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ID: ALA1139719
Journal: Bioorg Med Chem Lett
Title: N',2-diphenylquinoline-4-carbohydrazide based NK3 receptor antagonists II.
Authors: Elliott JM, Carling RW, Chicchi GG, Crawforth J, Hutson PH, Jones AB, Kelly S, Marwood R, Meneses-Lorente G, Mezzogori E, Murray F, Rigby M, Royo I, Russell MG, Shaw D, Sohal B, Tsao KL, Williams B.
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.
CiteXplore: 16950617