Potent bicyclic inhibitors of malarial cGMP-dependent protein kinase: approaches to combining improvements in cell potency, selectivity and structural novelty.
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ABSTRACT:
SUBMITTER: Large JM
PROVIDER: S-EPMC6857626 | biostudies-literature | 2019 Oct
REPOSITORIES: biostudies-literature
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Potent bicyclic inhibitors of malarial cGMP-dependent protein kinase: approaches to combining improvements in cell potency, selectivity and structural novelty.
Large Jonathan M JM Birchall Kristian K Bouloc Nathalie S NS Merritt Andy T AT Smiljanic-Hurley Ela E Tsagris Denise J DJ Wheldon Mary C MC Ansell Keith H KH Coombs Peter J PJ Kettleborough Catherine A CA Whalley David D Stewart Lindsay B LB Bowyer Paul W PW Baker David A DA Osborne Simon A SA
Bioorganic & medicinal chemistry letters 20190809 19
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 ...[more]
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