Substituted phenyl triazoles as selective inhibitors of 11β-hydroxysteroid dehydrogenase type 1

Wanying Sun; Milana Maletic; Steven S. Mundt; Kashmira Shah; Hratch Zokian; Kathy Lyons; Sherman T. Waddell; James Balkovec

doi:10.1016/j.bmcl.2011.01.125

Substituted phenyl triazoles as selective inhibitors of 11β-hydroxysteroid dehydrogenase type 1

Wanying Sun
, Milana Maletic
, Steven S. Mundt
, Kashmira Shah
, Hratch Zokian
, Kathy Lyons
, Sherman T. Waddell
, James Balkovec

Center for Discovery and Innovation

Merck

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

16 Scopus citations

Abstract

3-(Phenylcyclobutyl)-1,2,4-triazoles were identified as inhibitors of 11β-Hydroxysteroid Dehydrogenase Type 1 (HSD1). They were shown to be active in the mouse in vivo pharmacodynamic model (PD) for HSD1 but exhibited a potent off-target activation of the Pregnane X Receptor (PXR). SAR studies and synthesis of analogs that led to the discovery of a selective HSD1 inhibitor are described in detail.

Original language	English
Pages (from-to)	2141-2145
Number of pages	5
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	21
Issue number	7
DOIs	https://doi.org/10.1016/j.bmcl.2011.01.125
State	Published - 1 Apr 2011

Keywords

11β-Hydroxysteroid Dehydrogenase Type 1
Metabolic Syndrome
Pregnane X Receptor

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10.1016/j.bmcl.2011.01.125

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title = "Substituted phenyl triazoles as selective inhibitors of 11β-hydroxysteroid dehydrogenase type 1",

abstract = "3-(Phenylcyclobutyl)-1,2,4-triazoles were identified as inhibitors of 11β-Hydroxysteroid Dehydrogenase Type 1 (HSD1). They were shown to be active in the mouse in vivo pharmacodynamic model (PD) for HSD1 but exhibited a potent off-target activation of the Pregnane X Receptor (PXR). SAR studies and synthesis of analogs that led to the discovery of a selective HSD1 inhibitor are described in detail.",

keywords = "11β-Hydroxysteroid Dehydrogenase Type 1, Metabolic Syndrome, Pregnane X Receptor",

author = "Wanying Sun and Milana Maletic and Mundt, \{Steven S.\} and Kashmira Shah and Hratch Zokian and Kathy Lyons and Waddell, \{Sherman T.\} and James Balkovec",

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doi = "10.1016/j.bmcl.2011.01.125",

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T1 - Substituted phenyl triazoles as selective inhibitors of 11β-hydroxysteroid dehydrogenase type 1

AU - Sun, Wanying

AU - Maletic, Milana

AU - Mundt, Steven S.

AU - Shah, Kashmira

AU - Zokian, Hratch

AU - Lyons, Kathy

AU - Waddell, Sherman T.

AU - Balkovec, James

PY - 2011/4/1

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AB - 3-(Phenylcyclobutyl)-1,2,4-triazoles were identified as inhibitors of 11β-Hydroxysteroid Dehydrogenase Type 1 (HSD1). They were shown to be active in the mouse in vivo pharmacodynamic model (PD) for HSD1 but exhibited a potent off-target activation of the Pregnane X Receptor (PXR). SAR studies and synthesis of analogs that led to the discovery of a selective HSD1 inhibitor are described in detail.

KW - 11β-Hydroxysteroid Dehydrogenase Type 1

KW - Metabolic Syndrome

KW - Pregnane X Receptor

UR - https://www.scopus.com/pages/publications/79952490041

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M3 - Article

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AN - SCOPUS:79952490041

SN - 0960-894X

VL - 21

SP - 2141

EP - 2145

JO - Bioorganic and Medicinal Chemistry Letters

JF - Bioorganic and Medicinal Chemistry Letters

IS - 7

ER -

Substituted phenyl triazoles as selective inhibitors of 11β-hydroxysteroid dehydrogenase type 1

Abstract

Keywords

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