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Diversity-oriented synthesis-facilitated medicinal chemistry: toward the development of novel antimalarial agents.

ABSTRACT: Here, we describe medicinal chemistry that was accelerated by a diversity-oriented synthesis (DOS) pathway, and in vivo studies of our previously reported macrocyclic antimalarial agent that derived from the synthetic pathway. Structure-activity relationships that focused on both appendage and skeletal features yielded a nanomolar inhibitor of P. falciparum asexual blood-stage growth with improved solubility and microsomal stability and reduced hERG binding. The build/couple/pair (B/C/P) synthetic strategy, used in the preparation of the original screening library, facilitated medicinal chemistry optimization of the antimalarial lead.

SUBMITTER: Comer E

PROVIDER: S-EPMC4207553 | biostudies-literature | 2014 Oct

REPOSITORIES: biostudies-literature

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