Synthesis and benzodiazepine receptor affinity of pyrazolo[1,5-α]pyrimidine derivatives.: 3.: New 6-(3-thienyl) series as α1 selective ligands

被引：39
作者：
Selleri, S
Bruni, F
Costagli, C
Costanzo, A
Guerrini, G
Ciciani, G
Gratteri, P
Bonaccini, C
Aiello, PM
Besnard, F
Renard, S
Costa, B
Martini, C
机构：
[1] Univ Florence, Dept Pharmaceut Sci, I-50121 Florence, Italy
[2] Univ Florence, Dept Preclin & Clin Pharmacol, I-50139 Florence, Italy
[3] Synthelabo LERS, Dept Mol & Funct Genom, F-92500 Rueil Malmaison, France
[4] Univ Pisa, Dept Psychiat, I-56126 Pisa, Italy
[5] Univ Pisa, Dept Neurobiol, I-56126 Pisa, Italy
[6] Univ Pisa, Dept Pharmacol, I-56126 Pisa, Italy
[7] Univ Pisa, Dept Biotechnol, I-56126 Pisa, Italy
来源：
JOURNAL OF MEDICINAL CHEMISTRY | 2003年 / 46卷 / 02期
关键词：
D O I：
10.1021/jm020999w
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
New 3-aryl-6-(3-thienyl)pyrazolo[1,5-alpha]pyrimidin-7-ones (2a-j) are synthesized and evaluated in vitro on Bz/GABA(A) receptors and on recombinant benzodiazepine receptors (alphaxbeta2/3gamma2; x = 1-3, 5) expressed in HEK293 cells. SAR studies on the new compounds are conducted and molecular modeling is accomplished to better investigate requirements leading to subtype selectivity. Some of the synthesized compounds are tested in vivo to explore their pharmacological effect as a consequence of their high alpha1beta2gamma2 subtype selectivity observed in vitro.
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收藏
页码：310 / 313
页数：4
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