SAR of 2-amino and 2,4-diamino pyrimidines with in vivo efficacy against Trypanosoma brucei

Bioorg Med Chem Lett. 2011 May 15;21(10):2816-9. doi: 10.1016/j.bmcl.2011.03.097. Epub 2011 Apr 1.

Abstract

A series of 2,4-diaminopyrimidines was investigated and compounds were found to have in vivo efficacy against Trypanosoma brucei in an acute mouse model. However, in vitro permeability data suggested the 2,4-diaminopyrimidenes would have poor permeability through the blood brain barrier. Consequently a series of 4-desamino analogs were synthesized and found to have improved in vitro permeability.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amines / chemistry
  • Animals
  • Blood-Brain Barrier
  • Inhibitory Concentration 50
  • Mice
  • Molecular Structure
  • Permeability
  • Pyrimidines / chemical synthesis*
  • Pyrimidines / chemistry
  • Pyrimidines / pharmacology*
  • Quantitative Structure-Activity Relationship
  • Trypanocidal Agents / chemical synthesis
  • Trypanocidal Agents / chemistry
  • Trypanocidal Agents / pharmacology*
  • Trypanosoma brucei brucei / drug effects*

Substances

  • Amines
  • Pyrimidines
  • Trypanocidal Agents