Optimization and structure-activity relationship of a series of 1-phenyl-1,8-naphthyridin-4-one-3-carboxamides: identification of MK-0873, a potent an...
Basic Information
ID: ALA1142499
Journal: Bioorg Med Chem Lett
Title: 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 inhibitor.
Authors: Guay D, Boulet L, Friesen RW, Girard M, Hamel P, Huang Z, Laliberté F, Laliberté S, Mancini JA, Muise E, Pon D, Styhler A.
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-alpha 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 development candidates.
CiteXplore: 18835163
DOI: 10.1016/j.bmcl.2008.09.009
Patent ID: ┄