Abstract
A novel series of benzenesulfonanilide derivatives of 11β-HSD1 inhibitors were identified via modification of the sulfonamide core of the arylsulfonylpiperazine lead structures. The synthesis, in vitro biological evaluation, and structure-activity relationship of these compounds are presented. Optimization of this series rapidly resulted in the discovery of compounds (S)-10 and (S)-23 (11β-HSD1 SPA IC(50)=1.8 and 1.4 nM, respectively).
Copyright © 2012 Elsevier Ltd. All rights reserved.
MeSH terms
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11-beta-Hydroxysteroid Dehydrogenase Type 1 / antagonists & inhibitors*
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11-beta-Hydroxysteroid Dehydrogenase Type 1 / genetics
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11-beta-Hydroxysteroid Dehydrogenase Type 1 / metabolism
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11-beta-Hydroxysteroid Dehydrogenase Type 1 / pharmacology
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Anilides / chemical synthesis
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Anilides / chemistry*
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Aniline Compounds / chemical synthesis
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Aniline Compounds / chemistry*
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Aniline Compounds / pharmacology
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Crystallography, X-Ray
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Drug Evaluation, Preclinical
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Enzyme Activation / drug effects
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Enzyme Inhibitors / chemical synthesis
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Enzyme Inhibitors / chemistry*
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Enzyme Inhibitors / pharmacology
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HEK293 Cells
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Humans
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Molecular Conformation
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Piperazine
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Piperazines / chemical synthesis
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Piperazines / chemistry*
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Piperazines / pharmacology
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Structure-Activity Relationship
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Sulfonamides / chemical synthesis
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Sulfonamides / chemistry*
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Sulfonamides / pharmacology
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Transfection
Substances
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Anilides
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Aniline Compounds
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Enzyme Inhibitors
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Piperazines
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Sulfonamides
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Piperazine
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11-beta-Hydroxysteroid Dehydrogenase Type 1