N′,2-Diphenylquinoline-4-carbohydrazide based NK3 receptor antagonists II

Jason M. Elliott, 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

    Research output: Contribution to journalArticlepeer-review

    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 7 mg/kg po; plasma Occ90 0.4 μM) and has good selectivity and excellent PK properties. © 2006 Elsevier Ltd. All rights reserved.
    Original languageEnglish
    Pages (from-to)5752-5756
    Number of pages4
    JournalBioorganic and Medicinal Chemistry Letters
    Volume16
    Issue number22
    DOIs
    Publication statusPublished - 15 Nov 2006

    Keywords

    • N′-2-Diphenylquinoline-4-carbohydrazide
    • NK3
    • Schizophrenia

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