| 摘要: | 在持續開發新型抗血小板凝集化合物的過程中，發現1-苯甲基-2-(5-甲基-2-呋喃基)苯并咪唑 (1) 具有抗血小板活性。化合物1對於collagen、arachidonic acid及U46619所誘發之血小板凝集具有良好的抑制效果，有發展成抗血栓新藥之潛力。所以，以化合物1為先導化合物，設計1-取代的苯甲基-5(或/和6)-取代-2-(5-甲基-2-呋喃基)苯并咪唑一系列化合物(4~18, 20~34, 36~43, 45~52)。再將所合成的化合物進行抗血小板活性評估，結果顯示化合物19, 20, 25, 29, 30, 33, 34, 36, 37, 40, 41在人類富含血小板血漿中，對於U46619(1μM)所誘導之血小板凝集表現出優良的抑制活性。此研究結果可增加對苯并咪唑衍生物結構與活性間關係的認識，期待能開發出更具良好活性的抗血小板藥物。
In continuing study of novel antiplatelet agents, we had found that 1-benzyl-2-(5-methyl-2-furyl) benzimidazole (1) exhibited good antiplatelet activity. Compound 1 showed good inhibitory effect on the platelet aggregation induced by collagen, arachidonic acid, and U46619. Encourage by this result, compound 1 was selected as a lead compound, and a series of 1-substituted benzyl-5(or/and 6) substituted- 2-(5-methyl-2-
furyl)benzimidazoles (4~18, 20~34, 36~43, 45~52) were synthesized. All the synthesized compounds were evaluated for their antiplatelet activities. The result revealed that compounds 19, 20, 25, 29, 30, 33, 34, 36, 37, 40, 41 showed good inhibitory effects on platelet aggregation induced by U46619 (1 μM) in human platelet-rich plasma. This finding will increase our understanding of SAR of benzimidazoles. We hope to identify novel potent antiplatelet agents in our continuing studies. |
