Synthesis and Biological Evaluation of Amidine, Guanidine, and Thiourea Derivatives of 2-Amino(6-trifluoromethoxy)benzothiazole as Neuroprotective Agents Potentially Useful in Brain Diseases

被引：63

作者：

Anzini, Maurizio ^{[1
,2
]}

Chelini, Alessia ^{[1
,2
]}

Mancini, Alessandra ^{[1
,2
]}

Cappelli, Andrea ^{[1
,2
]}

Frosini, Maria ^{[3
]}

Ricci, Lorenzo ^{[3
]}

Valoti, Massimo ^{[3
]}

Magistretti, Jacopo ^{[4
]}

Castelli, Loretta ^{[4
]}

Giordani, Antonio ^{[5
]}

Makovec, Francesco ^{[5
]}

Vomero, Salvatore ^{[1
,2
]}

机构：

[1] Univ Siena, Dipartimento Farmaco Chim Tecnol, I-53100 Siena, Italy

[2] Univ Siena, European Res Ctr Drug Discovery & Dev, I-53100 Siena, Italy

[3] Univ Siena, Dipartimento Neurosci, Sez Farmacol Fisiol & Tossicol, I-53100 Siena, Italy

[4] Univ Pavia, Sez Fis Gen, Dipartimento Fis, I-27100 Pavia, Italy

[5] Rottapharm SpA, I-20052 Monza, Italy

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2010年 / 53卷 / 02期

关键词：

NITRIC-OXIDE SYNTHASE; AMYOTROPHIC-LATERAL-SCLEROSIS; RILUZOLE; SODIUM; GLUTAMATE; MECHANISMS; CHANNELS; CURRENTS; NEURONS; SLICES;

D O I：

10.1021/jm901375r

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of amidine, thiourea, and guanidine derivatives of 2-amino-6-(trifluoromethoxy)benzothiazole termed 2, 3, and 4, respectively, and structurally related to riluzole, a neuroprotective drug in many animal models of brain disease, have been synthesized. The biological activity of compounds 2a-e, 3a-f, and 4a,b was preliminarily tested by means of an in vitro protocol of ischemia/reperfusion injury. The results demonstrated that 2c and 3a-d significantly attenuated neuronal injury. Selected for testing of their antioxidant properties, compounds 3a-d were shown to be endowed with a direct ROS scavenging activity. Compounds 3b and 3d were also evaluated for their activity on voltage-dependent Na(+) and Ca(2+) currents in neurons from rat piriform cortex. At 50 mu M, compound 3b inhibited the transient Na(+) Current to a much smaller extent than riluzole, whereas 3d was almost completely ineffective.

引用

页码：734 / 744

页数：11

共 42 条

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