Abstract
High-throughput screening of 3.87 million compounds delivered a novel series of non-steroidal GR antagonists. Subsequent rounds of optimisation allowed progression from a non-selective ligand with a poor ADMET profile to an orally bioavailable, selective, stable, glucocorticoid receptor antagonist.
Copyright © 2010. Published by Elsevier Ltd.
MeSH terms
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Animals
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Drug Evaluation, Preclinical
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High-Throughput Screening Assays
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Humans
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Hydrocortisone / chemistry
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Microsomes / metabolism
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Rats
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Receptors, Glucocorticoid / antagonists & inhibitors*
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Receptors, Glucocorticoid / metabolism
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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 / pharmacokinetics
Substances
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Receptors, Glucocorticoid
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Sulfonamides
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Hydrocortisone