Azulene as a biphenyl mimetic in orexin/hypocretin receptor agonists
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
Published in
Bioorganic and Medicinal ChemistryAuthors
Date
2023Copyright
© 2023 The Author(s). Published by Elsevier Ltd.
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.
Publisher
Elsevier BVISSN Search the Publication Forum
0968-0896Publication in research information system
https://converis.jyu.fi/converis/portal/detail/Publication/183153867
Metadata
Show full item recordCollections
Related funder(s)
Research Council of FinlandFunding program(s)
Postdoctoral Researcher, AoFAdditional information about funding
T.O.L. acknowledges the Doctoral Program in Drug Research of the University of Helsinki and the Academy of Finland (grant no. 330800); A.T. acknowledges the Finnish Cultural Foundation and the Orion Research Foundation; and J.P.K. acknowledges the Magnus Ehrnrooth Foundation, the Liv & Hälsa Foundation and Finska läkaresällskapet for financial support. Marja Peltola, Santeri Suokas and Maiju K. Rinne are acknowledged for assistance with the experiments. We would like to thank Nina Sipari from Viikki Metabolomics Unit (Helsinki Institute of Life Science, University of Helsinki; Biocenter Finland) for her expertise with the LC-MS analyses. CSC – IT Center for Science is thanked for the computational resources. ...License
Related items
Showing items with similar title or keywords.
-
Synthesis of N‐Monosubstituted Sulfondiimines by Metal‐free Iminations of Sulfiliminium Salts
Passia, Marco T.; Bormann, Niklas; Ward, Jas S.; Rissanen, Kari; Bolm, Carsten (Wiley, 2023)Sulfondiimines are marginalized entities among nitrogencontaining organosulfur compounds, despite offering promising properties for applications in various fields including medicinal and agrochemical. Herein, we present a ... -
Dynamics of the ligand-binding domains of ionotropic glutamate receptors
Postila, Pekka (University of Jyväskylä, 2010) -
Structural Mechanism of N-Methyl-D-Aspartate Receptor Type 1 Partial Agonism
Ylilauri, Mikko; Pentikäinen, Olli (Public Library of Science, 2012)N-methyl-D-aspartate (NMDA) receptors belong to a family of ionotropic glutamate receptors that contribute to the signal transmission in the central nervous system. NMDA receptors are heterotetramers that usually consist ... -
Green synthesis of Tacrine modified Schiff bases as Anti-Alzheimer Agents : an effective strategy validated through In-silico and In-vitro analysis
Presenjit; Chaturvedi, Shubhra; Singh, Akanksha; Sharma, Deepika; Chaudhary, Ritika; Verma, Prachi; Singh, Ankita; Singh, Kaman (Elsevier, 2024)A variety of Tacrine-modified Schiff base analogues were developed via solvent free (green) method and structurally elucidated using 1H-NMR, FTIR and UV-Vis analysis. High product yield was obtained from the synthesised ... -
Ion pair recognition by ditopic crown ether based bis-urea and uranyl salophen receptors
Mäkelä, Toni (University of Jyväskylä, 2016)