Synthesis, structure-activity relationship studies, and identification of novel 5,6,7,8-tetrahydroimidazo[1,5-a]pyrazine derivatives as dual orexin receptor antagonists. Part 1

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• 作者：Thierry Sifferlen ; Ralf Koberstein ; Emmanuelle Cottreel ; Amandine Boller ; Thomas Weller ; John Gatfield ; Catherine Brisbare-Roch ; Francois Jenck ; Christoph Boss ; ^{christoph.boss@actelion.com}
• 关键词：Orexin receptors ; Neuropeptides ; G-protein-coupled-receptors ; Sleep ; 5 ; 6 ; 7 ; 8-Tetrahydroimidazo[1 ; 5-a]pyrazine
• 刊名：Bioorganic and Medicinal Chemistry Letters
• 出版年：2013
• 出版时间：1 April, 2013
• 年：2013
• 卷：23
• 期：7
• 页码：2212-2216
• 全文大小：579 K

文摘

A novel series of non-peptidic OX₁R/OX₂R orexin receptor antagonists was prepared by heterocyclic replacement of the dimethoxyphenyl moiety contained in the tetrahydroisoquinoline core skeleton of almorexant. Introduction of substituted imidazole moieties delivered potent dual orexin receptor antagonists with nanomolar potency for hOX₁R and hOX₂R suitable for further fine-tuning. The preparation of these novel orexin receptor antagonists and the outcome of preliminary structure-activity relationship studies are described in this communication.