Disubstituted piperidines as potent orexin (hypocretin) receptor antagonists

…, CR Bayona, L Lin, MD Cameron, PH McDonald…

Index: Jiang, Rong; Song, Xinyi; Bali, Purva; Smith, Anthony; Bayona, Claudia Ruiz; Lin, Li; Cameron, Michael D.; McDonald, Patricia H.; Kenny, Paul J.; Kamenecka, Theodore M. Bioorganic and Medicinal Chemistry Letters, 2012 , vol. 22, # 12 p. 3890 - 3894

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Citation Number: 7

Abstract

A series of orexin receptor antagonists was synthesized based on a substituted piperidine scaffold. Through traditional medicinal chemistry structure–activity relationships (SAR), installation of various groups at the 3–6-positions of the piperidine led to modest enhancement in receptor selectivity. Compounds were profiled in vivo for plasma and brain levels in order to identify candidates suitable for efficacy in a model of drug addiction.