Discovery of a potential anti-ischemic stroke agent: 3-pentylbenzo[c]thiophen-1(3H)-one.

Abstract

The development of novel antithrombotic agents with strong free radical scavenging activity is of great significance for the treatment of ischemic stroke. In the present study, 3-alkyl/arylalkyl-substituted benzo[c]thiophen-1(3H)-ones (5a-h) were designed and synthesized. The most active compound 5d significantly inhibited the adenosine diphosphate (ADP) induced and arachidonic acid (AA) induced in vitro platelet aggregation, superior to clinically used antiplatelet drug aspirin (ASP) and anti-ischemic stroke drugs 3-n-butylphthalide (NBP) and edaravone (Eda). More importantly, in comparison with both NBP and Eda, 5d exhibited stronger antithrombotic and free radical scavenging activities and better or comparable neuroprotective effects against ischemia/reperfusion (I/R) in rats by ameliorating neurobehavioral function, reducing infarct size and brain-water content, attenuating cerebral damage, and normalizing the levels of oxidative enzymes. Overall, our findings may provide an alternative strategy for the design of novel anti-ischemic stroke agents more potent than drugs like NBP and Eda.

• Authors: Jing Wu, Jingjing Ling, Xuliang Wang, Tingting Li, Jingchao Liu, Yisheng Lai, Hui Ji, Sixun Peng, Jide Tian, Yihua Zhang
• Journal: Journal of medicinal chemistry (J Med Chem) Vol. 55 Issue 16 Pg. 7173-81 (Aug 23 2012) ISSN: 1520-4804 [Electronic] United States
• PMID: 22827516 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 3-pentylbenzo(c)thiophen-1(3H)-one
• Antioxidants
• Fibrinolytic Agents
• Free Radical Scavengers
• Neuroprotective Agents
• Platelet Aggregation Inhibitors
• Thiophenes

Topics

• Animals
• Antioxidants (chemical synthesis, chemistry, pharmacology)
• Brain (drug effects, pathology)
• Brain Edema (drug therapy, metabolism, pathology)
• Brain Infarction (drug therapy, metabolism, pathology)
• Brain Ischemia (drug therapy, metabolism, pathology)
• Fibrinolytic Agents (chemical synthesis, chemistry, pharmacology)
• Free Radical Scavengers (chemical synthesis, chemistry, pharmacology)
• Male
• Neuroprotective Agents (chemical synthesis, chemistry, pharmacology)
• PC12 Cells
• Platelet Aggregation Inhibitors (chemical synthesis, chemistry, pharmacology)
• Rabbits
• Rats
• Rats, Sprague-Dawley
• Reperfusion Injury (drug therapy, metabolism, pathology)
• Stereoisomerism
• Stroke (drug therapy, metabolism, pathology)
• Structure-Activity Relationship
• Thiophenes (chemical synthesis, chemistry, pharmacology)