Abstract
Structure-activity relationship studies centered around 3'-substituted (Z)-5-(2'-(thienylmethylidene))1,2-dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-5H-chromeno[3,4-f]quinolines are described. A series of highly potent and efficacious selective glucocorticoid receptor modulators were identified with in vitro activity comparable to dexamethasone. In vivo evaluation of these compounds utilizing a 28 day mouse tumor xenograft model demonstrated efficacy equal to dexamethasone in the reduction of tumor volume.
MeSH terms
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Animals
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Antineoplastic Agents / chemical synthesis*
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Antineoplastic Agents / chemistry
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Antineoplastic Agents / pharmacology
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Benzopyrans / chemical synthesis*
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Benzopyrans / chemistry
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Benzopyrans / pharmacology
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Binding, Competitive
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Dexamethasone / pharmacology
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Humans
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Mice
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Mineralocorticoid Receptor Antagonists
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Models, Molecular
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Multiple Myeloma / drug therapy*
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Multiple Myeloma / pathology
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Quinolines / chemical synthesis*
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Quinolines / chemistry
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Quinolines / pharmacology
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Receptors, Glucocorticoid / agonists
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Receptors, Glucocorticoid / antagonists & inhibitors
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Receptors, Glucocorticoid / drug effects*
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Receptors, Mineralocorticoid / agonists
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Stereoisomerism
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Structure-Activity Relationship
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Xenograft Model Antitumor Assays
Substances
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Antineoplastic Agents
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Benzopyrans
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Mineralocorticoid Receptor Antagonists
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Quinolines
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Receptors, Glucocorticoid
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Receptors, Mineralocorticoid
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Dexamethasone