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Potent bicyclic inhibitors of malarial cGMP-dependent protein kinase: approaches to combining improvements in cell potency, selectivity and structural novelty

Year: 2019
Type: article
Abstract: Focussed studies on imidazopyridine inhibitors of Plasmodium falciparum cyclic GMP-dependent protein kinase (PfPKG) have significantly advanced the series towards desirable in vitro property space. LLE-based approaches towards combining improvements in cell potency, key physicochemical parameters and structural novelty are described, and a structure-based design hypothesis relating to substituent regiochemistry has directed efforts towards key examples with well-balanced potency, ADME and kinase selectivity profiles.
DOI: 10.1016/j.bmcl.2019.08.014
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
Language: English
Field: Medicine
Open Access status: hybrid
Estimated APC paid: $2,500
OpenAlex ID: W2969059477
FWCI: 1.605
Cites: 21
Cited by: 14
Related to: 10