Abstract
The SAR of a series of pyridazinone derived 5-HT(2C) agonists has been explored and resulted in identification of a compound with excellent levels of 5-HT(2C) functional agonism and selectivity over 5-HT(2A) and 5-HT(2B). This compound displayed good in vivo efficacy in pre-clinical models of stress urinary incontinence, despite having physiochemical properties commensurate with impaired CNS penetration.
MeSH terms
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Animals
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Dogs
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Drug Design
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Humans
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Piperazines / chemical synthesis*
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Piperazines / chemistry
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Piperazines / pharmacology
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Pyridazines / chemical synthesis*
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Pyridazines / chemistry
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Pyridazines / pharmacokinetics
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Pyridazines / pharmacology
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Receptor, Serotonin, 5-HT2A / metabolism
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Receptor, Serotonin, 5-HT2B / metabolism
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Receptor, Serotonin, 5-HT2C / metabolism
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Serotonin 5-HT2 Receptor Agonists*
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Serotonin Receptor Agonists / chemical synthesis*
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Serotonin Receptor Agonists / chemistry
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Serotonin Receptor Agonists / pharmacokinetics
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Structure-Activity Relationship
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Urinary Incontinence, Stress / drug therapy
Substances
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Piperazines
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Pyridazines
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Receptor, Serotonin, 5-HT2A
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Receptor, Serotonin, 5-HT2B
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Receptor, Serotonin, 5-HT2C
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Serotonin 5-HT2 Receptor Agonists
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Serotonin Receptor Agonists