Lead Optimization of TgCDPK1 Inhibitors for the Treatment of Toxoplasmosis - PubMed
4 hours ago
- #Drug Discovery
- #Toxoplasmosis
- #Kinase Inhibitors
- Lead optimization of biaryl-substituted pyrazolopyrimidine inhibitors targeting TgCDPK1 for toxoplasmosis treatment.
- Inhibitors show excellent potency against TgCDPK1 enzyme and antiparasitic activity in vitro.
- Compounds optimized for metabolic stability, reduced plasma protein binding, decreased efflux, and improved pharmacokinetics.
- Several inhibitors exhibit desirable pharmacokinetics with high oral bioavailability, low clearance, and extended half-life.
- Compound 16c identified as a promising preclinical candidate after testing in acute infection models in mice.