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【结 构 式】 
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【药物名称】SNO-Yohimbine, S-Nitrosylated yohimbine, NMI-187 【化学名称】(1R,2S,4aR,13bS,14aS)-13-Acetyl-2-[3-methyl-3-(nitrososulfanyl)butanoyloxy]-1,2,3,4,4a,5,7,8,13,13b,14,14a-dodecahydrobenz[g]indolo[2,3-a]quinolizine-1-carboxylic acid methyl ester 【CA登记号】 【 分 子 式 】C28H35N3O6S 【 分 子 量 】541.67165 |
【开发单位】NitroMed (Originator) 【药理作用】RENAL-UROLOGIC DRUGS, Treatment of Erectile Dysfunction, Treatment of Male Sexual Dysfunction, alpha2-Adrenoceptor Antagonists, Nitric Oxide Donors |
合成路线1
3-Mercapto-3-methylbutyric acid (I) was protected as the tetrahydropyranyl derivative (III) using dihydropyran (II) and HCl. Subsequent treatment of (III) with triphosgene and triethylamine generated the acid anhydride (IV). Condensation of yohimbine (V) with anhydride (IV) in the presence of dimethylaminopyridine provided ester (VI). Further acetylation of (VI) with acetyl chloride in acetic acid gave rise to the N,S-diacetyl compound (VII), which was selectively deacetylated with mercuric trifluoroacetate, yielding thiol (VIII). Finally, reaction of (VIII) with NaNO2 and HCl furnished the corresponding S-nitrosyl derivative.
| 【1】 Saenz de Tejada, I.; Schroeder, J.D.; Carvey, D.S. (NitroMed Inc.); Nitrosated and nitrosylated alpha-adrenergic receptor antagonist cpds., compsns. and their uses. JP 2000505424; WO 9727749 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| 19273 | acetyl chloride | 75-36-5 | C2H3ClO | 详情 | 详情 | |
| (I) | 32947 | 3-methyl-3-sulfanylbutyric acid | C5H10O2S | 详情 | 详情 | |
| (II) | 13684 | 3,4-Dihydro-2H-pyran;2,3-Dihydro-4H-pyran; 5,6-Dihydro-4H-pyran;Dihydropyran | 110-87-2 | C5H8O | 详情 | 详情 |
| (III) | 32948 | 3-methyl-3-(tetrahydro-2H-pyran-2-ylsulfanyl)butyric acid | C10H18O3S | 详情 | 详情 | |
| (IV) | 32949 | 2-methyl-2-(tetrahydro-2H-pyran-2-ylsulfanyl)butyric anhydride | C20H34O5S2 | 详情 | 详情 | |
| (V) | 32950 | methyl (1R,2S,4aR,13bS,14aS)-2-hydroxy-1,2,3,4,4a,5,7,8,13,13b,14,14a-dodecahydroindolo[2',3':3,4]pyrido[1,2-b]isoquinoline-1-carboxylate | 146-48-5 | C21H26N2O3 | 详情 | 详情 |
| (VI) | 32951 | methyl (1R,2S,4aR,13bS,14aS)-2-[[3-methyl-3-(tetrahydro-2H-pyran-2-ylsulfanyl)butanoyl]oxy]-1,2,3,4,4a,5,7,8,13,13b,14,14a-dodecahydroindolo[2',3':3,4]pyrido[1,2-b]isoquinoline-1-carboxylate | C31H42N2O5S | 详情 | 详情 | |
| (VII) | 32952 | methyl (1R,2S,4aR,13bS,14aS)-13-acetyl-2-[[3-(acetylsulfanyl)-3-methylbutanoyl]oxy]-1,2,3,4,4a,5,7,8,13,13b,14,14a-dodecahydroindolo[2',3':3,4]pyrido[1,2-b]isoquinoline-1-carboxylate | C30H38N2O6S | 详情 | 详情 | |
| (VIII) | 32953 | methyl (1R,2S,4aR,13bS,14aS)-13-acetyl-2-[(3-methyl-3-sulfanylbutanoyl)oxy]-1,2,3,4,4a,5,7,8,13,13b,14,14a-dodecahydroindolo[2',3':3,4]pyrido[1,2-b]isoquinoline-1-carboxylate | C28H36N2O5S | 详情 | 详情 |