1442679-99-3Relevant articles and documents
Discovery of carbohybrid-based 2-aminopyrimidine analogues as a new class of rapid-acting antimalarial agents using image-based cytological profiling assay
Lee, Sukjun,Lim, Donghyun,Lee, Eunyoung,Lee, Nakyung,Lee, Hong-Gun,Cechetto, Jonathan,Liuzzi, Michel,Freitas-Junior, Lucio H.,Song, Jin Sook,Bae, Myung Ae,Oh, Sangmi,Ayong, Lawrence,Park, Seung Bum
, p. 7425 - 7434 (2014)
New antimalarial agents that exhibit multistage activities against drug-resistant strains of malaria parasites represent good starting points for developing next-generation antimalarial therapies. To facilitate the progression of such agents into the development phase, we developed an image-based parasitological screening method for defining drug effects on different asexual life cycle stages of Plasmodium falciparum. High-throughput screening of a newly assembled diversity-oriented synthetic library using this approach led to the identification of carbohybrid-based 2-aminopyrimidine compounds with fast-acting growth inhibitory activities against three laboratory strains of multidrug-resistant P. falciparum. Our structure-activity relationship study led to the identification of two derivatives (8aA and 11aA) as the most promising antimalarial candidates (mean EC50of 0.130 and 0.096 μM against all three P. falciparum strains, selectivity indices >600, microsomal stabilities >80%, and mouse malaria ED50values of 0.32 and 0.12 mg/kg/day, respectively), targeting all major blood stages of multidrug-resistant P. falciparum parasites.
Synthesis of molecular frameworks containing two distinct heterocycles connected in a single molecule with enhanced three-dimensional shape diversity
Lim, Donghyun,Park, Seung Bum
, p. 7100 - 7108 (2013/06/27)
Herein, we report the synthesis of fused-triazole scaffolds that are connected by pyrimidines, pyrazoles, or pyrazolopyrimidines through carbohydrate-derived stereodivergent linkers. Pyrimidine-, pyrazole-, or pyrazolopyrimidine-based carbohybrids were co
