Short Communication Arylpiperazine Derivatives of 3-propyl- -tetralonohydantoin as New 5-ht1a and 5-ht2a Receptor Ligands
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چکیده
A series of new analogues of 3-[3-(4-arylpiperazinyl)-propyl]-cyclohexane-1’,5-spirohydantoin (2), with aromatic ring fused in amide moiety (4–9) were synthesized and evaluated for affinity at 5-HT and 5-HT 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-HT (9, K = 53 nM) and 5-HT (4, 6, 8 and 9; K = 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-HT antagonists. Additionally, a m-CF derivative (9), behaved like a partial agonist (agonist of preand antagonist of postsynaptic) of 5-HT receptors and may offer a new lead for the development of potential psychotropic agents.
منابع مشابه
New 8-aminoalkyl derivatives of purine-2,6-dione with arylalkyl, allyl or propynyl substituents in position 7, their 5-HT1A, 5-HT2A, and 5-HT7 receptor affinity and pharmacological evaluation.
BACKGROUND Our previous studies in a group of arylpiperazine derivatives of 1,3-dimethyl-3,7-dihydro-purine-2,6-diones, aimed at chemical diversification of the purine-2,6-dione by introduction of hydrophobic substituent in a 7- or 8- position or elongation of the linker length between arylpiperazine and purine core, allowed a selection of potent 5-HT1A, 5-HT2A and 5-HT7 receptor ligands displa...
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BACKGROUND The previous study showed that arylpiperazine can condition affinity to α-adrenoceptors, 5-HT1A/5-HT2A receptors and compounds with arylpiperazine had antidepressant-like effect. The aim of this study was to determine the antidepressant-like activity of new arylpiperazines containing novel 8-alkoxy-purine-2,6-dione fragments. METHODS New 3-chloroarylpiperazinylalkyl analogs of 8-al...
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متن کاملSynthesis and 5-HT1A/5-HT2A receptor activity of new N-[3-(4-phenylpiperazin-1-yl)-propyl] derivatives of 3-spiro-cyclohexanepyrrolidine-2,5-dione and 3-spiro-beta-tetralonepyrrolidine-2,5-dione.
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 an...
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تاریخ انتشار 2001