| 摘要: | 在持續開發新型抗血小板凝集化合物的過程中，結果顯示出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，把化合物1當作先導化合物，設計並合成1-取代的苯甲基-5(或 6)-取代-2-(5-甲基-2-呋喃基)苯并咪唑一系列化合物 (4~19, 21~36, 42~51)。再將化合物經由管柱層析分離後，得到的化合物進行抗血小板活性評估，結果顯示化合物12, 13, 19, 22, 32, 36, 42在人類含血小板懸浮液中，對於U46619 (1 μM)所誘導之血小板凝集表現出優良的抑制活性。此研究結果可能增加對苯并咪唑類衍生物結構與活性間關係的認識，更期待能開發出更具良好活性的抗血小板藥物。
In continuing development of novel aniplatelet agents, we had found that 1-benzyl-2-(5-methyl-2-furyl)benzimidazole (1) showed good platelet inhibitory activity. Compound 1 showed good inhibitory effect on the platelet aggregation induced by collagen, arachidonic acid, and U46619. Encouraged by this result, the compound 1 was selected as a lead compound and a series of 1-substituted benzyl-5(or 6)substituted-2-(5-methyl-2-furyl) benzimidazoles derivatives (4-19, 21-36, 42~51) were synthesized in this work.
All the synthesized compounds were evaluated for their antiplatelet activities. The results revealed that compounds 12, 13, 19, 22, 32, 36, 42 showed good inhibitory effects on platelet aggregation induced by U46619 (1 μM) in human platelet suspension. In human platelet suspension, the inhibitory effect of compound 13 (IC50 = 1.17 μM) on platelet aggregation induced by U46619 (1 μM) was much more better than compound 1 (IC50 = 2.45 μM).
This finding will increase our understanding of SAR of benzimidazoles. We hope to identify novel potent antiplatelet agents in our continuing studies. |
