Design and Synthesis of Butylphthalide‐Hydroxycinnamic Acid Hybrid Derivatives as Potential Antiplatelet Agents

Thirty-eight novel butylphthalide-hydroxycinnamic acid hybrid derivatives were designed and synthesized to discover effective antiplatelet agglutination drugs. Among these compounds, 3 o gave the optimal inhibitory activity against AA-induced platelet aggregation in vitro and also exhibited better inhibition than the precursor 3-n-butylphthalide (NBP) against thrombin-induced platelet contraction, carrageenan-induced tail thrombosis, and FeCl₃-induced common carotid artery thrombosis. Further investigations on the anti-ischemic stroke activity revealed that compound 3 o exhibited a remarkable protective effect against ischemic/reperfusion brain injury. The PAMPA-BBB permeability and liver microsomal stability tests indicated that compound 3 o could traverse the blood-brain barrier and possessed favorable metabolic stability. This research provides a new candidate compound for treating and preventing cerebrovascular diseases caused by thrombosis.