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Tadalafil, GF-196960, IC-351, Cialis

他达那非Chemical Name: (6R,12aR)-6-(1,3-Benzodioxol-5-yl)-2-methyl-1,2,3,4,6,7,12,12a-octahydropyrazino[1',2':1,6]pyrido[3,4-b]indole-1,4-dione
CAS No. 171596-29-5, 240822-07-5, 171488-03-2 (trans-isomer)
项目整合开发状态: Launched-2003
项目研究机构: GlaxoSmithKline (Originator), Lilly Icos (Marketer), Lilly (Licensee), Lilly Icos (Licensee)
合成路线: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.
📌 参考资料/链接:
参考文献标题:Tetracyclic derivs.,process of preparation and use
文献作者:Daugan,A.C.-M.(Icos Corp.)
参考来源:EP 0740668; JP 1997508113; US 5859006; US 6025494; US 6127542; WO 9519978

📄 详细内容


合成路线: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.

参考文献标题:Use of cGMP-phosphodiesterase inhibitors to treat impotence
文献作者:Daugan,A.C.-M.(Icos Corp.)
参考来源:JP 1999509221; US 6140329; WO 9703675


合成路线: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.

参考文献标题:Tetracyclic cyclic GMP-specific phosphodiesterase inhibitors,process of preparation and use
文献作者:Gellibert,F.; Daugan,A.C.-M.(Icos Corp.)
参考来源:US 6143746


合成路线: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.

参考文献标题:IC-351
文献作者:Mart韓,L.; Sorbera,L.A.; Leeson,P.A.; Castar,J.
参考来源:Drugs Fut 2001,26(1),15


合成路线: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.
参考文献标题:The discovery of tadalafil: A novel and highly selective PDE5 inhibitor.2: 2,3,6,7,12,12a-Hexahydropyrazino[1',2':1,6]pyrido[3,4-b]indole-1,4-dione analogues
文献作者:Daugan,A.; Grondin,P.; Ruault,C.; Le Monnier de Gouville,A.C.; Coste,H.; Linget,J.M.; Kirilovsky,J.; Hyafil,F.; Labaudiniere,R.
参考来源:J Med Chem 2003,46(21),4533


产品链接: CAS No. 171596-29-5››

产品链接: CAS No.171488-03-2››