Discovery of Novel and Ligand-Efficient Inhibitors of Plasmodium falciparum and Plasmodium vivax N-Myristoyltransferase

TY - JOUR

T1 - Discovery of Novel and Ligand-Efficient Inhibitors of Plasmodium falciparum and Plasmodium vivax N-Myristoyltransferase

AU - Rackham, Mark D.

AU - Brannigan, James A.

AU - Moss, David K.

AU - Yu, Zhiyong

AU - Wilkinson, Anthony J.

AU - Holder, Anthony A.

AU - Tate, Edward W.

AU - Leatherbarrow, Robin J.

PY - 2013/1/10

Y1 - 2013/1/10

N2 - N-Myristoyltransferase (NMT) is an attractive antiprotozoan drug target. A lead-hopping approach was utilized in the design and synthesis of novel benzo[b]thiophene-containing inhibitors of Plasmodium falciparum (PO and Plasmodium vivax (Pv) NMT. These inhibitors are selective against Homo sapiens NMT1 (HsNMT), have excellent ligand efficiency (LE), and display antiparasitic activity in vitro. The binding mode of this series was determined by crystallography and shows a novel binding mode for the benzothiophene ring.

AB - N-Myristoyltransferase (NMT) is an attractive antiprotozoan drug target. A lead-hopping approach was utilized in the design and synthesis of novel benzo[b]thiophene-containing inhibitors of Plasmodium falciparum (PO and Plasmodium vivax (Pv) NMT. These inhibitors are selective against Homo sapiens NMT1 (HsNMT), have excellent ligand efficiency (LE), and display antiparasitic activity in vitro. The binding mode of this series was determined by crystallography and shows a novel binding mode for the benzothiophene ring.

KW - DESIGN

UR - http://www.scopus.com/inward/record.url?scp=84872315887&partnerID=8YFLogxK

U2 - 10.1021/jm301474t

DO - 10.1021/jm301474t

M3 - Article

SN - 0022-2623

VL - 56

SP - 371

EP - 375

JO - JOURNAL OF MEDICINAL CHEMISTRY

JF - JOURNAL OF MEDICINAL CHEMISTRY

IS - 1

ER -