Abstract
Novel N-[3-(4-phenylpiperazin-1-yl)-propyl] derivatives of 3-spiro-cyclo-hexanepyrrolidine-2,5-dione (5-7) and 3-spiro-beta-tetralonepyrrolidine-2,5-dione (8-10) were synthesized and their 5-HT1A and 5-HT2A receptor affinities were determined. All tested compounds exhibited moderate to low 5-HT1A receptor affinity, whereas compounds 5-7 demonstrated high 5-HT2A receptor affinity (Ki = 27, 46 and 15 nM, respectively) and features of 5-HT2A receptor antagonists. Introduction of a beta-tetralone fragment in the 3-position of pyrrolidine-2,5-dione ring (8-10) did not affect 5-HT1A but decreased 5-HT2A receptor affinity.
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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Behavior, Animal / drug effects
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Binding, Competitive
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Dose-Response Relationship, Drug
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Male
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Mice
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Models, Molecular
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Molecular Structure
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Pyrrolidines / chemical synthesis
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Pyrrolidines / metabolism*
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Pyrrolidines / pharmacology
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Radioligand Assay
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Receptor, Serotonin, 5-HT1A / metabolism*
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Receptor, Serotonin, 5-HT2A / metabolism*
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Serotonin Agents / chemical synthesis
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Serotonin Agents / metabolism*
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Serotonin Agents / pharmacology
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Spiro Compounds / chemical synthesis
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Spiro Compounds / metabolism*
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Spiro Compounds / pharmacology
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Structure-Activity Relationship
Substances
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3-spiro-beta-tetralonepyrrolidine-2,5-dione
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3-spiro-cyclo-hexanepyrrolidine-2,5-dione
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Pyrrolidines
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Receptor, Serotonin, 5-HT2A
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Serotonin Agents
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Spiro Compounds
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Receptor, Serotonin, 5-HT1A