| 摘要: | 在持續研發新型抗血小板的藥物過程中，發現3-(5-methyl-2- furyl)-1,5-diphenylpyrazole (I)具有優良的抗血小板活性，機轉為抑制cyclic nucleotide phosphodiesterase 5 (PDE5) (IC50 = 4.21 μM)。基於此結果，以化合物I為先導化合物，合成一系列1,5-substituted diphenyl-3-(5-methyl-2-furyl)pyrazole (4-11, 13-18, 21-26, 28-33, 35-40, 42-47)之相關衍生物。將所合成之化合物進行抗血小板活性評估，結果顯示化合物14, 15, 22, 23在人類富含血小板之血漿中，對於ADP (20 μM)及collagen (10 μg/ml)所誘導之血小板凝集表現出優良的抑制活性。以人類血小板懸浮液測試抗血小板凝集活性，化合物4 (IC50 = 0.28 μM)對於collagen (10 μg/ml)所誘導之血小板凝集抑制作用則優於化合物I (IC50 = 3.1 μM)。期待能開發出活性更佳之抗血小板藥物。
In continuing development of novel aniplatelet agents, we had found that 3-(5-methyl-2-furyl)-1,5-diphenylpyrazole ( I) showed good platelet inhibitory activity. The mechanism is inhibition of cyclic nucleotide phosphodiesterase 5 (IC50 = 4.21 μM). Encouraged by this result, the compound I was selected as a lead compound and a series of 1,5- substituted diphenyl-3-(5-methyl-2-furyl)pyrazole derivatives (4-11, 13-18, 21-26, 28-33, 35-40, 42-47) were synthesized in this work. All the synthesized compounds were evaluated for their antiplatelet activities. The results revealed that compounds 14, 15, 22, 23 showed good inhibitory effects on platelet aggregation induced by ADP (20 μM) and collagen (10 μg/ml) in human platelet-rich plasma. In human platelet suspension, the inhibitory effect of compound 4 (IC50 = 0.28 μM) on platelet aggregation induced by collagen (10 μg/ml) was better than compound I (IC50 = 3.1 μM). The goal of our studies is for the development of novel potent antiplatelet agents. |
