Novel multi-functional nitrones for treatment of ischemic stroke

作者：Sun, Yewei; Zhang, Gaoxiao; Zhang, Zaijun; Yu, Pei; Zhong, Haijing; Du, Jing; Wang, Yuqiang^*

来源：Bioorganic & Medicinal Chemistry, 2012, 20(12): 3939-3945.

DOI：10.1016/j.bmc.2012.04.016

• Chemical synthesis
• Antioxidant
• Antiplatelet aggregant
• Ischemic stroke
• Middle cerebral artery occlusion

Ischemic stroke resulting from obstruction of blood vessels is an enormous public health problem with urgent need for effective therapy. The co-administration of thrombolytic/antiplatelet agent and neuroprotective agent improves therapeutic efficacy and agent possessing both thrombolytic/antiplatelet and antiradical activities provides a promising strategy for the treatment of ischemic stroke. We have previously reported a novel compound, namely TBN, possessing both antiplatelet and antiradical activities, showed significant neuroprotective effect in a rat stroke model. We herein report synthesis of a series of new pyrazine derivatives, and evaluation of their biological activities. Their mechanisms of action were also investigated. Among these new derivatives, compound 21, armed with two nitrone moieties, showed the greatest neuroprotective effects in vitro and in vivo. Compound 21 significantly inhibited ADP-induced platelet aggregation. In a

• 出版日期2012-6-15
• 单位暨南大学