Bicyclo[3.1.0]hexyl urea melanin concentrating hormone (MCH) receptor-1 antagonists: Impacting hERG liability via aryl modifications

Mark D. McBriar; Henry Guzik; Sherry Shapiro; Ruo Xu; Jaroslava Paruchova; John W. Clader; Kim O'Neill; Brian Hawes; Steve Sorota; Michael Margulis; Kristal Tucker; Daniel J. Weston; Kathleen Cox

doi:10.1016/j.bmcl.2006.05.069

Bicyclo[3.1.0]hexyl urea melanin concentrating hormone (MCH) receptor-1 antagonists: Impacting hERG liability via aryl modifications

Mark D. McBriar, Henry Guzik, Sherry Shapiro, Ruo Xu, Jaroslava Paruchova, John W. Clader, Kim O'Neill, Brian Hawes, Steve Sorota, Michael Margulis, Kristal Tucker, Daniel J. Weston, Kathleen Cox

Penn State Greater Allegheny

Research output: Contribution to journal › Article › peer-review

18 Scopus citations

Abstract

Herein, we report the discovery of an effective strategy to modulate liabilities related to affinity of previously disclosed bicyclohexane MCHR-1 antagonists for the hERG channel. This paper describes one of several strategies incorporated to limit hERG binding via modifications of a terminal aryl group in an otherwise promising bicyclohexyl urea series.

Original language	English (US)
Pages (from-to)	4262-4265
Number of pages	4
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	16
Issue number	16
DOIs	https://doi.org/10.1016/j.bmcl.2006.05.069
State	Published - Aug 15 2006

All Science Journal Classification (ASJC) codes

Biochemistry
Molecular Medicine
Molecular Biology
Pharmaceutical Science
Drug Discovery
Clinical Biochemistry
Organic Chemistry

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10.1016/j.bmcl.2006.05.069

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McBriar, M. D., Guzik, H., Shapiro, S., Xu, R., Paruchova, J., Clader, J. W., O'Neill, K., Hawes, B., Sorota, S., Margulis, M., Tucker, K., Weston, D. J., & Cox, K. (2006). Bicyclo[3.1.0]hexyl urea melanin concentrating hormone (MCH) receptor-1 antagonists: Impacting hERG liability via aryl modifications. Bioorganic and Medicinal Chemistry Letters, 16(16), 4262-4265. https://doi.org/10.1016/j.bmcl.2006.05.069

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abstract = "Herein, we report the discovery of an effective strategy to modulate liabilities related to affinity of previously disclosed bicyclohexane MCHR-1 antagonists for the hERG channel. This paper describes one of several strategies incorporated to limit hERG binding via modifications of a terminal aryl group in an otherwise promising bicyclohexyl urea series.",

author = "McBriar, {Mark D.} and Henry Guzik and Sherry Shapiro and Ruo Xu and Jaroslava Paruchova and Clader, {John W.} and Kim O'Neill and Brian Hawes and Steve Sorota and Michael Margulis and Kristal Tucker and Weston, {Daniel J.} and Kathleen Cox",

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McBriar, MD, Guzik, H, Shapiro, S, Xu, R, Paruchova, J, Clader, JW, O'Neill, K, Hawes, B, Sorota, S, Margulis, M, Tucker, K, Weston, DJ & Cox, K 2006, 'Bicyclo[3.1.0]hexyl urea melanin concentrating hormone (MCH) receptor-1 antagonists: Impacting hERG liability via aryl modifications', Bioorganic and Medicinal Chemistry Letters, vol. 16, no. 16, pp. 4262-4265. https://doi.org/10.1016/j.bmcl.2006.05.069

TY - JOUR

T1 - Bicyclo[3.1.0]hexyl urea melanin concentrating hormone (MCH) receptor-1 antagonists

T2 - Impacting hERG liability via aryl modifications

AU - McBriar, Mark D.

AU - Guzik, Henry

AU - Shapiro, Sherry

AU - Xu, Ruo

AU - Paruchova, Jaroslava

AU - Clader, John W.

AU - O'Neill, Kim

AU - Hawes, Brian

AU - Sorota, Steve

AU - Margulis, Michael

AU - Tucker, Kristal

AU - Weston, Daniel J.

AU - Cox, Kathleen

PY - 2006/8/15

Y1 - 2006/8/15

N2 - Herein, we report the discovery of an effective strategy to modulate liabilities related to affinity of previously disclosed bicyclohexane MCHR-1 antagonists for the hERG channel. This paper describes one of several strategies incorporated to limit hERG binding via modifications of a terminal aryl group in an otherwise promising bicyclohexyl urea series.

AB - Herein, we report the discovery of an effective strategy to modulate liabilities related to affinity of previously disclosed bicyclohexane MCHR-1 antagonists for the hERG channel. This paper describes one of several strategies incorporated to limit hERG binding via modifications of a terminal aryl group in an otherwise promising bicyclohexyl urea series.

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DO - 10.1016/j.bmcl.2006.05.069

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AN - SCOPUS:33745727150

SN - 0960-894X

VL - 16

SP - 4262

EP - 4265

JO - Bioorganic and Medicinal Chemistry Letters

JF - Bioorganic and Medicinal Chemistry Letters

IS - 16

ER -

Bicyclo[3.1.0]hexyl urea melanin concentrating hormone (MCH) receptor-1 antagonists: Impacting hERG liability via aryl modifications

Abstract

All Science Journal Classification (ASJC) codes

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