SAR of 2-amino and 2,4-diamino pyrimidines with in vivo efficacy against Trypanosoma brucei

A series of 2,4-diaminopyrimidines was investigated and compounds were found to have in vivo efficacy against Trypanosoma brucei in an acute mouse model. However, in vitro permeability data suggested the 2,4-diaminopyrimidenes would have poor permeability through the blood brain barrier. Consequentl...

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Bibliographic Details
Published in:	Bioorganic & medicinal chemistry letters 2011-05, Vol.21 (10), p.2816-2819
Main Authors:	Perales, Joe B., Freeman, Jennifer, Bacchi, Cyrus J., Bowling, Tana, Don, Robert, Gaukel, Eric, Mercer, Luke, Moore III, Joseph A., Nare, Bakela, Nguyen, Tien M., Noe, Robert A., Randolph, Ryan, Rewerts, Cindy, Wring, Stephen A., Yarlett, Nigel, Jacobs, Robert T.
Format:	Article
Language:	eng
Subjects:	2,4-Diamino pyrimidines Amines - chemistry Animal models Animals Antibiotics. Antiinfectious agents. Antiparasitic agents Antiparasitic agents Biological and medical sciences Blood-Brain Barrier Human african trypanosomiasis Inhibitory Concentration 50 Medical sciences Mice Molecular Structure Permeability Pharmacology. Drug treatments pyrimidines Pyrimidines - chemical synthesis Pyrimidines - chemistry Pyrimidines - pharmacology Quantitative Structure-Activity Relationship Trypanocidal Agents - chemical synthesis Trypanocidal Agents - chemistry Trypanocidal Agents - pharmacology Trypanosoma brucei Trypanosoma brucei brucei - drug effects
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Summary:	A series of 2,4-diaminopyrimidines was investigated and compounds were found to have in vivo efficacy against Trypanosoma brucei in an acute mouse model. However, in vitro permeability data suggested the 2,4-diaminopyrimidenes would have poor permeability through the blood brain barrier. Consequently a series of 4-desamino analogs were synthesized and found to have improved in vitro permeability.
ISSN:	0960-894X 1464-3405