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【结 构 式】 
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【药物名称】NMI-678-11 【化学名称】2-[2-[2-Methyl-2-(nitrososulfanyl)propylamino]-2-oxoethoxy]acetic acid 4-[2-(dimethylamino)ethoxy]-5-isopropyl-2-methylphenyl ester succinate 【CA登记号】260267-68-3 【 分 子 式 】C26H41N3O10S 【 分 子 量 】587.69477 |
【开发单位】NitroMed (Originator) 【药理作用】RENAL-UROLOGIC DRUGS, Treatment of Erectile Dysfunction, Treatment of Male Sexual Dysfunction, alpha-Adrenoceptor Antagonists, Nitric Oxide Donors |
合成路线1
Condensation of diglycolic anhydride (I) with 1-amino-2-methylpropane-2-thiol (II) afforded amide (III). Subsequent nitrosation of the thiol group of (III) employing tert-butyl nitrite gave the nitrosothio derivative (IV). This was then condensed with 4-[2-(dimethylamino)ethoxy]-2-methyl-5-isopropylphenol (VI), prepared by basic hydrolysis of moxisylyte (V), and the resulting compound was finally converted to the succinate salt.
| 【1】 Earl, R.A.; et al.; Nitrosylated alpha-adrenergic receptor antagonists as potential agents for the treatment of erectile dysfunction. 219th ACS Natl Meet (March 26 2000, San Francisco) 2000, Abst MEDI 239. |
| 【2】 Gaston, R.D.; Saenz de Tejada, I.; Schroeder, J.D.; Shelekhin, T.E.; Garvey, D.S.; Wang, T. (NitroMed Inc.); Nitrosated and nitrosylated alpha-adrenergic receptor antagonists, compsns. and methods of use. WO 0012075 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (I) | 38871 | 1,4-dioxane-2,6-dione | 4480-83-5 | C4H4O4 | 详情 | 详情 |
| (II) | 38872 | 1-amino-2-methyl-2-propanethiol; 2-amino-1,1-dimethylethylhydrosulfide | C4H11NS | 详情 | 详情 | |
| (III) | 38873 | 2-[2-[(2-methyl-2-sulfanylpropyl)amino]-2-oxoethoxy]acetic acid | C8H15NO4S | 详情 | 详情 | |
| (IV) | 38874 | 2-(2-[[2-methyl-2-(nitrososulfanyl)propyl]amino]-2-oxoethoxy)acetic acid | C8H14N2O5S | 详情 | 详情 | |
| (V) | 38875 | 4-[2-(dimethylamino)ethoxy]-5-isopropyl-2-methylphenyl acetate | C16H25NO3 | 详情 | 详情 | |
| (VI) | 38876 | 4-[2-(dimethylamino)ethoxy]-5-isopropyl-2-methylphenol | C14H23NO2 | 详情 | 详情 |