TY - JOUR
T1 - Design and Synthesis of Non-Peptide, Selective Orexin Receptor 2 Agonists
AU - Nagahara, Takashi
AU - Saitoh, Tsuyoshi
AU - Kutsumura, Noriki
AU - Irukayama-Tomobe, Yoko
AU - Ogawa, Yasuhiro
AU - Kuroda, Daisuke
AU - Gouda, Hiroaki
AU - Kumagai, Hidetoshi
AU - Fujii, Hideaki
AU - Yanagisawa, Masashi
AU - Nagase, Hiroshi
N1 - Publisher Copyright:
© 2015 American Chemical Society.
PY - 2015/8/12
Y1 - 2015/8/12
N2 - Orexins are a family of neuropeptides that regulate sleep/wakefulness, acting on two G-protein-coupled receptors, orexin receptors 1 (OX1R) and 2 (OX2R). Genetic and pharmacologic evidence suggests that orexin receptor agonists, especially OX2R agonist, will be useful for mechanistic therapy of the sleep disorder narcolepsy/cataplexy. We herein report the discovery of a potent (EC50 on OX2R is 0.023 μM) and OX2R-selective (OX1R/OX2R EC50 ratio is 70) agonist, 4′-methoxy-N,N-dimethyl-3′-[N-(3-{[2-(3-methylbenzamido)ethyl]amino}phenyl)sulfamoyl]-(1,1′-biphenyl)-3-carboxamide 26.
AB - Orexins are a family of neuropeptides that regulate sleep/wakefulness, acting on two G-protein-coupled receptors, orexin receptors 1 (OX1R) and 2 (OX2R). Genetic and pharmacologic evidence suggests that orexin receptor agonists, especially OX2R agonist, will be useful for mechanistic therapy of the sleep disorder narcolepsy/cataplexy. We herein report the discovery of a potent (EC50 on OX2R is 0.023 μM) and OX2R-selective (OX1R/OX2R EC50 ratio is 70) agonist, 4′-methoxy-N,N-dimethyl-3′-[N-(3-{[2-(3-methylbenzamido)ethyl]amino}phenyl)sulfamoyl]-(1,1′-biphenyl)-3-carboxamide 26.
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U2 - 10.1021/acs.jmedchem.5b00988
DO - 10.1021/acs.jmedchem.5b00988
M3 - Article
C2 - 26267383
AN - SCOPUS:84945332430
SN - 0022-2623
VL - 58
SP - 7931
EP - 7937
JO - Journal of Medicinal Chemistry
JF - Journal of Medicinal Chemistry
IS - 20
ER -