Abstract
A model series of 5-HT2C antagonists have been prepared by rapid parallel synthesis. These N-substituted phenyl-N'-pyridin-3-yl ureas were found to have a range of 5-HT2C receptor affinities and selectivities over the closely related 5-HT2A receptor. Extrapolation of simple SAR, derived from this set of compounds, to the more active but synthetically more complex 1-(3-pyridylcarbamoyl)indoline series allowed us to target optimal substitution patterns and identify potent and selective 5-HT(2C/2B) antagonists.
MeSH terms
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Animals
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Humans
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In Vitro Techniques
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Kinetics
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Magnetic Resonance Spectroscopy
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Models, Chemical
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Phenylurea Compounds / chemical synthesis
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Phenylurea Compounds / chemistry*
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Phenylurea Compounds / pharmacology*
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Pyridines / chemical synthesis
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Pyridines / chemistry*
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Pyridines / pharmacology*
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Receptor, Serotonin, 5-HT2B
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Receptor, Serotonin, 5-HT2C
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Receptors, Serotonin / drug effects*
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Receptors, Serotonin / metabolism
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Serotonin Antagonists / chemical synthesis
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Serotonin Antagonists / chemistry*
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Serotonin Antagonists / pharmacology*
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Structure-Activity Relationship
Substances
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Phenylurea Compounds
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Pyridines
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Receptor, Serotonin, 5-HT2B
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Receptor, Serotonin, 5-HT2C
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Receptors, Serotonin
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Serotonin Antagonists