Abstract
Eleven 4-substituted derivatives of 6-nitroquipazine were synthesized and evaluated for their abilities to displace [3H]citalopram binding to the rat cortical synaptic membranes. Among them, 4-chloro-6-nitroquipazine was shown to possess the highest binding affinity (K(i=)0.03 nM) which was approximately 6 times higher than that of 6-nitroquipazine (K(i)=0.17 nM) itself. In this paper, we describe the syntheses of 4-substituted 6-nitroquipazine derivatives, the results of corresponding biological evaluation and the SAR study.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Binding, Competitive
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Carrier Proteins / metabolism*
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Cerebral Cortex / metabolism
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Citalopram / pharmacokinetics
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Drug Design
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Fluoxetine / pharmacology
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Inhibitory Concentration 50
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Kinetics
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Male
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Membrane Glycoproteins / metabolism*
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Membrane Transport Proteins*
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Models, Structural
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Nerve Tissue Proteins*
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Paroxetine / pharmacology
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Quipazine / analogs & derivatives*
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Quipazine / chemical synthesis*
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Quipazine / metabolism*
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Rats
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Rats, Sprague-Dawley
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Serotonin Antagonists / chemical synthesis*
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Serotonin Antagonists / metabolism*
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Serotonin Plasma Membrane Transport Proteins
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Structure-Activity Relationship
Substances
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Carrier Proteins
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Membrane Glycoproteins
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Membrane Transport Proteins
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Nerve Tissue Proteins
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Serotonin Antagonists
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Serotonin Plasma Membrane Transport Proteins
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Slc6a4 protein, rat
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Fluoxetine
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Citalopram
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Paroxetine
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Quipazine
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6-nitroquipazine