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

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Abstract / Description of output

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 - http://www.scopus.com/inward/record.url?scp=77953284860&partnerID=8YFLogxK

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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