)-2-(3,5-difluoro-2-pyridinyl)-6-methyl-1,4-dihydro-pyrimidine-5-carboxylate) in HBV-transgenic mice (Tg [HBV1.3 fsX(-)3'5']). Bay 41-4109 was administered per os using different schedules (b.i.d. or t.i.d. for up to 28 days) and dosages ranging from 3 to 30 mg/kg. The compound reduced viral DNA in the liver and in the plasma dose-dependently with efficacy comparable to 3TC. In contrast to 3TC-treated mice, we found a reduction of cytoplasmic hepatitis B virus core antigen (HBcAg) in liver sections of BAY 41-4109-treated mice, which indicated a different mode of action. Pharmacokinetic studies in mice have shown rapid absorption, a bioavailability of 30% and dose-proportional plasma concentrations. We conclude that BAY 41-4109 is a new anti-HBV drug candidate.

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