Identification of a pharmacophore for thrombopoietic activity of small, non-peptidyl molecules. 1. Discovery and optimization of salicylaldehyde thiosemicarbazone thrombopoietin mimics.

Kevin J Duffy, Anthony N Shaw, Evelyne Delorme, Susan B Dillon, Connie Erickson-Miller, Leslie Giampa, Yifang Huang, Richard M Keenan, Peter Lamb, Nannan Liu, Stephen G Miller, Alan T Price, Jon Rosen, Heather Smith, Kenneth J Wiggall, Lihua Zhang, Juan I Luengo

Index: J. Med. Chem. 45(17) , 3573-5, (2002)

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Abstract

High-throughput screening has resulted in the discovery of thiosemicarbazone thrombopoietin mimics. A shared pharmacophore hypothesis between this series and a previously identified class, the pyrazol-4-ylidenehydrazines, led to the rapid optimization of both potency and efficacy of the thiosemicarbazones. The application of high-throughput chemistry and purification techniques allowed for the rapid elucidation of structure-activity relationships.