6533b82dfe1ef96bd1290b79

RESEARCH PRODUCT

Azulene as a biphenyl mimetic in orexin/hypocretin receptor agonists

Teppo O. LeinoAinoleena TurkuLauri UrvasKaruna AdhikariJouni OksanenYana SteynenJari Yli-kauhaluomaHenri XhaardJyrki P. KukkonenErik A.a. Wallén

subject

Orexin receptorSulfonamidesazuleneOrganic ChemistryClinical BiochemistryAgonistPharmaceutical ScienceMedicinal chemistryBiochemistrylääkekemia317 Pharmacymedicinal chemistrysulfonamidesDrug DiscoveryatsuleeniMolecular Medicine1182 Biochemistry cell and molecular biologyAzulene3111 BiomedicineagonistMolecular Biologyorexin receptor

description

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. Peer reviewed

yearjournalcountryeditionlanguage
2023-06-06
10.1016/j.bmc.2023.117325http://hdl.handle.net/10138/359559