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【结 构 式】 
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【药物名称】DPP-AZT 【化学名称】3'-Azido-3'-deoxy-5'-O-[2,3-bis(hexadecanoyloxy)propoxy(hydroxy)phosphoryl]thymidine 【CA登记号】161106-33-8, 128506-56-9 ((R)-isomer), 167354-90-7 ((S)-isomer), 177084-49-0 (Na salt) 【 分 子 式 】C45H80N5O11P 【 分 子 量 】898.14005 |
【开发单位】University of Georgia (Originator) 【药理作用】AIDS Medicines, Anti-HIV Agents, ANTIINFECTIVE THERAPY, Chemical Delivery Systems, DRUG DELIVERY, Drug Delivery Systems |
合成路线1
The synthesis of the title compound has been reported by two procedures. Coupling of dipalmitoylphosphatidic acid (I) to 3'-azido-3'-deoxythimidine (AZT) (II) was carried out using triisopropylbenzenesulfonyl chloride in pyridine to provide the target phosphate diester.
| 【1】 Hostetler, K.Y.; Felgner, J.; Richman, D.D.; Selleseth, D.W.; Gardner, M.F.; Ellis, M.N.; Felgner, P.L.; Ricci, J.; Sridhar, C.N.; Phosphatidylazidothymidine and phosphatidyl-ddC: Assessment of uptake in mouse lymphoid tissues and antiviral activities in human immunodeficiency virus-infected cells and in rauscher leukemia virus-infected mice. Antimicrob Agents Chemother 1994, 38, 12, 2792. |
合成路线2
3'-azido-3'-deoxythimidine (II) was phosphitylated with phosphorus trichloride in triethyl phosphate to yield the corresponding hydrogen phosphonate (III). Subsequent coupling of (III) with 1,2-dipalmitoylglycerol (IV) by means of pivaloyl chloride in pyridine produced phosphite ester (V), which was finally oxidized to the title phosphate with ethanolic iodine.
| 【1】 Manouilov, K.K.; Fedorov, I.I.; Boudinot, F.D.; White, C.A.; Kotra, L.P.; Schinazi, R.F.; Hong, C.I.; Chu, C.K.; Lymphatic targeting of anti-HIV nucleosides: Distribution of 3'-azido-3'-deoxythymidine (AZT) and 3'-azido-2',3'-dideoxyuridine (AZdU) after administration of dipalmitoylphosphatidyl prodrugs to mice. Antivir Chem Chemother 1995, 6, 4, 230. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (II) | 25317 | 1-[(2R,4S,5S)-4-azido-5-(hydroxymethyl)tetrahydro-2-furanyl]-5-methyl-2,4(1H,3H)-pyrimidinedione | 101703-35-9 | C10H13N5O4 | 详情 | 详情 |
| (III) | 35627 | [(2S,3S,5R)-3-azido-5-[5-methyl-2,4-dioxo-3,4-dihydro-1(2H)-pyrimidinyl]tetrahydro-2-furanyl]methyl hydrogen phosphonate | C10H14N5O6P | 详情 | 详情 | |
| (IV) | 35628 | 2-hydroxy-1-[(palmitoyloxy)methyl]ethyl palmitate | C35H68O5 | 详情 | 详情 | |
| (V) | 35629 | 2-[[([(2S,3S,5R)-3-azido-5-[5-methyl-2,4-dioxo-3,4-dihydro-1(2H)-pyrimidinyl]tetrahydro-2-furanyl]methoxy)(oxo)phosphoranyl]oxy]-1-[(palmitoyloxy)methyl]ethyl palmitate | C45H80N5O10P | 详情 | 详情 |