Design and Synthesis
of Brain Penetrant Trypanocidal N‑Myristoyltransferase
Inhibitors

Bayliss, Tracy; Robinson, David A.; Smith, Victoria C.; Brand, Stephen; McElroy, Stuart P.; Torrie, Leah S.; Mpamhanga, Chido; Norval, Suzanne; Stojanovski, Laste; Brenk, Ruth; Frearson, Julie A.; Read, Kevin D.; Gilbert, Ian H.; Wyatt, Paul G.

doi:10.1021/acs.jmedchem.7b01255.s001

jm7b01255_si_001.pdf (547.49 kB)

Design and Synthesis of Brain Penetrant Trypanocidal N‑Myristoyltransferase Inhibitors

journal contribution

posted on 2017-11-10, 00:00 authored by Tracy Bayliss, David A. Robinson, Victoria C. Smith, Stephen Brand, Stuart P. McElroy, Leah S. Torrie, Chido Mpamhanga, Suzanne Norval, Laste Stojanovski, Ruth Brenk, Julie A. Frearson, Kevin D. Read, Ian H. Gilbert, Paul G. Wyatt

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.