The discovery of novel cyclohexylamide CCR2 antagonists

James C. Lanter; Thomas P. Markotan; Xuqing Zhang; Nalin Subasinghe; Fu An Kang; Cuifen Hou; Monica Singer; Evan Opas; Sandra McKenney; Carl Crysler; Dana Johnson; Christopher J. Molloy; Zhihua Sui

doi:10.1016/j.bmcl.2011.09.113

The discovery of novel cyclohexylamide CCR2 antagonists

James C. Lanter, Thomas P. Markotan, Xuqing Zhang, Nalin Subasinghe, Fu An Kang, Cuifen Hou, Monica Singer, Evan Opas, Sandra McKenney, Carl Crysler, Dana Johnson, Christopher J. Molloy, Zhihua Sui

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

8 Scopus citations

Abstract

As a result of further SAR studies on a piperidinyl piperidine scaffold, we report the discovery of compound 44, a potent, orally bioavailable CCR2 antagonist. While having some in vitro hERG activity, this molecule was clean in an in vivo model of QT prolongation. In addition, it showed excellent efficacy when dosed orally in a transgenic murine model of acute inflammation.

Original language	American English
Pages (from-to)	7496-7501
Number of pages	6
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	21
Issue number	24
DOIs	https://doi.org/10.1016/j.bmcl.2011.09.113
State	Published - Dec 15 2011
Externally published	Yes

ASJC Scopus subject areas

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

Keywords

CCR2 Antagonist
MCP-1
hERG

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10.1016/j.bmcl.2011.09.113

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title = "The discovery of novel cyclohexylamide CCR2 antagonists",

abstract = "As a result of further SAR studies on a piperidinyl piperidine scaffold, we report the discovery of compound 44, a potent, orally bioavailable CCR2 antagonist. While having some in vitro hERG activity, this molecule was clean in an in vivo model of QT prolongation. In addition, it showed excellent efficacy when dosed orally in a transgenic murine model of acute inflammation.",

keywords = "CCR2 Antagonist, MCP-1, hERG",

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doi = "10.1016/j.bmcl.2011.09.113",

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AU - Lanter, James C.

AU - Markotan, Thomas P.

AU - Zhang, Xuqing

AU - Subasinghe, Nalin

AU - Kang, Fu An

AU - Hou, Cuifen

AU - Singer, Monica

AU - Opas, Evan

AU - McKenney, Sandra

AU - Crysler, Carl

AU - Johnson, Dana

AU - Molloy, Christopher J.

AU - Sui, Zhihua

PY - 2011/12/15

Y1 - 2011/12/15

N2 - As a result of further SAR studies on a piperidinyl piperidine scaffold, we report the discovery of compound 44, a potent, orally bioavailable CCR2 antagonist. While having some in vitro hERG activity, this molecule was clean in an in vivo model of QT prolongation. In addition, it showed excellent efficacy when dosed orally in a transgenic murine model of acute inflammation.

AB - As a result of further SAR studies on a piperidinyl piperidine scaffold, we report the discovery of compound 44, a potent, orally bioavailable CCR2 antagonist. While having some in vitro hERG activity, this molecule was clean in an in vivo model of QT prolongation. In addition, it showed excellent efficacy when dosed orally in a transgenic murine model of acute inflammation.

KW - CCR2 Antagonist

KW - MCP-1

KW - hERG

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EP - 7501

JO - Bioorganic and Medicinal Chemistry Letters

JF - Bioorganic and Medicinal Chemistry Letters

IS - 24

ER -

The discovery of novel cyclohexylamide CCR2 antagonists

Abstract

ASJC Scopus subject areas

Keywords

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