Modulation of 11beta-hydroxysteroid dehydrogenase type 1 activity by 1,5-substituted 1H-tetrazoles

Scott P. Webster; Margaret Binnie; Kirsty M. M. McConnell; Karen Sooy; Peter Ward; Michael F. Greaney; Andy Vinter; T. David Pallin; Hazel J. Dyke; Matthew I. A. Gill; Ines Warner; Jonathan R. Seckl; Brian R. Walker

doi:10.1016/j.bmcl.2010.04.055

Modulation of 11beta-hydroxysteroid dehydrogenase type 1 activity by 1,5-substituted 1H-tetrazoles

Scott P. Webster
, Margaret Binnie
, Kirsty M. M. McConnell
, Karen Sooy
, Peter Ward
, Michael F. Greaney
, Andy Vinter
, T. David Pallin
, Hazel J. Dyke
, Matthew I. A. Gill
, Ines Warner
, Jonathan R. Seckl
, Brian R. Walker

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

Abstract

Inhibitors of 11beta-hydroxysteroid dehydrogenase (11beta-HSD1) show promise as drugs to treat metabolic disease and CNS disorders such as cognitive impairment. A series of 1,5-substituted 1H-tetrazole 11beta-HSD1 inhibitors has been discovered and chemically modified. Compounds are selective for 11beta-HSD1 over 11beta-HSD2 and possess good cellular potency in human and murine 11beta-HSD1 assays. A range of in vitro stabilities are observed in human liver microsome assays.

Original language	English
Pages (from-to)	3265-3271
Number of pages	7
Journal	Bioorganic & Medicinal Chemistry Letters
Volume	20
Issue number	11
DOIs	https://doi.org/10.1016/j.bmcl.2010.04.055
Publication status	Published - 1 Jun 2010

Keywords / Materials (for Non-textual outputs)

11β-Hydroxysteroid dehydrogenase type 1
11β-HSD1
Drug discovery
Metabolic syndrome

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10.1016/j.bmcl.2010.04.055

http://www.sciencedirect.com/science/article/pii/S0960894X10005251

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Webster, S. P., Binnie, M., McConnell, K. M. M., Sooy, K., Ward, P., Greaney, M. F., Vinter, A., Pallin, T. D., Dyke, H. J., Gill, M. I. A., Warner, I., Seckl, J. R., & Walker, B. R. (2010). Modulation of 11beta-hydroxysteroid dehydrogenase type 1 activity by 1,5-substituted 1H-tetrazoles. Bioorganic & Medicinal Chemistry Letters, 20(11), 3265-3271. https://doi.org/10.1016/j.bmcl.2010.04.055

@article{d802349e57ea4442bdd37acda0dd83c1,

title = "Modulation of 11beta-hydroxysteroid dehydrogenase type 1 activity by 1,5-substituted 1H-tetrazoles",

abstract = "Inhibitors of 11beta-hydroxysteroid dehydrogenase (11beta-HSD1) show promise as drugs to treat metabolic disease and CNS disorders such as cognitive impairment. A series of 1,5-substituted 1H-tetrazole 11beta-HSD1 inhibitors has been discovered and chemically modified. Compounds are selective for 11beta-HSD1 over 11beta-HSD2 and possess good cellular potency in human and murine 11beta-HSD1 assays. A range of in vitro stabilities are observed in human liver microsome assays.",

keywords = "11β-Hydroxysteroid dehydrogenase type 1 , 11β-HSD1 , Drug discovery , Metabolic syndrome ",

author = "Webster, \{Scott P.\} and Margaret Binnie and McConnell, \{Kirsty M. M.\} and Karen Sooy and Peter Ward and Greaney, \{Michael F.\} and Andy Vinter and Pallin, \{T. David\} and Dyke, \{Hazel J.\} and Gill, \{Matthew I. A.\} and Ines Warner and Seckl, \{Jonathan R.\} and Walker, \{Brian R.\}",

year = "2010",

month = jun,

day = "1",

doi = "10.1016/j.bmcl.2010.04.055",

language = "English",

volume = "20",

pages = "3265--3271",

journal = "Bioorganic \& Medicinal Chemistry Letters",

issn = "0960-894X",

publisher = "Elsevier",

number = "11",

}

Webster, SP, Binnie, M, McConnell, KMM, Sooy, K, Ward, P, Greaney, MF, Vinter, A, Pallin, TD, Dyke, HJ, Gill, MIA, Warner, I, Seckl, JR & Walker, BR 2010, 'Modulation of 11beta-hydroxysteroid dehydrogenase type 1 activity by 1,5-substituted 1H-tetrazoles', Bioorganic & Medicinal Chemistry Letters, vol. 20, no. 11, pp. 3265-3271. https://doi.org/10.1016/j.bmcl.2010.04.055

TY - JOUR

T1 - Modulation of 11beta-hydroxysteroid dehydrogenase type 1 activity by 1,5-substituted 1H-tetrazoles

AU - Webster, Scott P.

AU - Binnie, Margaret

AU - McConnell, Kirsty M. M.

AU - Sooy, Karen

AU - Ward, Peter

AU - Greaney, Michael F.

AU - Vinter, Andy

AU - Pallin, T. David

AU - Dyke, Hazel J.

AU - Gill, Matthew I. A.

AU - Warner, Ines

AU - Seckl, Jonathan R.

AU - Walker, Brian R.

PY - 2010/6/1

Y1 - 2010/6/1

N2 - Inhibitors of 11beta-hydroxysteroid dehydrogenase (11beta-HSD1) show promise as drugs to treat metabolic disease and CNS disorders such as cognitive impairment. A series of 1,5-substituted 1H-tetrazole 11beta-HSD1 inhibitors has been discovered and chemically modified. Compounds are selective for 11beta-HSD1 over 11beta-HSD2 and possess good cellular potency in human and murine 11beta-HSD1 assays. A range of in vitro stabilities are observed in human liver microsome assays.

AB - Inhibitors of 11beta-hydroxysteroid dehydrogenase (11beta-HSD1) show promise as drugs to treat metabolic disease and CNS disorders such as cognitive impairment. A series of 1,5-substituted 1H-tetrazole 11beta-HSD1 inhibitors has been discovered and chemically modified. Compounds are selective for 11beta-HSD1 over 11beta-HSD2 and possess good cellular potency in human and murine 11beta-HSD1 assays. A range of in vitro stabilities are observed in human liver microsome assays.

KW - 11β-Hydroxysteroid dehydrogenase type 1

KW - 11β-HSD1

KW - Drug discovery

KW - Metabolic syndrome

UR - https://www.scopus.com/pages/publications/77953284860

U2 - 10.1016/j.bmcl.2010.04.055

DO - 10.1016/j.bmcl.2010.04.055

M3 - Article

C2 - 20452767

SN - 0960-894X

VL - 20

SP - 3265

EP - 3271

JO - Bioorganic & Medicinal Chemistry Letters

JF - Bioorganic & Medicinal Chemistry Letters

IS - 11

ER -

Modulation of 11beta-hydroxysteroid dehydrogenase type 1 activity by 1,5-substituted 1H-tetrazoles

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Keywords / Materials (for Non-textual outputs)

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