医薬品化学

Azabicyclo-Nonane Pyrimidine Hybrid Synthesis and Antiprotozoal Activity

Abstract

Pascal Mäser *

Protozoan parasites are inhibited by 2,4-diaminopyrimidines and azabicyclo-nonanes. A series of fused hybrids were created and tested in vitro against malaria tropica and sleeping sickness pathogens. Compound activities and selectivities were heavily influenced by the substitution pattern of both ring systems as well as the position of the nitrogen atom in the bicycles. The most promising hybrids of 3-azabicyclo-nonane and 2-aminopyrimidine demonstrated submicromolar activity and high selectivity against P. falciparum NF54. A hybrid with pyrrolidino substitutions of the 2-azabicyclo-nonane and the pyrimidine moiety showed promising activity against the multiresistant P. falciparum K1 strain. A couple of hybrids of 2-azabicyclo-nonanes and 2-pyrimidines showed high activity and selectivity against Trypanosoma brucei rhodesiense.