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

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",

year = "2006",

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doi = "10.1016/j.bmcl.2006.05.069",

language = "English (US)",

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journal = "Bioorganic and Medicinal Chemistry Letters",

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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.

UR - https://www.scopus.com/pages/publications/33745727150

UR - https://www.scopus.com/pages/publications/33745727150#tab=citedBy

U2 - 10.1016/j.bmcl.2006.05.069

DO - 10.1016/j.bmcl.2006.05.069

M3 - Article

C2 - 16753297

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

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