303165-22-2Relevant academic research and scientific papers
Optimization of a tertiary alcohol series of phosphodiesterase-4 (PDE4) inhibitors: Structure-activity relationship related to PDE4 inhibition and human ether-a-go-go related gene potassium channel binding affinity
Friesen, Richard W.,Ducharme, Yves,Ball, Richard G.,Blouin, Marc,Boulet, Louise,C?té, Bernard,Frenette, Richard,Girard, Mario,Guay, Daniel,Huang, Zheng,Jones, Thomas R.,Laliberté, 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
, p. 2413 - 2426 (2007/10/03)
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
Substituted aminopyridines as potent and selective phosphodiesterase-4 inhibitors
Cote, Bernard,Frenette, Richard,Prescott, Sylvie,Blouin, Marc,Brideau, Christine,Ducharme, Yves,Friesen, Richard W.,Laliberte, France,Masson, Paul,Styhler, Angela,Girard, Yves
, p. 741 - 744 (2007/10/03)
The synthesis and the biological evaluation of new potent phosphodiesterase type 4 (PDE4) inhibitors are presented. This new series was elaborated by replacement of the metabolically resistant phenyl hexafluorocarbinol of L-791,943 (1) by a substituted aminopyridine residue. The structure-activity relationship of N-substitution on 3 led to the identification of (-)-3n which exhibited a good PDE4 inhibitor activity (HWB-TNFα=0.12 μM) and an improved pharmacokinetic profile over L-791,943 (rat t1/2=2 h). (-)-3n was well tolerated in ferret with an emetic threshold of 30 mg/kg (po) and was found to be active in the ovalbumin-induced bronchoconstriction model in guinea pig (54%, 0.1 mg/kg, ip) as well as the ascaris-induced bronchoconstriction model in sheep (64%/97%, early/late, 0.5 mg/kg, iv).
