- 1,3-Biarylureas as selective non-peptide antagonists of the orexin-1 receptor
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This communication reports SARs for the first orexin-1 receptor antagonist series of 1-aryl-3-quinolin-4-yl and 1-aryl-3-naphthyridin-4-yl ureas. One of these compounds, 31 (SB-334867), has excellent selectivity for the orexin-1 receptor, blood-brain barrier permeability and shows in vivo activity following ip dosing.
- Porter, Roderick A,Chan, Wai N,Coulton, Steven,Johns, Amanda,Hadley, Michael S,Widdowson, Katherine,Jerman, Jeffrey C,Brough, Stephen J,Coldwell, Martyn,Smart, Darren,Jewitt, Frances,Jeffrey, Phillip,Austin, Nigel
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- Novel Sulfonaminoquinoline Hepcidin Antagonists
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The present invention relates to novel hepcidin antagonists, pharmaceutical compositions comprising them and the use thereof as medicaments for the use in the treatment of iron metabolism disorders, such as, in particular, iron deficiency diseases and anemias, in particular anemias in connection with chronic inflammatory diseases.
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- Hydrolytic instability of the important orexin 1 receptor antagonist SB-334867: Possible confounding effects on in vivo and in vitro studies
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SB-334867 has been an important ligand for the study of the orexin 1 (OX1) receptor due to its high OX1/OX2 selectivity and bioavailability. This ligand however, contains a 2-methylbenzoxazole ring system which is known to undergo hydrolysis, particularly under acidic or basic conditions. The possibility that SB-334867 would be susceptible to significant hydrolysis was evaluated in various formulations and in the solid state. SB-334867 was found to be unstable under conditions commonly employed to prepare stock solutions for in vitro and in vivo studies. In addition, and most alarmingly, the hydrochloride salt of SB-334867 was found to quantitatively decompose to an OX1-inactive product even in the solid state. These findings combine to suggest that studies using SB-334867 (and any other 2-methylbenzoxazole-containing compound) should be performed with great care to avoid the confounding effects of the rapid hydrolytic decomposition of this susceptible structure.
- McElhinny Jr., Charles J.,Lewin, Anita H.,Mascarella, S. Wayne,Runyon, Scott,Brieaddy, Lawrence,Carroll, F. Ivy
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supporting information
p. 6661 - 6664
(2013/01/14)
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- ANTIANXIETY DRUGS AND A METHOD OF SCREENING THE SAME
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An anxiolytic drug of the invention comprises an orexin receptor antagonist, a pharmacologically acceptable salt thereof, or a solvate thereof as an active ingredient. A method for screening a compound having an anxiolytic action of the invention comprises a step of using orexin-A.
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Page/Page column 19
(2008/06/13)
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