7H-Pyrrolo[2,3-d]pyrimidine-4-amines as Potential Inhibitors of Plasmodium falciparum Calcium-Dependent Protein Kinases.

A series of pyrrolo[2,3-d]pyrimidines were designed in silico as potential bumped kinase inhibitors targeting P. falciparum calcium dependent protein kinase 4 (PfCDPK4), with the potential to inhibit PfCDPK1 based on earlier studies of the two kinases. A small series of these compounds were prepared and assessed for inhibitory activity against PfCDPK4 and PfCDPK1 in vitro. Four of the compounds displayed promising inhibitory activity against either PfCDPK4 (IC 50 =0.210-0.530 μM), or PfCDPK1 (IC 50 =0.589 μM). These data will enable optimisation of the molecular model to better predict inhibitory activity against PfCDPK4.