101580-96-5Relevant 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.
Process for the production of nitro derivatives of aromatic compounds
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, (2008/06/13)
Nitroderivates of aromatic compounds which are difficult to nitrate, can readily be obtained by nitration providing that the aromatic compound is treated with nitric acid or another nitrating agent in the presence of aliphatic or cycloaliphatic hydrocarbons monosubstituted or polysubstituted by halogen, the nitro group or an alkyl sulphonyl group, and the nitro derivative formed subsequently isolated.
