| Literature DB >> 24712864 |
Yan Lou1, Xiaochun Han, Andreas Kuglstatter, Rama K Kondru, Zachary K Sweeney, Michael Soth, Joel McIntosh, Renee Litman, Judy Suh, Buelent Kocer, Dana Davis, Jaehyeon Park, Sandra Frauchiger, Nolan Dewdney, Hasim Zecic, Joshua P Taygerly, Keshab Sarma, Junbae Hong, Ronald J Hill, Tobias Gabriel, David M Goldstein, Timothy D Owens.
Abstract
Structure-based drug design was used to guide the optimization of a series of selective BTK inhibitors as potential treatments for Rheumatoid arthritis. Highlights include the introduction of a benzyl alcohol group and a fluorine substitution, each of which resulted in over 10-fold increase in activity. Concurrent optimization of drug-like properties led to compound 1 (RN486) ( J. Pharmacol. Exp. Ther. 2012 , 341 , 90 ), which was selected for advanced preclinical characterization based on its favorable properties.Entities:
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Year: 2014 PMID： 24712864 DOI： 10.1021/jm500305p
Source DB: PubMed Journal: J Med Chem ISSN： 0022-2623 Impact factor: 7.446