46 Design and Synthesis of N‐Myristoyltransferase Inhibitors:
A Novel Drug Target for Malaria
Mark D. Rackham*; Megan H. Wright; James A. Brannigan; Kaveri Rangachari; Anthony J. Wilkinson; Anthony A. Holder; Rita Tewari; Edward W. Tate; Robin J. Leatherbarrow Lead NMT Inhibitors3
Malaria
HN
Drug Target?
O
N N
S
N‐Myristoyltransferase (NMT)1
O
N
N
IMP‐0000320
•In vitro parasite killing
•Drug‐resistant cell lines
•Chemical Reporter Tagging
•In vitro pharmacokinetics
•In vivo parasite killing
Initial NMT Inhibitors2
PfNMT Ki : 832 nM HsNMT Ki : 3 200 nM
clogP: 4.0
1
*[email protected]
Tate, E. W.; Bell, A. S.; Rackham, M. D.; Wright, M. H. Parasitology 2013, DOI: 10.1017/S0031182013000450
2
Rackham, M. D. et al. J. Med. Chem. 2013, 56 (1), 371
3
Leatherbarrow, R. J.; Tate, E. W.; Yu, Z.; Rackham, M. D. WO/2013/083991