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Potent inhibitors of malarial P. Falciparum protein kinase G: Improving the cell activity of a series of imidazopyridines.

Authors :
Large JM
Birchall K
Bouloc NS
Merritt AT
Smiljanic-Hurley E
Tsagris DJ
Wheldon MC
Ansell KH
Coombs PJ
Kettleborough CA
Whalley D
Stewart LB
Bowyer PW
Baker DA
Osborne SA
Source :
Bioorganic & medicinal chemistry letters [Bioorg Med Chem Lett] 2019 Feb 01; Vol. 29 (3), pp. 509-514. Date of Electronic Publication: 2018 Nov 20.
Publication Year :
2019

Abstract

Development of a class of bicyclic inhibitors of the Plasmodium falciparum cyclic GMP-dependent protein kinase (PfPKG), starting from known compounds with activity against a related parasite PKG orthologue, is reported. Examination of key sub-structural elements led to new compounds with good levels of inhibitory activity against the recombinant kinase and in vitro activity against the parasite. Key examples were shown to possess encouraging in vitro ADME properties, and computational analysis provided valuable insight into the origins of the observed activity profiles.<br /> (Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Details

Language :
English
ISSN :
1464-3405
Volume :
29
Issue :
3
Database :
MEDLINE
Journal :
Bioorganic & medicinal chemistry letters
Publication Type :
Academic Journal
Accession number :
30553738
Full Text :
https://doi.org/10.1016/j.bmcl.2018.11.039