N',2-diphenylquinoline-4-carbohydrazide based NK3 receptor antagonists II.

Abstract Introduction of selected amine containing side chains into the 3-position of N ′,2-diphenylquinoline-4-carbohydrazide based NK 3 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 μM) and has good selectivity and excellent PK properties.