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ID: ALA1146725

Journal: Bioorg Med Chem Lett

Title: Discovery and SAR of potent, orally available and brain-penetrable 5,6-dihydro-4H-3-thia-1-aza-benzo[e]azulen- and 4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulen derivatives as neuropeptide Y Y5 receptor antagonists.

Authors: Rueeger H, Gerspacher M, Buehlmayer P, Rigollier P, Yamaguchi Y, Schmidlin T, Whitebread S, Nuesslein-Hildesheim B, Nick H, Cricione L.

Abstract: Combination of structural elements from a potent Y5 antagonist (2) with thiazole fragments that exhibit weak Y5 affinities followed by lead optimisation led to the discovery of (5,6-dihydro-4H-3-thia-1-aza-benzo[e]azulen-2-yl)-piperidin-4-ylmethyl-amino and (4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulen-2-yl)-piperidin-4-ylmethyl-amino derivatives. Both classes of compounds are capable of delivering potent and selective orally and centrally bioavailable NPY Y5 receptor antagonists.

CiteXplore: 15109631

DOI: 10.1016/j.bmcl.2004.03.014