Document Detail


Diversity-Oriented Synthesis-Facilitated Medicinal Chemistry: Towards the Development of Novel Antimalarial Agents.
MedLine Citation:
PMID:  25211597     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
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.
Authors:
Eamon Comer; Jennifer A Beaudoin; Nobutaka Kato; Mark E Fitzgerald; Richard Wayne Heidebrecht; Maurice duPont Lee; Daniela Masi; Carol Mulrooney; Marion Mercier; Giovanni Muncipinto; Ann Rowley; Keila Crespo-Llado; Adelfa E Serrano; Amanda K Lukens; Roger C Wiegand; Dyann F Wirth; Michelle A Palmer; Michael A Foley; Benito Munoz; Christina A Scherer; Jeremy R Duvall; Stuart L Schreiber
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2014-9-11
Journal Detail:
Title:  Journal of medicinal chemistry     Volume:  -     ISSN:  1520-4804     ISO Abbreviation:  J. Med. Chem.     Publication Date:  2014 Sep 
Date Detail:
Created Date:  2014-9-11     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9716531     Medline TA:  J Med Chem     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
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