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Trisubstituted Pyrimidines as Efficacious and Fast-Acting Antimalarials
In this paper we describe the optimization of a phenotypic hit against Plasmodium falciparum, based on a trisubstituted pyrimidine scaffold. This led to compounds with good pharmacokinetics and oral activity in a P. berghei mouse model of malaria. The most promising compound (13) showed a reduction in parasitemia of 96% when dosed at 30 mg/kg orally once a day for 4 days in the P. berghei mouse model of malaria. It also demonstrated a rapid rate of clearance of the erythrocytic stage of P. falciparum in the SCID mouse model with an ED90 of 11.7 mg/kg when dosed orally. Unfortunately, the compound is a potent inhibitor of cytochrome P450 enzymes, probably due to a 4-pyridyl substituent. Nevertheless, this is a lead molecule with a potentially useful antimalarial profile, which could either be further optimized or be used for target hunting.
Enzymes are biological catalysts that produce large increases in reaction rates and tend to be specific for certain reactants and products. I hope my blog about is helpful to your research. Recommanded Product: Thiomorpholine 1,1-dioxide
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Thiomorpholine – Wikipedia,
Thiomorpholine | C4H9NS – PubChem