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ID: ALA4396957

Journal: Bioorg Med Chem Lett

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

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.

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.

CiteXplore: 31471167

DOI: 10.1016/j.bmcl.2019.08.014