Abstract
Vasopressin 1b (V1b) antagonists have been postulated as possible treatments for depression and anxiety. A novel series of potent and selective V1b antagonists has been identified starting from an in-house screen hit. The incorporation of a sulfonamide linker between a tetrahydroisoquinoline core and amino piperidine lead to the identification of a V1b antagonist with similar affinity for human and rat receptors. Further optimization of the right hand portion afforded potent V1b antagonists that possessed moderate to high selectivity over other receptors.
MeSH terms
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Animals
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Antidiuretic Agents / chemical synthesis
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Antidiuretic Agents / chemistry*
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Antidiuretic Agents / pharmacology
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Antidiuretic Hormone Receptor Antagonists*
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Humans
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Quinolines / chemical synthesis
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Quinolines / chemistry*
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Quinolines / pharmacology
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Rats
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Receptors, Oxytocin / antagonists & inhibitors
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Receptors, Oxytocin / metabolism
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Receptors, Vasopressin / 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 / pharmacology
Substances
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Antidiuretic Agents
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Antidiuretic Hormone Receptor Antagonists
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Quinolines
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Receptors, Oxytocin
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Receptors, Vasopressin
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Sulfonamides
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quinoline