N1-Alkyl pyrimidinediones as non-nucleoside inhibitors of HIV-1 reverse transcriptase

Bioorg Med Chem Lett. 2010 Mar 1;20(5):1589-92. doi: 10.1016/j.bmcl.2010.01.085. Epub 2010 Jan 21.

Abstract

A series of N1-alkyl pyrimidinediones were designed, synthesized and evaluated as HIV-1 non-nucleoside reverse transcriptase inhibitors (NNRTIs). Our efforts identified compound 10b, which represents the lead compound in this series with pharmacokinetics and antiviral potency that may support once-daily dosing.

MeSH terms

  • Animals
  • Anti-HIV Agents / chemical synthesis
  • Anti-HIV Agents / chemistry*
  • Anti-HIV Agents / pharmacokinetics
  • Binding Sites
  • Crystallography, X-Ray
  • Dogs
  • HIV Reverse Transcriptase / chemistry*
  • HIV Reverse Transcriptase / metabolism
  • Humans
  • Microsomes / metabolism
  • Pyrimidinones / chemical synthesis
  • Pyrimidinones / chemistry*
  • Pyrimidinones / pharmacokinetics
  • Reverse Transcriptase Inhibitors / chemical synthesis
  • Reverse Transcriptase Inhibitors / chemistry*
  • Reverse Transcriptase Inhibitors / pharmacokinetics
  • Structure-Activity Relationship
  • Thymine / analogs & derivatives*
  • Thymine / chemical synthesis
  • Thymine / chemistry
  • Thymine / pharmacokinetics

Substances

  • Anti-HIV Agents
  • Pyrimidinones
  • Reverse Transcriptase Inhibitors
  • reverse transcriptase, Human immunodeficiency virus 1
  • HIV Reverse Transcriptase
  • Thymine