Pyrazolopyridines as a novel structural class of potent and selective PDE4 inhibitors

…, J Dawson, CJ Delves, PS Jones, M Lindvall…

Index: Hamblin, J. Nicole; Angell, Tony D.R.; Ballantine, Stuart P.; Cook, Caroline M.; Cooper, Anthony W.J.; Dawson, John; Delves, Christopher J.; Jones, Paul S.; Lindvall, Mika; Lucas, Fiona S.; Mitchell, Charlotte J.; Neu, Margarete Y.; Ranshaw, Lisa E.; Solanke, Yemisi E.; Somers, Don O.; Wiseman, Joanne O. Bioorganic and Medicinal Chemistry Letters, 2008 , vol. 18, # 14 p. 4237 - 4241

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Citation Number: 53

Abstract

Optimisation of a high-throughput screening hit resulted in the discovery of 4-(substituted amino)-1-alkyl-pyrazolo [3, 4-b] pyridine-5-carboxamides as potent and selective inhibitors of Phosphodiesterase 4 (PDE4). Herein, we describe early SAR studies around this novel template highlighting preferred substituents and rationalization of SAR through X-ray crystal structures of analogues bound to the PDE4 active site. Pyrazolopyridine 20a was found to ...