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.
Rueeger, Heinrich, Gerspacher, Marc, Buehlmayer, Peter, Rigollier, Pascal, Yamaguchi, Yasuchika, Schmidlin, Tibur, Whitebread, Steven, Nuesslein-Hildesheim, Barbara, Nick, Hanspeter and Cricione, Leoluca (2004) 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. Bioorganic & Medicinal Chemistry Letters, 14 (10). pp. 2451-2457. ISSN 0960-894X
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.
Item Type: | Article |
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Additional Information: | author can archive post-print (ie final draft post-refereeing); Publisher's version/PDF cannot be used |
Keywords: | NPY Y5 antagonists; Neuropetide Y receptors |
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Date Deposited: | 14 Dec 2009 13:54 |
Last Modified: | 31 Jan 2013 01:07 |
URI: | https://oak.novartis.com/id/eprint/762 |