Optimization of a tertiary alcohol series of phosphodiesterase-4 (PDE4) inhibitors: structure-activity relationship related to PDE4 inhibition and human ether-a-go-go …

…, R Frenette, M Girard, D Guay, Z Huang…

Index: Friesen, Richard W.; Ducharme, Yves; Ball, Richard G.; Blouin, Marc; Boulet, Louise; Cote, Bernard; Frenette, Richard; Girard, Mario; Guay, Daniel; Huang, Zheng; Jones, Thomas R.; Laliberte, France; Lynch, Joseph J.; Mancini, Joseph; Martins, Evelyn; Masson, Paul; Muise, Eric; Pon, Douglas J.; Siegl, Peter K. S.; Styhler, Angela; Tsou, Nancy N.; Turner, Mervyn J.; Young, Robert N.; Girardt, Yves Journal of Medicinal Chemistry, 2003 , vol. 46, # 12 p. 2413 - 2426

Full Text: HTML

Citation Number: 55

Abstract

A SAR study on the tertiary alcohol series of phosphodiesterase-4 (PDE4) inhibitors related to 1 is described. In addition to inhibitory potency against PDE4 and the lipopolysaccharide- induced production of TNFα in human whole blood, the binding affinity of these compounds for the human ether-a-go-go related gene (hERG) potassium channel (an in vitro measure for the potential to cause QTc prolongation) was assessed. Four key structural moieties in ...