Optimization and structure–activity relationship of a series of 1-phenyl-1, 8-naphthyridin-4-one-3-carboxamides: Identification of MK-0873, a potent and effective PDE4 …

…, Z Huang, F Laliberté, S Laliberté, JA Mancini…

Index: Guay, Daniel; Boulet, Louise; Friesen, Richard W.; Girard, Mario; Hamel, Pierre; Huang, Zheng; Laliberte, France; Laliberte, Sebastien; Mancini, Joseph A.; Muise, Eric; Pon, Doug; Styhler, Angela Bioorganic and Medicinal Chemistry Letters, 2008 , vol. 18, # 20 p. 5554 - 5558

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Citation Number: 13

Abstract

A SAR study of a series of 1-phenyl-1, 8-naphthyridin-4-one-3-carboxamides is described. Optimization of the series was based on in vitro potency against PDE4, inhibition of the LPS- induced production of TNF-α in human whole blood and minimizing affinity for the hERG potassium channel. From these studies, compounds 18 and 20 (MK-0873) were identified as optimized PDE4 inhibitors with good overall in vitro and in vivo profiles and selected as ...