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

Eur J Med Chem. 2014 Mar 3:74:541-51. doi: 10.1016/j.ejmech.2013.12.050. Epub 2014 Jan 9.

Abstract

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).

Keywords: Alkaloids; Anti-parasite; Anti-protozoa; Human African trypanosomiasis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Diamines / chemistry*
  • Diamines / pharmacology
  • Humans
  • Magnetic Resonance Spectroscopy
  • Phenethylamines / chemistry*
  • Phenethylamines / pharmacology
  • Spectrometry, Mass, Electrospray Ionization
  • Trypanocidal Agents / therapeutic use*
  • Trypanosomiasis, African / drug therapy*

Substances

  • Diamines
  • N1,N1-dimethyl-N3-(3-(trifluoromethyl)phenethyl)propane-1,3-diamine
  • Phenethylamines
  • Trypanocidal Agents