Abstract
Several 2-(arylamino)pyrimidine-5-carboxylic acids were designed as novel retinoid X receptor (RXR) antagonists. Compound 6a or 6b alone did not exhibit differentiation-inducing activity toward HL-60 cells and did not affect the activity of a retinoic acid receptor (RAR) agonist, Am80, but did inhibit the synergistic activity of an RXR agonist, PA024 (3), in the presence of Am80. The activity of 6 was ascribed to selective antagonism at the RXR site of RXR-RAR heterodimers.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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2-Naphthylamine / analogs & derivatives*
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2-Naphthylamine / chemical synthesis
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2-Naphthylamine / chemistry
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2-Naphthylamine / pharmacology
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Benzoates / pharmacology
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Carboxylic Acids / chemical synthesis
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Carboxylic Acids / chemistry
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Carboxylic Acids / pharmacology
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Cell Differentiation / drug effects
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Depression, Chemical
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Dimerization
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HL-60 Cells
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Humans
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Pyrimidines / chemical synthesis*
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Pyrimidines / chemistry
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Pyrimidines / pharmacology
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Receptors, Retinoic Acid / antagonists & inhibitors*
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Retinoid X Receptors
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Structure-Activity Relationship
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Tetrahydronaphthalenes / pharmacology
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Transcription Factors / antagonists & inhibitors*
Substances
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Benzoates
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Carboxylic Acids
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PA024 compound
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Pyrimidines
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Receptors, Retinoic Acid
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Retinoid X Receptors
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Tetrahydronaphthalenes
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Transcription Factors
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tamibarotene
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2-Naphthylamine