33458-99-0Relevant articles and documents
Identification, optimization, and pharmacology of acylurea GHS-R1a inverse agonists
McCoull, William,Barton, Peter,Brown, Alastair J. H.,Bowker, Suzanne S.,Cameron, Jennifer,Clarke, David S.,Davies, Robert D. M.,Dossetter, Alexander G.,Ertan, Anne,Fenwick, Mark,Green, Clive,Holmes, Jane L.,Martin, Nathaniel,Masters, David,Moore, Jane E.,Newcombe, Nicholas J.,Newton, Claire,Pointon, Helen,Robb, Graeme R.,Sheldon, Christopher,Stokes, Stephen,Morgan, David
supporting information, p. 6128 - 6140 (2014/08/18)
Ghrelin plays a major physiological role in the control of food intake, and inverse agonists of the ghrelin receptor (GHS-R1a) are widely considered to offer utility as antiobesity agents by lowering the set-point for hunger between meals. We identified an acylurea series of ghrelin modulators from high throughput screening and optimized binding affinity through structure-activity relationship studies. Furthermore, we identified specific substructural changes, which switched partial agonist activity to inverse agonist activity, and optimized physicochemical and DMPK properties to afford the non-CNS penetrant inverse agonist 22 (AZ-GHS-22) and the CNS penetrant inverse agonist 38 (AZ-GHS-38). Free feeding efficacy experiments showed that CNS exposure was necessary to obtain reduced food intake in mice, and it was demonstrated using GHS-R1a null and wild-type mice that this effect operates through a mechanism involving GHS-R1a.
DIACYLGLYCEROL ACYLTRANSFERASE INHIBITORS
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Page/Page column 12, (2009/04/24)
Provided herein are compounds of the formula (I): as well as pharmaceutically acceptable salts thereof, wherein the substituents are as those disclosed in the specification. These compounds, and the pharmaceutical compositions containing them, are useful for the treatment of diseases such as, for example, obesity, type II diabetes mellitus and metabolic syndrome.
