Azulene as a biphenyl mimetic in orexin/hypocretin receptor agonists.

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 OX and OX with preference towards OX. The most potent azulene-based compound was identified as an OX orexin receptor agonist (pEC = 5.79 ± 0.