FDA批準(zhǔn)他達(dá)拉非用于治療良性前列腺增生作者：admin信息來源：www點(diǎn)擊數(shù)： 196更新時間：2011-10-272011年10月6日，美國食品藥品管理局（FDA）批準(zhǔn)他達(dá)拉非(tadalafi，商品名Cialis)用于治療良性前列腺增生(benign prostatic hyperplasia ，BPH)，該疾病表現(xiàn)為前列腺增大。他達(dá)拉非于2003年被批準(zhǔn)用于治療ED，在我國也已獲準(zhǔn)進(jìn)口，商品名：西力士。BPH的常見癥狀包括排尿困難、尿無力、尿急、包括夜間在內(nèi)的尿頻。在兩項(xiàng)臨床試驗(yàn)中，根據(jù)國際前列腺癥狀分級標(biāo)準(zhǔn)(the International Prostate Symptom Score ，IPSS)評估BPH癥狀，與安慰劑組患者相比，每天服用一次5mg他達(dá)拉非的患者BPH癥狀上有顯著統(tǒng)計(jì)學(xué)差異。上述試驗(yàn)基于IPSS總分減少的研究結(jié)果。在第三項(xiàng)試驗(yàn)中，同時患有ED和BPH的患者每天服用一次5mg他達(dá)拉非，與安慰劑組患者相比，患者的ED和BPH癥狀均有改善。測定ED的改善程度采用國際勃起功能指數(shù)（the International Index of Erectile Function）的評級標(biāo)準(zhǔn)。服用硝酸鹽類的患者應(yīng)禁用他達(dá)拉非，例如硝酸甘油，因?yàn)槁?lián)合用藥可導(dǎo)致血壓降低的危險(xiǎn)性。也不推薦他達(dá)拉非與受體阻斷劑聯(lián)合用藥，因?yàn)樵诼?lián)合用藥治療BPH方面也沒有足夠的研究，且也存在血壓降低的風(fēng)險(xiǎn)。FDA批準(zhǔn)的其他8種用于治療BPH的藥物：保列治（非那雄胺）、適尿通（度他雄胺）、Jalyn（度他雄胺附加坦索羅辛）和受體阻斷劑類：高特靈（特拉唑嗪）、可多華（多沙唑嗪）、坦洛新（坦索羅辛）、Uroxatral（阿夫唑嗪）、Rapaflo（西羅多辛）。Cialis相當(dāng)于偉 哥， 一種治療性 功能障礙的藥物。 臨床證明，藥效可長達(dá)36小時，30分鐘起效。由于cialis的藥效可延續(xù)性，不需要擔(dān)心幾小時內(nèi)失效。你和你的伴侶可以好好放松并且享受。cialis的好處：藥效長達(dá)36小時快速見效很管用使你準(zhǔn)備好不必就餐而食百萬人使用可以在網(wǎng)上買窗體頂端【藥物名稱】Tadalafil, GF-196960, IC-351, Cialis化學(xué)結(jié)構(gòu)式(Chemical Structure):參考文獻(xiàn)No.27672標(biāo)題:Tetracyclic derivs., process of preparation and use作者:Daugan, A.C.-M. (Icos Corp.)來源:EP 0740668; JP 1997508113; US 5859006; US 6025494; US 6127542; WO 9519978合成路線圖解說明: Cyclization of D-tryptophan methyl ester (I) with piperonal (II) by means of TFA in dichloromethane gives, after separation of the undesired trans-isomer by flash chromatography, the (1R,3R-cis)-pyrido-indole derivative (III). The acylation of (III) with chloroacetyl chloride (IV) and NaHCO3 in chloroform yields the chloroacetyl derivative (V), which is finally cyclized with methylamine in methanol.參考文獻(xiàn)No.32434標(biāo)題:Use of cGMP-phosphodiesterase inhibitors to treat impotence作者:Daugan, A.C.-M. (Icos Corp.)來源:JP 1999509221; US 6140329; WO 9703675合成路線圖解說明: Cyclization of D-tryptophan methyl ester (I) with piperonal (II) by means of TFA in dichloromethane gives, after separation of the undesired trans-isomer by flash chromatography, the (1R,3R-cis)-pyrido-indole derivative (III). The acylation of (III) with chloroacetyl chloride (IV) and NaHCO3 in chloroform yields the chloroacetyl derivative (V), which is finally cyclized with methylamine in methanol.參考文獻(xiàn)No.46213標(biāo)題:Tetracyclic cyclic GMP-specific phosphodiesterase inhibitors, process of preparation and use作者:Gellibert, F.; Daugan, A.C.-M. (Icos Corp.)來源:US 6143746合成路線圖解說明: Cyclization of D-tryptophan methyl ester (I) with piperonal (II) by means of TFA in dichloromethane gives, after separation of the undesired trans-isomer by flash chromatography, the (1R,3R-cis)-pyrido-indole derivative (III). The acylation of (III) with chloroacetyl chloride (IV) and NaHCO3 in chloroform yields the chloroacetyl derivative (V), which is finally cyclized with methylamine in methanol.參考文獻(xiàn)No.606182標(biāo)題:IC-351作者:Mart韓, L.; Sorbera, L.A.; Leeson, P.A.; Casta馿r, J.來源:Drugs Fut 2001,26(1),15合成路線圖解說明: Cyclization of D-tryptophan methyl ester (I) with piperonal (II) by means of TFA in dichloromethane gives, after separation of the undesired trans-isomer by flash chromatography, the (1R,3R-cis)-pyrido-indole derivative (III). The acylation of (III) with chloroacetyl chloride (IV) and NaHCO3 in chloroform yields the chloroacetyl derivative (V), which is finally cyclized with methylamine in methanol.參考文獻(xiàn)No.757016標(biāo)題:The discovery of tadalafil: A novel and highly selective PDE5 inhibitor. 2: 2,3,6,7,12,12a-Hexahydropyrazino1,2:1,6pyrido3,4-bindole-1,4-dione analogues作者:Daugan, A.; Grondin, P.; Ruault, C.; Le Monnier de Gouville, A.C.; Coste, H.; Linget, J.M.; Kirilovsky, J.; Hyafil, F.; Labaudiniere, R.來源:J Med Chem 2003,46(21),4533合成路線圖解說明: Cyclization of D-tryptophan methyl ester (I) with piperonal (II) by means of TFA in dichloromethane gives, after separation of the undesired trans-isomer by flash chromatography, the (1R,3R-cis)-pyrido-indole d