Synthesis by microwave irradiation and binding properties of novel 5-HT1A receptor ligands

被引:27
作者
Caliendo, G
Fiorino, F
Perissutti, E
Severino, B
Gessi, S
Cattabriga, E
Borea, PA
Santagada, V
机构
[1] Univ Naples Federico II, Dipartimento Chim Farmaceut & Tossicol, I-80131 Naples, Italy
[2] Univ Ferrara, Dipartimento Med Clin Sperimentale, Sez Farmacol, I-44100 Ferrara, Italy
关键词
microwave; serotonin; 5-HT receptors; benzotriazinone;
D O I
10.1016/S0223-5234(01)01287-9
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
This work reports the synthesis by microwave irradiation and the binding tests on the 5-HT1A, 5-HT2A and 5-HT2C receptors of new substituted piperazines in order to identify selective ligands for 5-HT1A subtype receptor. Conventional heating and microwave irradiation of the reactions was compared. Synthesis by microwave irradiation gave the desired compounds in better yields than those obtained by conventional heating. The overall times for the syntheses were considerably reduced. Some resulting active compounds (29 and 39) were characterised by a good selectivity profile for the 5-HT1A subtype receptor. The more active compounds were selected and further evaluated for their binding affinities on D-1, D-2 dopaminergic and alpha(1), alpha(2) adrenergic receptors. The compound with higher affinity and selectivity for the 5-HT1A over all the considered receptors was the 3-{4-[4-(1,2,3,4-tetrahydronaplithyl)-1-piperazinyl]butan}-benzotriazinone (-)29 (5-HT1A K-i = 36 nM, other receptors not active). (C) 2001 Editions scientifiques et medicales Elsevier SAS.
引用
收藏
页码:873 / 886
页数:14
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