Phenylcyclobutyl triazoles as selective inhibitors of 11β-hydroxysteroid dehydrogenase type I

Yuping Zhu; Steven H. Olson; Donald Graham; Gool Patel; Anne Hermanowski-Vosatka; Steven Mundt; Kashmira Shah; Marty Springer; Rolf Thieringer; Samuel Wright; Jianying Xiao; Hratch Zokian; Jasminka Dragovic; James M. Balkovec

doi:10.1016/j.bmcl.2008.04.014

Phenylcyclobutyl triazoles as selective inhibitors of 11β-hydroxysteroid dehydrogenase type I

Yuping Zhu
, Steven H. Olson
, Donald Graham
, Gool Patel
, Anne Hermanowski-Vosatka
, Steven Mundt
, Kashmira Shah
, Marty Springer
, Rolf Thieringer
, Samuel Wright
, Jianying Xiao
, Hratch Zokian
, Jasminka Dragovic
, James M. Balkovec

Center for Discovery and Innovation

Hackensack Meridian School of Medicine

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

Abstract

3-(Phenylcyclobutyl)-1,2,4-triazoles were identified as selective inhibitors of 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1). These were active both in vitro and in an in vivo mouse pharmacodynamic (PD) model. Fluorine substitution of the cyclobutane ring improved the pharmacokinetic profile significantly. The synthesis and structure-activity relationships are presented.

Original language	English
Pages (from-to)	3412-3416
Number of pages	5
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	18
Issue number	11
DOIs	https://doi.org/10.1016/j.bmcl.2008.04.014
State	Published - Jun 1 2008

ASJC Scopus subject areas

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

Keywords

11β-HSD1
Metabolic syndrome
Phenylcyclobutyl triazole

Access to Document

10.1016/j.bmcl.2008.04.014

Cite this

Zhu, Y., Olson, S. H., Graham, D., Patel, G., Hermanowski-Vosatka, A., Mundt, S., Shah, K., Springer, M., Thieringer, R., Wright, S., Xiao, J., Zokian, H., Dragovic, J., & Balkovec, J. M. (2008). Phenylcyclobutyl triazoles as selective inhibitors of 11β-hydroxysteroid dehydrogenase type I. Bioorganic and Medicinal Chemistry Letters, 18(11), 3412-3416. https://doi.org/10.1016/j.bmcl.2008.04.014

@article{b50a5027618e4e84b46d1fed0cfcc513,

title = "Phenylcyclobutyl triazoles as selective inhibitors of 11β-hydroxysteroid dehydrogenase type I",

abstract = "3-(Phenylcyclobutyl)-1,2,4-triazoles were identified as selective inhibitors of 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1). These were active both in vitro and in an in vivo mouse pharmacodynamic (PD) model. Fluorine substitution of the cyclobutane ring improved the pharmacokinetic profile significantly. The synthesis and structure-activity relationships are presented.",

keywords = "11β-HSD1, Metabolic syndrome, Phenylcyclobutyl triazole",

author = "Yuping Zhu and Olson, \{Steven H.\} and Donald Graham and Gool Patel and Anne Hermanowski-Vosatka and Steven Mundt and Kashmira Shah and Marty Springer and Rolf Thieringer and Samuel Wright and Jianying Xiao and Hratch Zokian and Jasminka Dragovic and Balkovec, \{James M.\}",

year = "2008",

month = jun,

day = "1",

doi = "10.1016/j.bmcl.2008.04.014",

language = "English",

volume = "18",

pages = "3412--3416",

journal = "Bioorganic and Medicinal Chemistry Letters",

issn = "0960-894X",

publisher = "Elsevier Ltd",

number = "11",

}

Zhu, Y, Olson, SH, Graham, D, Patel, G, Hermanowski-Vosatka, A, Mundt, S, Shah, K, Springer, M, Thieringer, R, Wright, S, Xiao, J, Zokian, H, Dragovic, J & Balkovec, JM 2008, 'Phenylcyclobutyl triazoles as selective inhibitors of 11β-hydroxysteroid dehydrogenase type I', Bioorganic and Medicinal Chemistry Letters, vol. 18, no. 11, pp. 3412-3416. https://doi.org/10.1016/j.bmcl.2008.04.014

TY - JOUR

T1 - Phenylcyclobutyl triazoles as selective inhibitors of 11β-hydroxysteroid dehydrogenase type I

AU - Zhu, Yuping

AU - Olson, Steven H.

AU - Graham, Donald

AU - Patel, Gool

AU - Hermanowski-Vosatka, Anne

AU - Mundt, Steven

AU - Shah, Kashmira

AU - Springer, Marty

AU - Thieringer, Rolf

AU - Wright, Samuel

AU - Xiao, Jianying

AU - Zokian, Hratch

AU - Dragovic, Jasminka

AU - Balkovec, James M.

PY - 2008/6/1

Y1 - 2008/6/1

N2 - 3-(Phenylcyclobutyl)-1,2,4-triazoles were identified as selective inhibitors of 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1). These were active both in vitro and in an in vivo mouse pharmacodynamic (PD) model. Fluorine substitution of the cyclobutane ring improved the pharmacokinetic profile significantly. The synthesis and structure-activity relationships are presented.

AB - 3-(Phenylcyclobutyl)-1,2,4-triazoles were identified as selective inhibitors of 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1). These were active both in vitro and in an in vivo mouse pharmacodynamic (PD) model. Fluorine substitution of the cyclobutane ring improved the pharmacokinetic profile significantly. The synthesis and structure-activity relationships are presented.

KW - 11β-HSD1

KW - Metabolic syndrome

KW - Phenylcyclobutyl triazole

UR - https://www.scopus.com/pages/publications/44149086641

U2 - 10.1016/j.bmcl.2008.04.014

DO - 10.1016/j.bmcl.2008.04.014

M3 - Article

C2 - 18440812

SN - 0960-894X

VL - 18

SP - 3412

EP - 3416

JO - Bioorganic and Medicinal Chemistry Letters

JF - Bioorganic and Medicinal Chemistry Letters

IS - 11

ER -

Phenylcyclobutyl triazoles as selective inhibitors of 11β-hydroxysteroid dehydrogenase type I

Abstract

ASJC Scopus subject areas

Keywords

Access to Document

Other files and links

Fingerprint

Cite this