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

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• 作者：Olivier Labeeuw ; ^{o.labeeuw@bioprojet.com} ; Nicolas Levoin ; Olivia Poupardin-Olivier ; Thierry Calmels ; Xavier Ligneau ; Isabelle Berrebi-Bertrand ; Philippe Robert ; Jeanne-Marie Lecomte ; Jean-Charles Schwartz ; Marc Capet
• 关键词：VKZMICHNLVMXRJ-UAPYVXQJSA-N
• 刊名：Bioorganic and Medicinal Chemistry Letters
• 出版年：2013
• 出版时间：1 May, 2013
• 年：2013
• 卷：23
• 期：9
• 页码：2548-2554
• 全文大小：2431 K

文摘

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.