AI Article Synopsis
- The study discusses how a diversity-oriented synthesis (DOS) pathway sped up the development of a macrocyclic antimalarial agent, which was previously identified through this synthetic method.
- Researchers focused on altering both the structural features and appendages of the compound to produce a highly effective inhibitor of the malaria parasite P. falciparum, achieving better solubility and stability.
- The build/couple/pair (B/C/P) strategy was key in optimizing the medicinal chemistry for this antimalarial lead, enhancing its potential for therapeutic use.
Article 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.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4207553 | PMC |
| http://dx.doi.org/10.1021/jm500994n | DOI Listing |
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