Abstract
The synthesis and biological testing of a novel series of nonpeptide vasopressin receptor antagonists, containing a bridged bicyclic nucleus, are reported. Variation of substituents (R(1)-R(3)) in general formula 3, and the configuration of the stereocenter, resulted in potent V(2)-selective (e.g., 5) and balanced dual V(1a)/V(2) (e.g., 10) compounds. Data from receptor binding, cell-based functional, and in vivo assays are presented [corrected]
MeSH terms
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Animals
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Antidiuretic Hormone Receptor Antagonists*
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Antihypertensive Agents / chemical synthesis*
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Antihypertensive Agents / pharmacokinetics
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Antihypertensive Agents / pharmacology*
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Arginine Vasopressin / antagonists & inhibitors
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Arginine Vasopressin / pharmacology
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Benzodiazepines / chemical synthesis
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Benzodiazepines / pharmacology
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Blood Pressure / drug effects
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Bridged Bicyclo Compounds / chemical synthesis*
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Bridged Bicyclo Compounds / pharmacokinetics
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Bridged Bicyclo Compounds / pharmacology*
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Cells, Cultured
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Chromatography, High Pressure Liquid
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Creatinine / urine
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Electrolytes / urine
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Heterocyclic Compounds, Bridged-Ring / chemical synthesis*
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Heterocyclic Compounds, Bridged-Ring / pharmacokinetics
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Heterocyclic Compounds, Bridged-Ring / pharmacology*
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Humans
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Hypertension / chemically induced
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Hypertension / prevention & control
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Male
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Mass Spectrometry
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Molecular Conformation
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Osmolar Concentration
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Rats
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Rats, Sprague-Dawley
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Recombinant Proteins / drug effects
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Stereoisomerism
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Structure-Activity Relationship
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Urodynamics / drug effects
Substances
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Antidiuretic Hormone Receptor Antagonists
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Antihypertensive Agents
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Bridged Bicyclo Compounds
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Electrolytes
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Heterocyclic Compounds, Bridged-Ring
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Recombinant Proteins
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Arginine Vasopressin
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Benzodiazepines
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Creatinine