Design and Synthesis of Brain Penetrant Trypanocidal N-Myristoyltransferase Inhibitors

  • J Med Chem. 2017 Dec 14;60(23):9790-9806. doi: 10.1021/acs.jmedchem.7b01255.
Tracy Bayliss  1 ,  David A Robinson  1 ,  Victoria C Smith  1 ,  Stephen Brand  1 ,  Stuart P McElroy  1 ,  Leah S Torrie  1 ,  Chido Mpamhanga  1 ,  Suzanne Norval  1 ,  Laste Stojanovski  1 ,  Ruth Brenk  1 ,  Julie A Frearson  1 ,  Kevin D Read  1 ,  Ian H Gilbert  1 ,  Paul G Wyatt  1
Affiliations
  • 1. Drug Discovery Unit, College of Life Sciences, University of Dundee , Sir James Black Centre, Dundee DD1 5EH, U.K.
PMID: 29125744 DOI: 10.1021/acs.jmedchem.7b01255
Abstract

N-myristoyltransferase (NMT) represents a promising drug target within the parasitic protozoa Trypanosoma brucei (T. brucei), the causative agent for human African trypanosomiasis (HAT) or sleeping sickness. We have previously validated T. brucei NMT as a promising druggable target for the treatment of HAT in both stages 1 and 2 of the disease. We report on the use of the previously reported DDD85646 (1) as a starting point for the design of a class of potent, brain penetrant inhibitors of T. brucei NMT.