Synthesis and in vitro evaluation of imidazopyridazines as novel inhibitors of the malarial kinase PfPK7.
A high-throughput screening campaign identified a number of imidazopyridazines as novel inhibitors of the malarial kinase PfPK7. Further synthetic chemistry efforts enabled the preparation of a number of analogues with promising in vitro potencies. Although these compounds show likely broad spectrum inhibitory activity, they represent a useful starting point for further chemical optimisation.
Bouloc
Nathalie
N
Drug Discovery Group, MRC Technology, 1-3 Burtonhole Lane, Mill Hill, London NW7 1AD, UK.
Large
Jonathan M
JM
Smiljanic
Ela
E
Whalley
David
D
Ansell
Keith H
KH
Edlin
Christopher D
CD
Bryans
Justin S
JS
D000818:Animals; D000962:Antimalarials / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D020650:Combinatorial Chemistry Techniques; D015195:Drug Design; D006801:Humans; D007093:Imidazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D007624:KB Cells; D020929:Mitogen-Activated Protein Kinase Kinases / Q000037:antagonists & inhibitors*; D015394:Molecular Structure; D010963:Plasmodium falciparum / Q000187:drug effects / Q000201:enzymology*; D015800:Protozoan Proteins / Q000037:antagonists & inhibitors*; D011724:Pyridazines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D000962:Antimalarials; D007093:Imidazoles; D015800:Protozoan Proteins; D011724:Pyridazines; C503375:PK7 protein, Plasmodium falciparum; D020929:Mitogen-Activated Protein Kinase Kinases