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Potent inhibitors of malarial P. Falciparum protein kinase G: Improving the cell activity of a series of imidazopyridines |
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| Authors: | Jonathan M. Large Kristian Birchall Nathalie S. Bouloc Andy T. Merritt Ela Smiljanic-Hurley Denise J. Tsagris Mary C. Wheldon Keith H. Ansell Peter J. Coombs Catherine A. Kettleborough David Whalley Lindsay B. Stewart Paul W. Bowyer David A. Baker Simon A. Osborne |
| Affiliation: | 1. Centre for Therapeutics Discovery, LifeArc, Accelerator Building, Open Innovation Campus, Stevenage SG1 2FX, UK;2. Faculty of Infectious and Tropical Diseases, London School of Hygiene & Tropical Medicine, Keppel Street, London WC1E 7HT, UK |
| 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. |
| Keywords: | Malaria Protein kinase G Imidazopyridine SAR |
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