1. Discovery of 4-amino-5,6-biaryl-furo[2,3-d]pyrimidines as inhibitors of Lck: development of an expedient and divergent synthetic route and preliminary SAR
- Author
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Alan C. Cheng, Ryan White, Stephen Schneider, Joseph J. Nunes, John L. Buchanan, Jean Bemis, Faye Hsieh, William H. Buckner, Susan M. Turci, Matthew W. Martin, Christina Boucher, John Newcomb, Xin Huang, Xiaotian Zhu, Josie H. Lee, Theodore Faust, Erin F. DiMauro, David C. Mcgowan, and Teresa L. Marshall
- Subjects
Quantitative structure–activity relationship ,Stereochemistry ,Clinical Biochemistry ,Anti-Inflammatory Agents ,Pharmaceutical Science ,Crystallographic data ,Quantitative Structure-Activity Relationship ,Biochemistry ,Chemical synthesis ,Rats, Sprague-Dawley ,chemistry.chemical_compound ,Inhibitory Concentration 50 ,Drug Discovery ,Inhibitory concentration 50 ,Animals ,Humans ,Pharmacokinetics ,Lymphocytes ,Bifunctional ,Molecular Biology ,Protein Kinase Inhibitors ,Chemistry ,Organic Chemistry ,Rats ,Sprague dawley ,Pyrimidines ,Lymphocyte Specific Protein Tyrosine Kinase p56(lck) ,Molecular Medicine ,Interleukin-2 ,Lymphocyte Culture Test, Mixed ,Selectivity - Abstract
4-Amino-5,6-biaryl-furo[2,3-d]pyrimidines were identified as potent non-selective inhibitors of Lck. A novel, divergent, and practical synthetic route was developed to access derivatives from bifunctional intermediates. Lead optimization was guided by X-ray crystallographic data, and preliminary SAR led to the identification of compounds with improved cellular potency and selectivity.
- Published
- 2006