Synthesis and Anti‐Plasmodium Activity of Benzimidazole Analogues Structurally Related to Astemizole

• DOI: 10.1002/cmdc.201300172
• Publication Date: 2013-09-11T07:14:53Z
• Authors: Gheorghe Roman; Ian E. Crandall; Walter A. Szarek
• Keywords: Benzimidazole; Astemizole; Moiety; Isocoumarins; Plasmodium berghei

Abstract A series of compounds structurally related to astemizole were designed and synthesized with the goal determining their anti‐ Plasmodium activity. Several modifications structure, namely removal 4‐fluorobenzyl and/or 4‐methoxyphenethyl moieties, substitution benzene ring benzimidazole scaffold, replacement fluorine atom in group, variation 4‐aminopiperidine moiety, explored. In vitro evaluation activity these using ItG strain showed that some its similar derivatives have IC 50 values nanomolar range exhibit toxicity towards parasite over Chinese ovarian hamster (CHO) cells a selectivity as high 200. The presence secondary cyclic amine at position 2 chlorine positions 4 5 moiety are two resulted potent selective antimalarials based on astemizole.