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ID: ALA1145600

Journal: Bioorg Med Chem Lett

Title: Molecular features crucial to the activity of pyrimidine benzamide-based thrombopoietin receptor agonists.

Authors: Reiter LA, Jones CS, Brissette WH, McCurdy SP, Abramov YA, Bordner J, DiCapua FM, Munchhof MJ, Rescek DM, Samardjiev IJ, Withka JM.

Abstract: The identification of small molecule modulators of biological processes mediated via protein-protein interactions has generally proved to be a challenging endeavor. In the case of the thrombopoietin receptor (TPOr), however, a number of small molecule types have been reported to display biological activity similar to that of the agonist protein TPO. Through a detailed analysis of structure-activity relationships, X-ray crystal structures, NMR coupling constants, nuclear Overhauser effects, and computational data, we have determined the agonism-inducing conformation of one series of small molecule TPOr agonists. The relationship of this agonism-inducing conformation to that of other series of TPO receptor agonists is discussed.

CiteXplore: 18396041

DOI: 10.1016/j.bmcl.2008.03.052