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Design and Synthesis of Brain Penetrant Trypanocidal N-Myristoyltransferase Inhibitors.

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.

SUBMITTER: Bayliss T

PROVIDER: S-EPMC5734605 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

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Design and Synthesis of Brain Penetrant Trypanocidal N-Myristoyltransferase Inhibitors.

Bayliss Tracy T Robinson David A DA Smith Victoria C VC Brand Stephen S McElroy Stuart P SP Torrie Leah S LS Mpamhanga Chido C Norval Suzanne S Stojanovski Laste L Brenk Ruth R Frearson Julie A JA Read Kevin D KD Gilbert Ian H IH Wyatt Paul G PG

Journal of medicinal chemistry 20171122 23

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. br ...[more]

PMID: 29125744

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A Molecular Hybridization Approach for the Design of Potent, Highly Selective, and Brain-Penetrant N-Myristoyltransferase Inhibitors.

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