Starting from a thiazolidin-4-one HTS hit, a novel series of substituted lactams was identified and developed as dual orexin receptor antagonists. In this Letter, we describe our initial efforts towards the improvement of potency and metabolic stability. These investigations delivered optimized lead compounds with CNS drug-like properties suitable for further optimization.
Keywords: CNS drug discovery; G-protein coupled receptors; Metabolic stability; Orexin antagonists; Structure–activity relationship studies.
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