Document Detail


Optimization of Chloronitrobenzamides (CNBs) as Therapeutic Leads for Human African Trypanosomiasis (HAT).
MedLine Citation:
PMID:  23484493     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
We previously reported the discovery of the activity of chloronitrobenzamides (CNBs) against bloodstream forms of Trypanosoma brucei. Herein we disclose extensive structure-activity relationship and structure-property relationship studies aimed at identification of tractable early leads for clinical development. These studies revealed a promising lead compound, 18a, that exhibited nanomolar potency against T. brucei (EC50 = 27 nM for T. b. brucei, 7 nM for T. b. rhodesiense, and 2 nM for T. b. gambiense) with excellent selectivity for parasite cells relative to mammalian cell lines (EC50 > 25 µM). In addition compound 18a displayed suitable physiochemical characteristics and microsomal stability (t1/2 > 4 h for human and mouse) to justify pursuing in vivo studies.
Authors:
Jong Yeon Hwang; David C Smithson; Fangyi Zhu; Gloria Holbrook; Michele C Connelly; Marcel Kaiser; Reto Brun; R Kiplin Guy
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-3-13
Journal Detail:
Title:  Journal of medicinal chemistry     Volume:  -     ISSN:  1520-4804     ISO Abbreviation:  J. Med. Chem.     Publication Date:  2013 Mar 
Date Detail:
Created Date:  2013-3-14     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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