Abstract
Two novel quinazolines (2 and 3) related to both prazosin and its open analogue 1 were synthesized, and their biological profile at alpha 1-adrenoceptor subtypes was assessed by functional assays in rat isolated tissues, namely prostatic vas deferens (alpha 1A), spleen (alpha 1B) and aorta (alpha 1D). Furthermore, the binding profile of 3 was assessed at native alpha 2 and D2 receptors, and cloned human 5-HT1A receptors, in comparison to prazosin, (+)-cyclazosin, 1 and BMY 7383. It turned out that the cystamine-bearing quinazoline 3 (cystazosin) has a reversed affinity profile relative to (+)-cyclazosin owing to a higher affinity for alpha 1D-adrenoceptors and a significantly lower affinity for the alpha 1A and alpha 1B subtypes. Furthermore, in comparison to BMY 7378, cystazosin (3) displays a much better specificity profile since it has lower affinity for D2 and 5-HT1A receptors.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adrenergic alpha-1 Receptor Antagonists*
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Adrenergic alpha-Antagonists / chemical synthesis*
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Adrenergic alpha-Antagonists / chemistry
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Adrenergic alpha-Antagonists / pharmacology
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Animals
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Aorta, Thoracic / drug effects
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Binding, Competitive / drug effects
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Drug Design
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Humans
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In Vitro Techniques
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Male
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Quinazolines / chemical synthesis*
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Quinazolines / chemistry
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Quinazolines / pharmacology
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Quinoxalines / chemical synthesis*
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Quinoxalines / chemistry
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Quinoxalines / pharmacology
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Rats
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Receptors, Adrenergic, alpha-1
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Receptors, Serotonin / metabolism
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Receptors, Serotonin, 5-HT1
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Spleen / drug effects
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Structure-Activity Relationship
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Vas Deferens / drug effects
Substances
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ADRA1D protein, human
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Adra1d protein, rat
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Adrenergic alpha-1 Receptor Antagonists
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Adrenergic alpha-Antagonists
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Quinazolines
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Quinoxalines
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Receptors, Adrenergic, alpha-1
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Receptors, Serotonin
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Receptors, Serotonin, 5-HT1
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cyclazosin