Mueller, Rudolf published the artcileLerisetron Analogues with Antimalarial Properties: Synthesis, Structure-Activity Relationship Studies, and Biological Assessment, SDS of cas: 724710-02-5, the publication is ACS Omega (2020), 5(12), 6967-6982, database is CAplus and MEDLINE.
A phenotypic whole cell high-throughput screen against the asexual blood and liver stages of the malaria parasite identified a benzimidazole chem. series. Among the hits were the antiemetic benzimidazole drug Lerisetron 1 (IC50 NF54 = 0.81μM) and its methyl-substituted analog 2 (IC50 NF54 = 0.098μM). A medicinal chem. hit to lead effort led to the identification of chloro-substituted analog 3 with high potency against the drug-sensitive NF54 (IC50 NF54 = 0.062μM) and multidrug-resistant K1 (IC50 K1 = 0.054μM) strains of the human malaria parasite Plasmodium falciparum. Compounds 2 and 3 gratifyingly showed in vivo efficacy in both Plasmodium berghei and P. falciparum mouse models of malaria. Cardiotoxicity risk as expressed in strong inhibition of the human ether-a-go-go-related gene (hERG) potassium channel was identified as a major liability to address. This led to the synthesis and biol. assessment of around 60 analogs from which several compounds with improved antiplasmodial potency, relative to the lead compound 3, were identified.
ACS Omega published new progress about 724710-02-5. 724710-02-5 belongs to pyrazoles-derivatives, auxiliary class Pyrazole,Boronic acid and ester,Pyrazole,Boronic Acids,Boronic acid and ester, name is (1H-Pyrazol-5-yl)boronic acid, and the molecular formula is C3H5BN2O2, SDS of cas: 724710-02-5.
Referemce:
https://en.wikipedia.org/wiki/Pyrazole,
Pyrazoles – an overview | ScienceDirect Topics