Structure–activity relationship studies and sleep-promoting activity of novel 1-chloro-5, 6, 7, 8-tetrahydroimidazo [1, 5-a] pyrazine derivatives as dual orexin receptor …

…, A Boller, T Weller, J Gatfield, C Brisbare-Roch…

Index: Sifferlen, Thierry; Koberstein, Ralf; Cottreel, Emmanuelle; Boller, Amandine; Weller, Thomas; Gatfield, John; Brisbare-Roch, Catherine; Jenck, Francois; Boss, Christoph Bioorganic and Medicinal Chemistry Letters, 2013 , vol. 23, # 13 p. 3857 - 3863

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Citation Number: 10

Abstract

Replacement of the dimethoxyphenyl moiety in the core skeleton of almorexant by appropriately substituted imidazoles afforded novel 1-chloro-5, 6, 7, 8-tetrahydroimidazo [1, 5-a] pyrazine derivatives as potent dual orexin receptor antagonists. We describe in this Letter our efforts to further optimize the potency and brain penetration of these derivatives by fine-tuning of the pivotal phenethyl motif, and we comment on the sleep-promoting activity ...