Azulene-based compounds for targeting orexin receptors

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http://hdl.handle.net/10138/319069

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Leino , T O , Turku , A , Yli-Kauhaluoma , J T , Kukkonen , J P , Xhaard , H & Wallén , E A A 2018 , ' Azulene-based compounds for targeting orexin receptors ' , European Journal of Medicinal Chemistry , vol. 157 , pp. 88-100 . https://doi.org/10.1016/j.ejmech.2018.07.040

Title: Azulene-based compounds for targeting orexin receptors
Author: Leino, Teppo O.; Turku, Ainoleena; Yli-Kauhaluoma, Jari Tapani; Kukkonen, Jyrki P.; Xhaard, Henri; Wallén, Erik A. A.
Contributor: University of Helsinki, Faculty of Pharmacy
University of Helsinki, Pharmaceutical Design and Discovery group
University of Helsinki, Faculty of Pharmacy
University of Helsinki, Jyrki Kukkonen / Principal Investigator
University of Helsinki, Pharmaceutical Design and Discovery group
University of Helsinki, Faculty of Pharmacy
Date: 2018-09-05
Language: eng
Number of pages: 13
Belongs to series: European Journal of Medicinal Chemistry
ISSN: 0223-5234
URI: http://hdl.handle.net/10138/319069
Abstract: A library of 70 000 synthetically accessible azulene-based compounds was virtually screened at the OX2 receptor. Based on the results, a series of azulene derivatives was synthesized and the binding to and activation of both orexin receptor subtypes were assessed. Two most promising binders were determined to have inhibition constants in the 3-9 mu M range and two other compounds showed weak OX2 receptor agonism. Furthermore, three compounds exhibited a concentration-dependent potentiation of the response to orexin-A at the OX1 but not the OX2 receptors. Altogether this data opens new approaches for further development of antagonists, agonists, and potentiators of orexin response based on the azulene scaffold. (C) 2018 Elsevier Masson SAS. All rights reserved.
Subject: 317 Pharmacy
116 Chemical sciences
Azulene
Orexin receptor
Potentiator
Agonist
Antagonist
Sleep-wake regulation
PROTEIN-COUPLED RECEPTORS
HAMSTER OVARY CELLS
SIGNAL-TRANSDUCTION
CA2+ INFLUX
OX1
DERIVATIVES
INHIBITORS
PEPTIDES
LIGANDS
KINASE
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