| Literature DB >> 15261275 |
Laura C McAtee1, Steven W Sutton, Dale A Rudolph, Xiaobing Li, Leah E Aluisio, Victor K Phuong, Curt A Dvorak, Timothy W Lovenberg, Nicholas I Carruthers, Todd K Jones.
Abstract
Orexins, also termed hypocretins, consist of two neuropeptide agonists (orexin A and B) interacting with two known G-protein coupled receptors (OX(1)R and OX(2)R). In addition to other biological functions, the orexin-2 receptor is thought to be an important modulator of sleep and wakefulness. Herein we describe a series of novel, selective OX(2)R antagonists consisting of substituted 4-phenyl-[1,3]dioxanes. One such antagonist is compound 9, 1-(2,4-dibromo-phenyl)-3-((4S,5S)-2,2-dimethyl-4-phenyl-[1,3]dioxan-5-yl)-urea, which is bound by the OX(2)R with a pK(i) of 8.3, has a pK(b) of 7.9, and is 600-fold selective for the OX(2)R over the OX(1)R.Entities:
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Year: 2004 PMID： 15261275 DOI： 10.1016/j.bmcl.2004.06.032
Source DB: PubMed Journal: Bioorg Med Chem Lett ISSN： 0960-894X Impact factor: 2.823