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ID: ALA1134922

Journal: Bioorg Med Chem Lett

Title: Substituted 4-(2,2-diphenylethyl)pyridine-N-oxides as phosphodiesterase-4 inhibitors: SAR study directed toward the improvement of pharmacokinetic parameters.

Authors: Frenette R, Blouin M, Brideau C, Chauret N, Ducharme Y, Friesen RW, Hamel P, Jones TR, Laliberté F, Li C, Masson P, McAuliffe M, Girard Y.

Abstract: 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.

CiteXplore: 12270195

DOI: 10.1016/s0960-894x(02)00615-7