N1,N1-Dimethyl-N3-(3-(trifluoromethyl)phenethyl)propane-1,3-diamine, a new lead for the treatment of human African trypanosomiasis

The natural product, convolutamine I (1), has anti-trypanosomal activity however it has a high molecular weight of 473 due to a presence of 3 bromine atoms. The synthesis of the natural product convolutamine I (1) together with its analogues are presented. A SAR study against Trypanosoma brucei brucei led to compounds with improved physico-chemical properties: lower molecular weight and lower log P while maintaining potency (with a slight 2-fold improvement). [Display omitted] •Synthesis of the anti-trypanosomal natural product convolutamine I was presented.•Convolutamine I has high MW (475 Da) with 3 bromine atoms.•Forty-one analogues were synthesized for structure–activity-relationship study.•Two hits with lower log P and lower MW displayed a 2-fold increase in activity.