| Literature DB >> 16950617 |
Jason M Elliott1, Robert W Carling, Gary G Chicchi, James Crawforth, Peter H Hutson, A Brian Jones, Sarah Kelly, Rose Marwood, Georgina Meneses-Lorente, Elena Mezzogori, Fraser Murray, Michael Rigby, Inmaculada Royo, Michael G N Russell, Duncan Shaw, Bindi Sohal, Kwei Lan Tsao, Brian Williams.
Abstract
Introduction of selected amine containing side chains into the 3-position of N',2-diphenylquinoline-4-carbohydrazide based NK3 antagonists abolishes unwanted hPXR activation. Introduction of a fluorine at the 8-position is necessary to minimize unwanted hI(Kr) affinity and a piperazine N-tert-butyl group is necessary for metabolic stability. The lead compound (8m) occupies receptors within the CNS following oral dosing (Occ(90) 7 mg/kg po; plasma Occ(90) 0.4 microM) and has good selectivity and excellent PK properties.Entities:
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Year: 2006 PMID： 16950617 DOI： 10.1016/j.bmcl.2006.08.085
Source DB: PubMed Journal: Bioorg Med Chem Lett ISSN： 0960-894X Impact factor: 2.823