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.