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

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. [Copyright &y& Elsevier]