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【结 构 式】 
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【药物名称】 【化学名称】3-(2-Deoxy-beta-D-ribofuranosyl)-6-octylthieno[2,3-d]pyrimidin-2(3H)-one 【CA登记号】 【 分 子 式 】C19H28N2O4S 【 分 子 量 】380.51001 |
【开发单位】Cardiff University (Originator), CNRS (Originator), Rega Institute for Medical Research (Originator) 【药理作用】ANTIINFECTIVE THERAPY, Anti-Varicella Zoster Virus Drugs, Antiviral Drugs |
合成路线1
The known 5-decynyl-2'-deoxyuridine (I) was protected as the bis-silyl ether (II) with chlorotrimethylsilane and triethylamine. Treatment of (II) with POCl3 and triazole produced the triazolyl derivative (III). Finally, reaction of (III) with thioacetic acid gave rise to the desired thienopyrimidine.
| 【1】 Brancale, A.; et al.; Bicyclic anti-VZV nucleosides: Thieno analogues retain full antiviral activity. Bioorg Med Chem Lett 2001, 11, 18, 2507. |
| 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) | 42586 | 5-(1-decynyl)-1-[(2R,4S,5R)-4-hydroxy-5-(hydroxymethyl)tetrahydro-2-furanyl]-2,4(1H,3H)-pyrimidinedione | C19H28N2O5 | 详情 | 详情 | |
| (II) | 52280 | 5-(1-decynyl)-1-(4-[(trimethylsilyl)oxy]-5-{[(trimethylsilyl)oxy]methyl}tetrahydro-2-furanyl)-2,4(1H,3H)-pyrimidinedione | C25H44N2O5Si2 | 详情 | 详情 | |
| (III) | 52281 | 5-(1-decynyl)-4-(1H-1,2,4-triazol-1-yl)-1-(4-[(trimethylsilyl)oxy]-5-{[(trimethylsilyl)oxy]methyl}tetrahydro-2-furanyl)-2(1H)-pyrimidinone | C27H45N5O4Si2 | 详情 | 详情 |
合成路线2
In another synthetic route, the starting 3',5'-di-O-acetyl-5-iodo-2'-deoxyuridine (IV) was converted to the corresponding 4-thio derivative (V) upon treatment with P2S5. This was S-methylated with iodomethane and triethylamine to give the 4-methylthio pyrimidinone (VI). Palladium-catalyzed coupling of this 5-iodopyrimidine (VI) with 1-decyne (VII) furnished the 5-decynyl nucleoside (VIII). Removal of the methylthio group with NaSH in DMF gave directly the cyclized thienopyrimidine (IX). The remaining acetate esters were finally hydrolyzed by treatment with a methanolic solution of ammonium hydroxide.
| 【1】 Brancale, A.; et al.; Bicyclic anti-VZV nucleosides: Thieno analogues retain full antiviral activity. Bioorg Med Chem Lett 2001, 11, 18, 2507. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (IV) | 52282 | {3-(acetyloxy)-5-[5-iodo-2,4-dioxo-3,4-dihydro-1(2H)-pyrimidinyl]tetrahydro-2-furanyl}methyl acetate | C13H15IN2O7 | 详情 | 详情 | |
| (V) | 52283 | {3-(acetyloxy)-5-[5-iodo-2-oxo-4-thioxo-3,4-dihydro-1(2H)-pyrimidinyl]tetrahydro-2-furanyl}methyl acetate | C13H15IN2O6S | 详情 | 详情 | |
| (VI) | 52284 | {3-(acetyloxy)-5-[5-iodo-4-(methylsulfanyl)-2-oxo-1(2H)-pyrimidinyl]tetrahydro-2-furanyl}methyl acetate | C14H17IN2O6S | 详情 | 详情 | |
| (VII) | 42585 | 1-decyne | 764-93-2 | C10H18 | 详情 | 详情 |
| (VIII) | 52285 | {3-(acetyloxy)-5-[5-(1-decynyl)-4-(methylsulfanyl)-2-oxo-1(2H)-pyrimidinyl]tetrahydro-2-furanyl}methyl acetate | C24H34N2O6S | 详情 | 详情 | |
| (IX) | 52286 | 2-[(acetyloxy)methyl]-5-[6-octyl-2-oxothieno[2,3-d]pyrimidin-3(2H)-yl]tetrahydro-3-furanyl acetate | C23H32N2O6S | 详情 | 详情 |