N′, 2-Diphenylquinoline-4-carbohydrazide based NK 3 receptor antagonists II

…, R Marwood, G Meneses-Lorente, E Mezzogori…

Index: Elliott, Jason M.; Carling, Robert W.; Chicchi, Gary G.; Crawforth, James; Hutson, Peter H.; Jones, A. Brian; Kelly, Sarah; Marwood, Rose; Meneses-Lorente, Georgina; Mezzogori, Elena; Murray, Fraser; Rigby, Michael; Royo, Inmaculada; Russell, Michael G.N.; Shaw, Duncan; Sohal, Bindi; Tsao, Kwei Lan; Williams, Brian Bioorganic and Medicinal Chemistry Letters, 2006 , vol. 16, # 22 p. 5752 - 5756

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Citation Number: 14

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 hIKr 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 (Occ90 7mg/kg ...