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

Title: N′,2-Diphenylquinoline-4-carbohydrazide based NK3 receptor antagonists II
Authors: 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
Source: Elliott, J M, Carling, R W, Chicchi, G G, Crawforth, J, Hutson, P H, Jones, A B, Kelly, S, Marwood, R, Meneses-Lorente, G, Mezzogori, E, Murray, F, Rigby, M, Royo, I, Russell, M G N, Shaw, D, Sohal, B, Tsao, K L & Williams, B 2006, 'N′,2-Diphenylquinoline-4-carbohydrazide based NK3 receptor antagonists II', Bioorganic and Medicinal Chemistry Letters, vol. 16, no. 22, pp. 5752-5756. https://doi.org/10.1016/j.bmcl.2006.08.085
Publication Year: 2006
Collection: The University of Manchester: Research Explorer - Publications
Subject Terms: N′-2-Diphenylquinoline-4-carbohydrazide; NK3; Schizophrenia
Description: 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.
Document Type: article in journal/newspaper
Language: English
ISSN: 1464-3405
Relation: info:eu-repo/semantics/altIdentifier/pmid/16950617; info:eu-repo/semantics/altIdentifier/eissn/1464-3405
DOI: 10.1016/j.bmcl.2006.08.085
Availability: https://research.manchester.ac.uk/en/publications/a20b7226-25cd-406b-a241-6a213d98759e; https://doi.org/10.1016/j.bmcl.2006.08.085
Rights: info:eu-repo/semantics/closedAccess
Accession Number: edsbas.FE31FF27
Database: BASE