Abstract
A series of new analogues of 3-[3-(4-arylpiperazinyl)-propyl]-cyclo-hexane-1',5-spirohydantoin (2), with aromatic ring fused in amide moiety (4-9) were synthesized and evaluated for affinity at 5-HTIA and 5-HT2A receptors. The influence of the substitution mode in the phenyl ring of phenylpiperazine moiety on the affinity for both receptors has been discussed. The most potent 5-HTIA (9, Ki = 53 nM) and 5-HT2A (4, 6, 8 and 9; Ki = 14-76 nM) ligands were evaluated in in vivo tests. The obtained results indicate that all in vivo tested compounds showed pharmacological profile of 5-HT2A antagonists. Additionally, a m-CF3 derivative (9), behaved like a partial agonist (agonist of pre- and antagonist of postsynaptic) of 5-HTIA receptors and may offer a new lead for the development of potential psychotropic agents.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Body Temperature / drug effects
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Cerebral Cortex / metabolism
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Head Movements / drug effects
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Hippocampus / metabolism
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Hydantoins / chemical synthesis
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Hydantoins / chemistry*
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Hydantoins / pharmacology
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In Vitro Techniques
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Ligands
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Lip / drug effects
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Magnetic Resonance Spectroscopy
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Male
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Mice
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Radioligand Assay
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Rats
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Rats, Wistar
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Receptor, Serotonin, 5-HT2A
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Receptors, Serotonin / metabolism*
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Receptors, Serotonin, 5-HT1
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Serotonin Agents / chemical synthesis
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Serotonin Agents / chemistry*
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Serotonin Agents / pharmacology
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Spiro Compounds / chemical synthesis
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Spiro Compounds / chemistry
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Structure-Activity Relationship
Substances
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7,8-benzo-1,3-diazaspiro-(4,5)-decane-2,4-dione
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Hydantoins
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Ligands
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Receptor, Serotonin, 5-HT2A
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Receptors, Serotonin
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Receptors, Serotonin, 5-HT1
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Serotonin Agents
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Spiro Compounds