Referenced in: none

Automatically associated channels: Kv11.1

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: Daniel Guay, Louise Boulet, Richard W Friesen, Mario Girard, Pierre Hamel, Zheng Huang, France Laliberté, Sébastien Laliberté, Joseph A Mancini, Eric Muise, Doug Pon, Angela Styhler

Journal, date & volume: Bioorg. Med. Chem. Lett., 2008 Oct 15 , 18, 5554-8

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/18835163

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.