Peat Andrew J, Boucheron Joyce A, Dickerson Scott H, Garrido Dulce, Mills Wendy, Peckham Jennifer, Preugschat Frank, Smalley Terrence, Schweiker Stephanie L, Wilson Jayme R, Wang Tony Y, Zhou Huiqiang Q, Thomson Stephen A
GlaxoSmithKline Research and Development, 5 Moore Drive, Research Triangle Park, NC 27709, USA.
Bioorg Med Chem Lett. 2004 May 3;14(9):2121-5. doi: 10.1016/j.bmcl.2004.02.036.
A series of [1-aryl-1H-pyrazolo[3,4-d]pyrimidin-4-yl]arylhydrazones were discovered as novel inhibitors glycogen synthase kinase-3 (GSK-3). Based on initial modeling a detailed SAR was constructed. Modification of the interior binding aryl ring (Ar(1)) determined this to be a tight binding region with little room for modification. As predicted from the model, a large variety of modifications could be incorporated into the hydrazone aryl ring. This work led to GSK-3 inhibitors in the low nano-molar range.
