Prioritization of compounds through pQSAR modeling led to the selection of two compounds for synthesis and experimental profiling. The two synthesized compounds exhibited potent antimalarial activity that was on par with approved antimalarials. The compounds also showed potent activity against the P. vivax PI(4)K kinase and exhibited low cytotoxic activity. While JAEGER overestimated the antimalarial activity, pQSAR's predictions were well within less than half a logarithm of the experimental values, thus emphasizing the need for further in-silico validation of ideas coming out from generative chemistry models with established computational chemistry methodologies.