Quinazolinone fungal efflux pump inhibitors. Part 3: (N-methyl)piperazine variants and pharmacokinetic optimization

Bioorg Med Chem Lett. 2007 May 15;17(10):2802-6. doi: 10.1016/j.bmcl.2007.02.047. Epub 2007 Feb 27.

Abstract

Further structure-activity relationships of a novel series of fungal efflux pump inhibitors with respect to potentiation of the activity of fluconazole against strains of C. albicans and C. glabrata over-expressing ABC-type efflux pumps are systematically explored. Rat protein binding and pharmacokinetics of selected analogues are reported.

MeSH terms

  • Animals
  • Antifungal Agents / blood
  • Antifungal Agents / chemistry
  • Antifungal Agents / pharmacokinetics
  • Antifungal Agents / pharmacology*
  • Candida albicans / drug effects
  • Hepatocytes / metabolism
  • Male
  • Membrane Transport Proteins / drug effects*
  • Membrane Transport Proteins / metabolism
  • Molecular Structure
  • Piperazine
  • Piperazines / chemistry*
  • Quinazolinones / blood
  • Quinazolinones / pharmacokinetics
  • Quinazolinones / pharmacology*
  • Rats
  • Rats, Sprague-Dawley
  • Serum / chemistry*
  • Structure-Activity Relationship

Substances

  • Antifungal Agents
  • Membrane Transport Proteins
  • Piperazines
  • Quinazolinones
  • Piperazine