Azulene as a biphenyl mimetic in orexin/hypocretin receptor agonists

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

doi:10.1016/j.bmc.2023.117325

Azulene as a biphenyl mimetic in orexin/hypocretin receptor agonists

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

Research output: Contribution to journal › Article › Scientific › peer-review

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.

Original language	English
Article number	117325
Journal	Bioorganic & Medicinal Chemistry
Volume	88-89
Number of pages	9
ISSN	0968-0896
DOIs	https://doi.org/10.1016/j.bmc.2023.117325
Publication status	Published - 6 Jun 2023
MoE publication type	A1 Journal article-refereed

Fields of Science

Agonist
Azulene
Medicinal chemistry
Orexin receptor
Sulfonamides
3111 Biomedicine
1182 Biochemistry, cell and molecular biology
317 Pharmacy

Access to Document

10.1016/j.bmc.2023.117325Licence: CC BY

1-s2.0-S0968089623001736-mainFinal published version, 1.56 MBLicence: CC BY

Viikki Metabolomics Unit (LS-RIA/ Metabo-HiLIFE)
Sipari, N. (Manager)
Faculty of Biological and Environmental Sciences
Facility/equipment: Core Facility

Cite this

@article{c9572f107a1b42fd9f32fe162591a425,

title = "Azulene as a biphenyl mimetic in orexin/hypocretin receptor agonists",

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 = "Agonist, Azulene, Medicinal chemistry, Orexin receptor, Sulfonamides, 3111 Biomedicine, 1182 Biochemistry, cell and molecular biology, 317 Pharmacy",

author = "Leino, {Teppo O.} and Ainoleena Turku and Lauri Urvas and Karuna Adhikari and Jouni Oksanen and Yana Steynen and Jari Yli-Kauhaluoma and Henri Xhaard and Kukkonen, {Jyrki P.} and Wall{\'e}n, {Erik A. A.}",

year = "2023",

month = jun,

day = "6",

doi = "10.1016/j.bmc.2023.117325",

language = "English",

volume = "88-89",

journal = "Bioorganic & Medicinal Chemistry",

issn = "0968-0896",

publisher = "Elsevier Ltd. ",

}

TY - JOUR

T1 - Azulene as a biphenyl mimetic in orexin/hypocretin receptor agonists

AU - Leino, Teppo O.

AU - Turku, Ainoleena

AU - Urvas, Lauri

AU - Adhikari, Karuna

AU - Oksanen, Jouni

AU - Steynen, Yana

AU - Yli-Kauhaluoma, Jari

AU - Xhaard, Henri

AU - Kukkonen, Jyrki P.

AU - Wallén, Erik A. A.

PY - 2023/6/6

Y1 - 2023/6/6

N2 - 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.

AB - 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.

KW - Agonist

KW - Azulene

KW - Medicinal chemistry

KW - Orexin receptor

KW - Sulfonamides

KW - 3111 Biomedicine

KW - 1182 Biochemistry, cell and molecular biology

KW - 317 Pharmacy

U2 - 10.1016/j.bmc.2023.117325

DO - 10.1016/j.bmc.2023.117325

M3 - Article

SN - 0968-0896

VL - 88-89

JO - Bioorganic & Medicinal Chemistry

JF - Bioorganic & Medicinal Chemistry

M1 - 117325

ER -

Azulene as a biphenyl mimetic in orexin/hypocretin receptor agonists

Abstract

Fields of Science

Access to Document

Equipment

Viikki Metabolomics Unit (LS-RIA/ Metabo-HiLIFE)

Cite this