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【结 构 式】 
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【药物名称】Stampidine, Sampidine, STAMP, d4T-pBPMAP, HI-113 【化学名称】5'-O-[(4-Bromophenoxy)(O-methyl-L-alanino)phosphoryl]-3'-deoxy-2',3'-didehydrothymidine 【CA登记号】217178-62-6 【 分 子 式 】C20H23BrN3O8P 【 分 子 量 】544.29941 |
【开发单位】Parker Hughes Institute (Originator) 【药理作用】AIDS Medicines, Anti-HIV Agents, ANTIINFECTIVE THERAPY, Reverse Transcriptase Inhibitors |
合成路线1
The dehydration of thymidine (I) by known methods (J Med Chem 1989, 32: 461) gives 2,3-anhydrothymidine (II), which is then esterifired with the phosphoryl chloride (III) by means of 1-methylimidazole in THF.
| 【1】 Vig, R.; Venkatachalam, T.K.; Uckun, F.M.; D4T-5'-[p-Bromophenyl methoxyalaninyl phosphate] as a potent and non-toxic anti-human immunodeficiency virus agent. Antivir Chem Chemother 1998, 9, 5, 445. |
| 【2】 Venkatachalam, T.K.; Tai, H.-L.; Vig, R.; Chen, C.-L.; Jan, S.-T.; Uckun, F.M.; Enhancing effects of a mono-bromo substitution at the para position of the phenyl moiety on the metabolism and anti-HIV activity of d4T-phenyl methoxyalaninyl phosphate derivatives. Bioorg Med Chem Lett 1998, 8, 22, 3121. |
| 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) | 12161 | Thymidine; 1-[(2R,4S,5R)-4-Hydroxy-5-(hydroxymethyl)tetrahydro-2-furanyl]-5-methyl-2,4(1H,3H)-pyrimidinedione | 50-89-5 | C10H14N2O5 | 详情 | 详情 |
| (II) | 25323 | 1-[(2R,5S)-5-(hydroxymethyl)-2,5-dihydro-2-furanyl]-5-methyl-2,4(1H,3H)-pyrimidinedione | C10H12N2O4 | 详情 | 详情 | |
| (III) | 25316 | methyl 2-[[(4-bromophenoxy)(chloro)phosphoryl]amino]propanoate | C10H12BrClNO4P | 详情 | 详情 |
合成路线2
The intermediate phosphorochloridate (III) has been obtained as follows: The reaction of 4-bromophenol (IV) with POCl3 and triethylamine in ethyl ether gives the corresponding phosphorodichloridate (V), which is finally condensed with L-alanine methyl ester (VI) by means of triethylamine in dichloromethane.
| 【1】 Uckun, F.M. (Parker Hughes Institute); Aryl phosphate derivatives of d4T having anti-HIV activity. WO 0000501 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (III) | 32793 | methyl (2S)-2-[[(4-bromophenoxy)(chloro)phosphoryl]amino]propanoate | C10H12BrClNO4P | 详情 | 详情 | |
| (IV) | 25313 | 4-bromophenol | 106-41-2 | C6H5BrO | 详情 | 详情 |
| (V) | 25314 | Dichlorophoephoric acid 4-bromophenyl ester | C6H4BrCl2O2P | 详情 | 详情 | |
| (VI) | 20694 | methyl (2S)-2-aminopropanoate | C4H9NO2 | 详情 | 详情 |