New Serotoninergic Ligands Containing Indolic and Methyl Indolic Nuclei: Synthesis and In Vitro Pharmacological Evaluation

被引:1
作者
Magli, Elisa [1 ]
Severino, Beatrice [1 ]
Corvino, Angela [1 ]
Perissutti, Elisa [1 ]
Frecentese, Francesco [1 ]
Saccone, Irene [1 ]
Giordano, Flavia [1 ]
Castro, Marian [2 ]
Brea, Jose [2 ]
Loza, Maria I. [2 ]
Santagada, Vincenzo [1 ]
Caliendo, Giuseppe [1 ]
Fiorino, Ferdinando [1 ]
机构
[1] Univ Napoli Federico II, Dipartimento Farm, Via D Montesano 49, I-80131 Naples, Italy
[2] Univ Santiago de Compostela, USEF Screening Platform BioFarma Res Grp, Ctr Res Mol Med & Chron Dis, Santiago De Compostela 15782, Spain
关键词
Arylpiperazine derivatives; binding assay; indolic and methyl indolic nuclei; synthesis; serotonin; 5-HT1A; 5-HT2A and 5-HT2C receptor ligands; 5-HT1A RECEPTOR LIGANDS; ARYLPIPERAZINE DERIVATIVES; 5-HYDROXYTRYPTAMINE(1A); SERIES;
D O I
10.2174/1573406415666190613153220
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
Background: Serotonin is an important biogenic amine and is implicated in wide-ranging physiological and physiopathological processes. Pharmacological manipulation of the serotoninergic system is believed to have a great therapeutic potential. Objectives: In order to identify selective ligands for 5-HT1A, 5-HT2A and 5-HT2C receptors two series of 4-substituted piperazine derivatives, bearing indolic or methyl indolic nuclei, were synthesized. Methods: All the compounds, synthesized by standard solution methods, were evaluated for 5-HT1A, 5-HT2A and 5-HT2C receptors. The highest affine and selective compounds have been evaluated also on dopaminergic (D-1 and D-2) and adrenergic (alpha(1A) and alpha(2A)) receptors. Results: Several of the newly synthesized molecules showed affinity in the nanomolar range for 5-HT1A, 5-HT2A and 5-HT2C receptors and moderate to no affinity for other relevant receptors (D-1, D-2, alpha(1A) and alpha(2A)). Conclusion: Compounds 7f and 10a showed a nanomolar affinity towards 5-HT1A with an in vitro pharmacologic profile compatible with antipsychotic drugs.
引用
收藏
页码:517 / 530
页数:14
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