192767-13-8Relevant articles and documents
Substituted 4-(2,2-Diphenylethyl)pyridine-N-oxides as phosphodiesterase-4 inhibitors: SAR study directed toward the improvement of pharmacokinetic parameters
Frenette, Richard,Blouin, Marc,Brideau, Christine,Chauret, Nathalie,Ducharme, Yves,Friesen, Richard W.,Hamel, Pierre,Jones, Tom R.,Laliberte, France,Li, Chun,Masson, Paul,McAuliffe, Malia,Girard, Yves
, p. 3009 - 3013 (2007/10/03)
A detailed SAR study directed toward the optimization of pharmacokinetic parameters for analogues of L-791,943 is reported. The introduction of a soft metabolic site on this structure permitted the identification of L-826,141 as a potent phosphodiesterase type 4 (PDE4) inhibitor that is well absorbed and that presents a shorter half-life than L-791,943 in a variety of animal species. The efficacy of L-826,141 is also demonstrated in different in vivo models.
Discovery of L-791,943: a potent, selective, non emetic and orally active phosphodiesterase-4 inhibitor.
Guay, Daniel,Hamel, Pierre,Blouin, Marc,Brideau, Christine,Chan, Chi Chung,Chauret, Nathalie,Ducharme, Yves,Huang, Zheng,Girard, Mario,Jones, Tom R,Laliberte, France,Masson, Paul,McAuliffe, Malia,Piechuta, Hanna,Silva, Jose,Young, Robert N,Girard, Yves
, p. 1457 - 1461 (2007/10/03)
Structure-activity relationship studies directed toward improving the potency and metabolic stability of CDP-840 (3) resulted in the discovery of L-791,943 (11n) as a potent (HWB TNF-alpha = 0.67 microM) and orally active phosphodiesterase type 4 (PDE4) inhibitor. This compound, which bears a stable bis-difluoromethoxy catechol and a pendant hexafluorocarbinol, exhibited a long half-life in rat and in squirrel monkey. It is well tolerated in ferret with an emetic threshold greater than 30 mg/kg (po) and was found to be active in the ovalbumin-induced bronchoconstriction model in guinea pig and in the ascaris-induced bronchoconstriction models in sheep and squirrel monkey.