A1 Journal article (refereed)
Azulene as a biphenyl mimetic in orexin/hypocretin receptor agonists (2023)

Leino, T. O., Turku, A., Urvas, L., Adhikari, K., Oksanen, J., Steynen, Y., Yli-Kauhaluoma, J., Xhaard, H., Kukkonen, J. P., & Wallén, E. A.A. (2023). Azulene as a biphenyl mimetic in orexin/hypocretin receptor agonists. Bioorganic and Medicinal Chemistry, 88-89, Article 117325. https://doi.org/10.1016/j.bmc.2023.117325

JYU authors or editors

Publication details

All authors or editors: Leino, Teppo O.; Turku, Ainoleena; Urvas, Lauri; Adhikari, Karuna; Oksanen, Jouni; Steynen, Yana; Yli-Kauhaluoma, Jari; Xhaard, Henri; Kukkonen, Jyrki P.; Wallén, Erik A. A.

Journal or series: Bioorganic and Medicinal Chemistry

ISSN: 0968-0896

eISSN: 1464-3391

Publication year: 2023

Publication date: 09/05/2023

Volume: 88-89

Article number: 117325

Publisher: Elsevier BV

Publication country: United Kingdom

Publication language: English

DOI: https://doi.org/10.1016/j.bmc.2023.117325

Publication open access: Openly available

Publication channel open access: Partially open access channel

Publication is parallel published (JYX): https://jyx.jyu.fi/handle/123456789/87187

Abstract

Azulene is a rare ring structure in drugs, and we investigated whether it could be used as a biphenyl mimetic in known orexin receptor agonist Nag 26, which is binding to both orexin receptors OX1 and OX2 with preference towards OX2. The most potent azulene-based compound was identified as an OX1 orexin receptor agonist (pEC50 = 5.79 ± 0.07, maximum response = 81 ± 8% (s.e.m. of five independent experiments) of the maximum response to orexin-A in Ca2+ elevation assay). However, the azulene ring and the biphenyl scaffold are not identical in their spatial shape and electron distribution, and their derivatives may adopt different binding modes in the binding site.

Keywords: azulene; pharmaceutical chemistry

Free keywords: agonist; azulene; medicinal chemistry; orexin receptor; sulfonamides

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Ministry reporting: Yes

VIRTA submission year: 2023

JUFO rating: 1