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研究生:李建寬
研究生(外文):Jian-Kuan Li
論文名稱:1-取代的苯甲基-5(或6或5,6)鹵素取代-2-(5-甲基-2-呋喃基) 苯并咪唑類化合物之合成及抗血小板活性
論文名稱(外文):Synthesis and antiplatelet activities of 1-substituted benzyl-5(or 6 or 5,6 )halo-2-(5-methyl-2-furyl)benzimidazoles
指導教授:連金城連金城引用關係
指導教授(外文):Jin-Cherng Lien
學位類別:碩士
校院名稱:中國醫藥大學
系所名稱:藥物化學研究所碩士班
學門:醫藥衛生學門
學類:藥學學類
論文種類:學術論文
論文出版年:2013
畢業學年度:101
語文別:中文
論文頁數:169
中文關鍵詞:苯并咪唑抗血小板
外文關鍵詞:benzimidazoleantiplatelet
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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或5,6)鹵素取代-2-(5-甲基-2-呋喃基)苯并咪唑一系列化合物 (3-18,19-43)。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4 , 6 , 10 , 11 , 15 , 21 , 22 , 23 , 24 , 25 , 32 , 33 , 34 , 35 , 36 , 37 , 43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 or 5,6)substituted-2-(5-methyl-2-furyl) benzimidazoles derivatives (3-18,19-43) were synthesized in this work.
All the synthesized compounds were evaluated for their antiplatelet activities. The results revealed that compounds 4 , 6 , 10 , 11 , 15 , 21 , 22 , 23 , 24 , 25 , 32 , 33 , 34 , 35 , 36 , 37 , 43 showed good inhibitory effects on platelet aggregation induced by U46619 (1 μM) in human platelet suspension. This finding will increase our understanding of SAR of benzimidazoles. We hope to identify novel potent antiplatelet agents in our continuing studies


圖目錄 III
表目錄 IV
縮寫對照表 V
中文摘要 VI
英文摘要 VII
第一章 緒論 1
第一節 苯并吡唑類化合物之研究概況 1
第二節 苯并吡唑類化合物之合成方法 6
第三節 血小板之生理及病理角色 8
第四節 抗血小板活性藥物之分類 18
第二章 研究動機與目的 21
第三章 結果與討論 28
第一節 化學合成方法 28
第二節 抗血小板活性之測試 34
第四章 結論 41
第五章 實驗部分 41
第一節 試藥來源 43
第二節 重要儀器與實驗材料 45
第三節 各化合物之製備 47
參考文獻 78
圖譜資料 82


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