Thieno [3, 2-d] pyrimidin-4 (3H)-one derivatives as PDK1 inhibitors discovered by fragment-based screening

…, A Poulsen, M Williams, S Blanchard, DM Ma…

Index: Lee, Angeline C.-H.; Ramanujulu, Pondy Murugappan; Poulsen, Anders; Williams, Meredith; Blanchard, Stephanie; Ma, Diana M.; Bonday, Zahid; Goh, Kay Lin; Goh, Kee Chuan; Goh, Miah Kiat; Wood, Jeanette; Dymock, Brian W. Bioorganic and Medicinal Chemistry Letters, 2012 , vol. 22, # 12 p. 4023 - 4027

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Citation Number: 3

Abstract

Ligand efficient fragments binding to PDK1 were identified by an NMR fragment-based screening approach. Computational modeling of the fragments bound to the active site led to the design and synthesis of a series of novel 6, 7-disubstituted thienopyrimidin-4-one compounds, with low micromolar inhibitory activity against PDK1 in a biochemical enzyme assay.