CIJ-3-2F之新合成法及其活性機轉研究; Investigation on the New Synthetic Strategy and Action Mechanism of CIJ-3-2F

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Title:	CIJ-3-2F之新合成法及其活性機轉研究;Investigation on the New Synthetic Strategy and Action Mechanism of CIJ-3-2F
Authors:	李致寬;Chi-Kuan Li
Contributors:	中國醫藥大學：藥物化學研究所碩士班
Keywords:	烷基化;環化;綠色化學;抗心律不整;血管舒張;akylation;cyclization;green chemistry;antiarrhythmic;vasodilative effect
Date:	2009-07-03
Issue Date:	2009-08-13 09:37:18 (UTC+8)
Abstract:	N-benzyl-furoquinolone具有顯著的抗心律不整活性，為持續提供化合物，以利藥理機轉方面能有更進一步的新發現，著者期望透過新合成方式能使CIJ3-2F及其衍生物得到較高產率，以及降低對環境、人體的傷害。 N-benzyl-furoquinolone舊有合成方法，乃利用有毒化合物DMF為溶媒進行烷基化作用，再利用有毒化物Diphenyl ether為熱媒進行合環作用，DMF及Diphenyl ether在後續處理較為困難且對環境及人體有害；鑒於近來提倡綠色化學，著者欲利用對環境影響較低的ethanol為溶媒進行烷基化反應，再利用Polyphosporic acid為合環催化劑，進行合環作用。 N-benzyl-furoquinolone經研究對抗心律不整有顯著的活性，N-benzyl-furoquinolone利用對於血管具有舒張作用，以達到抗心律不整之作用，N-benzyl-furoquinolone作用於平滑肌細胞時，可藉由促進NO的釋放，活化guanylate cylcase，而產生血管舒張作用；N-benzyl-furoquinolone亦可抑制Ca2+的內流或IP3誘導細胞內Ca2+釋放，與刺激電位依賴型K＋ Channel 開啟，以產生血管舒張。 In order to continuously supply CIJ-3-2F for further investigation on pharmacological mechanism, the author expects for a new synthetic strategy to elevate the yield and lower the damage to environment and human health. The original synthetic method of CIJ-3-2F utilized toxic DMF as solvent to perform alkylation, and toxic diphenyl ether as heat transfer medium to achieve cyclization. The post-treatment process of DMF and Diphenyl ether is more difficult and harmful to human health. According to the recently-advocated green chemistry, the author tries to use ethanol, which produces less effect to environment, as solvent to perform alkylation and polyphosphoric acid to undergo Polyphosphoric acid catalyzed cyclization CIJ-3-2F was proved to possess obvious antiarrhythmic activity. The antiarrhythmic effect of CIJ-3-2F was achieved via vasodilation. While acting on smooth muscle cells, CIJ-3-2F caused vasodilation by inducing the release of NO and activating guanylate cyclase. Besides, The CIJ-3-2F inhibited the influx of Ca2+ as well as IP3-induced intracellular Ca2+ release，stimulated the opening of voltage-dependent K+ channel, and thus produced the vasodilative effect.
Appears in Collections:	[Graduate Institute of Pharmaceutical Chemistry] Theses & dissertations

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