1、FDA 批准他达拉非用于治疗良性前列腺增生作者：admin 信息来源：www 点击数： 196 更新时间：2011-10-27 2011 年 10 月 6 日，美国食品药品管理局（FDA）批准他达拉非(tadalafi ，商品名 Cialis)用于治疗良性前列腺增生(benign prostatic hyperplasia ，BPH)，该疾病表现为前列腺增大。他达拉非于 2003 年被批准用于治疗 ED，在我国也已获准进口，商品名：西力士。BPH 的常见症状包括排尿困难、尿无力、尿急、包括夜间在内的尿频。在两项临床试验中，根据国际前列腺症状分级标准(the International Pros
2、tate Symptom Score ，IPSS)评估 BPH 症状，与安慰剂组患者相比，每天服用一次 5mg 他达拉非的患者 BPH 症状上有显著统计学差异。上述试验基于 IPSS 总分减少的研究结果。在第三项试验中，同时患有 ED 和 BPH 的患者每天服用一次 5mg 他达拉非，与安慰剂组患者相比，患者的 ED 和 BPH 症状均有改善。测定 ED 的改善程度采用国际勃起功能指数（the International Index of Erectile Function）的评级标准。服用硝酸盐类的患者应禁用他达拉非，例如硝酸甘油，因为联合用药可导致血压降低的危险性。也不推荐他达拉非与 受体
3、阻断剂联合用药，因为在联合用药治疗 BPH 方面也没有足够的研究，且也存在血压降低的风险。FDA 批准的其他 8 种用于治疗 BPH 的药物：保列治（非那雄胺）、适尿通（度他雄胺）、Jalyn（度他雄胺附加坦索罗辛）和 受体阻断剂类：高特灵（特拉唑嗪）、可多华（多沙唑嗪）、坦洛新（坦索罗辛）、Uroxatral（阿夫唑嗪）、 Rapaflo（西罗多辛）。Cialis 相当于伟 哥， 一种治疗性 功能障碍的药物。 临床证明，药效可长达36 小时，30 分钟起效。由于 cialis 的药效可延续性，不需要担心几小时内失效。你和你的伴侣可以好好放松并且享受。cialis 的好处：药效长达 36 小时
4、快速见效很管用使你准备好不必就餐而食百万人使用可以在网上买【药物名称】Tadalafil, GF-196960, IC-351, Cialis化学结构式(Chemical Structure):参考文献 No. 27672标题: Tetracyclic derivs., process of preparation and use作者: Daugan, A.C.-M. (Icos Corp.)来源: EP 0740668; JP 1997508113; US 5859006; US 6025494; US 6127542; WO 9519978合成路线图解说明: Cyclization of
5、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 t
6、he chloroacetyl derivative (V), which is finally cyclized with methylamine in methanol.参考文献 No. 32434标题: Use of cGMP-phosphodiesterase inhibitors to treat impotence作者: Daugan, A.C.-M. (Icos Corp.)来源: JP 1999509221; US 6140329; WO 9703675合成路线图解说明: Cyclization of D-tryptophan methyl ester (I) with pip
7、eronal (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
8、is finally cyclized with methylamine in methanol.参考文献 No. 46213标题: Tetracyclic cyclic GMP-specific phosphodiesterase inhibitors, process of preparation and use作者: Gellibert, F.; Daugan, A.C.-M. (Icos Corp.)来源: US 6143746合成路线图解说明: Cyclization of D-tryptophan methyl ester (I) with piperonal (II) by me
9、ans 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 cycliz
10、ed with methylamine in methanol.参考文献 No. 606182标题: IC-351作者: Mart 韓, L.; Sorbera, L.A.; Leeson, P.A.; Casta 馿 r, J.来源: Drugs Fut 2001,26(1),15合成路线图解说明: Cyclization of D-tryptophan methyl ester (I) with piperonal (II) by means of TFA in dichloromethane gives, after separation of the undesired trans-i
11、somer 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.参考文献 No. 757016标题: The discovery of tadalafil:
12、 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.来源: J Med Chem 2003,46(21),4533合成路线
13、图解说明: 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.
