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ID: ALA2375312

Journal: Bioorg Med Chem Lett

Title: Novel and highly potent histamine H3 receptor ligands. Part 3: an alcohol function to improve the pharmacokinetic profile.

Authors: Labeeuw O, Levoin N, Poupardin-Olivier O, Calmels T, Ligneau X, Berrebi-Bertrand I, Robert P, Lecomte JM, Schwartz JC, Capet M.

Abstract: Synthesis and biological evaluation of potent histamine H3 receptor antagonists incorporating a hydroxyl function are described. Compounds in this series exhibited nanomolar binding affinities for human receptor, illustrating a new possible component for the H3 pharmacophore. As demonstrated with compound BP1.4160 (cyclohexanol 19), the introduction of an alcohol function counter-intuitively allowed to reach high in vivo efficiency and favorable pharmacokinetic profile with reduced half-life.

CiteXplore: 23535326

DOI: 10.1016/j.bmcl.2013.02.118