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 Raylone Tucker, Daniel J. Weston, Kathleen Cox

Research output: Contribution to journalArticle

12 Citations (Scopus)

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 languageEnglish (US)
Pages (from-to)4262-4265
Number of pages4
JournalBioorganic and Medicinal Chemistry Letters
Volume16
Issue number16
DOIs
StatePublished - Aug 15 2006

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Urea
melanin-concentrating hormone receptor

All Science Journal Classification (ASJC) codes

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

Cite this

McBriar, Mark D. ; Guzik, Henry ; Shapiro, Sherry ; Xu, Ruo ; Paruchova, Jaroslava ; Clader, John W. ; O'Neill, Kim ; Hawes, Brian ; Sorota, Steve ; Margulis, Michael ; Tucker, Kristal Raylone ; Weston, Daniel J. ; Cox, Kathleen. / Bicyclo[3.1.0]hexyl urea melanin concentrating hormone (MCH) receptor-1 antagonists : Impacting hERG liability via aryl modifications. In: Bioorganic and Medicinal Chemistry Letters. 2006 ; Vol. 16, No. 16. pp. 4262-4265.
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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 Tucker, {Kristal Raylone} 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, KR, 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

Bicyclo[3.1.0]hexyl urea melanin concentrating hormone (MCH) receptor-1 antagonists : Impacting hERG liability via aryl modifications. / McBriar, Mark D.; Guzik, Henry; Shapiro, Sherry; Xu, Ruo; Paruchova, Jaroslava; Clader, John W.; O'Neill, Kim; Hawes, Brian; Sorota, Steve; Margulis, Michael; Tucker, Kristal Raylone; Weston, Daniel J.; Cox, Kathleen.

In: Bioorganic and Medicinal Chemistry Letters, Vol. 16, No. 16, 15.08.2006, p. 4262-4265.

Research output: Contribution to journalArticle

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

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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 Raylone

AU - Weston, Daniel J.

AU - Cox, Kathleen

PY - 2006/8/15

Y1 - 2006/8/15

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