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

doi:10.1016/j.bmcl.2006.08.085

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 journal › Article › peer-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 language	English
Pages (from-to)	5752-5756
Number of pages	4
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	16
Issue number	22
DOIs	https://doi.org/10.1016/j.bmcl.2006.08.085
Publication status	Published - 15 Nov 2006

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

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

Access to Document

10.1016/j.bmcl.2006.08.085

Cite this

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, 16(22), 5752-5756. https://doi.org/10.1016/j.bmcl.2006.08.085

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title = "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 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. {\textcopyright} 2006 Elsevier Ltd. All rights reserved.",

keywords = "N′-2-Diphenylquinoline-4-carbohydrazide, NK3, Schizophrenia",

author = "Elliott, \{Jason M.\} and Carling, \{Robert W.\} and Chicchi, \{Gary G.\} and James Crawforth and Hutson, \{Peter H.\} and Jones, \{A. Brian\} and Sarah Kelly and Rose Marwood and Georgina Meneses-Lorente and Elena Mezzogori and Fraser Murray and Michael Rigby and Inmaculada Royo and Russell, \{Michael G N\} and Duncan Shaw and Bindi Sohal and Tsao, \{Kwei Lan\} and Brian Williams",

year = "2006",

month = nov,

day = "15",

doi = "10.1016/j.bmcl.2006.08.085",

language = "English",

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journal = "Bioorganic and Medicinal Chemistry Letters",

issn = "1464-3405",

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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, MGN, Shaw, D, Sohal, B, Tsao, KL & 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

TY - JOUR

T1 - N′,2-Diphenylquinoline-4-carbohydrazide based NK3 receptor antagonists II

AU - Elliott, Jason M.

AU - Carling, Robert W.

AU - Chicchi, Gary G.

AU - Crawforth, James

AU - Hutson, Peter H.

AU - Jones, A. Brian

AU - Kelly, Sarah

AU - Marwood, Rose

AU - Meneses-Lorente, Georgina

AU - Mezzogori, Elena

AU - Murray, Fraser

AU - Rigby, Michael

AU - Royo, Inmaculada

AU - Russell, Michael G N

AU - Shaw, Duncan

AU - Sohal, Bindi

AU - Tsao, Kwei Lan

AU - Williams, Brian

PY - 2006/11/15

Y1 - 2006/11/15

N2 - 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.

AB - 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.

KW - N′-2-Diphenylquinoline-4-carbohydrazide

KW - NK3

KW - Schizophrenia

U2 - 10.1016/j.bmcl.2006.08.085

DO - 10.1016/j.bmcl.2006.08.085

M3 - Article

C2 - 16950617

SN - 1464-3405

VL - 16

SP - 5752

EP - 5756

JO - Bioorganic and Medicinal Chemistry Letters

JF - Bioorganic and Medicinal Chemistry Letters

IS - 22

ER -

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

Abstract

UN SDGs

Keywords

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