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【结 构 式】 
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【药物名称】KNI-1039 【化学名称】3'-Azido-5'-O-[2-[5-[1(S)-[4(R)-(N-tert-Butylcarbamoyl)-5,5-dimethylthiazolidin-3-ylcarbonyl]-2(S)-[2-(2,6-dimethylphenoxy)acetamido]-3-phenylpropoxy]-5-oxopentanamido]acetyl]-3'-deoxythymidine 【CA登记号】 【 分 子 式 】C47H61N9O12S 【 分 子 量 】976.12732 |
【开发单位】Kyoto Pharmaceutical University (Originator), Osaka Medical College (Originator) 【药理作用】AIDS Medicines, Anti-HIV Agents, ANTIINFECTIVE THERAPY, Chemical Delivery Systems, DRUG DELIVERY, Drug Delivery Systems, HIV Protease Inhibitors |
合成路线1
Coupling of AZT (I) with Boc-Gly-OH (II) by means of dicyclohexyl carbodiimide (DCC) in the presence of dimethylaminopyridine (DMAP) in DMF followed by Boc removal by treatment with HCl/dioxane yields AZT ester (III). On the other hand, KNI-727 (IV) is condensed with glutaric anhydride (V) in THF-ether in the presence of dicyclohexylamine (DCHA) to yield the half ester of KNI-727 (VI), which is then condensed with derivative (III) by means of EDC.HCl in DMF in the presence of HOBt to furnish the target compound.
| 【1】 Sano, K.; Kimura, T.; Hamawaki, T.; Matsumoto, H.; Ota, H.; Hayashi, Y.; Kiso, Y.; Goto, T.; "Double-drugs" - a new class of prodrug form of an HIV protease inhibitor conjugated with a reverse transcriptase inhibitor by a spontaneously cleavable linker. Bioorg Med Chem Lett 2000, 10, 11, 1227. |
| 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) | 45465 | 1-[(4S,5S)-4-azido-5-(hydroxymethyl)isoxazolidinyl]-5-methyl-2,4(1H,3H)-pyrimidinedione | C9H12N6O4 | 详情 | 详情 | |
| (II) | 18066 | N-alpha-t-BOC-glycine; 2-[(tert-butoxycarbonyl)amino]acetic acid | 4530-20-5 | C7H13NO4 | 详情 | 详情 |
| (III) | 45466 | [(4S,5S)-4-azido-2-[5-methyl-2,4-dioxo-3,4-dihydro-1(2H)-pyrimidinyl]isoxazolidinyl]methyl 2-aminoacetate | C11H15N7O5 | 详情 | 详情 | |
| (IV) | 45467 | (4R)-N-(tert-butyl)-3-((2S,3S)-3-[[2-(2,6-dimethylphenoxy)acetyl]amino]-2-hydroxy-4-phenylbutanoyl)-5,5-dimethyl-1,3-thiazolidine-4-carboxamide | C30H41N3O5S | 详情 | 详情 | |
| (V) | 15512 | Glutaric Anhydride; dihydro-2H-pyran-2,6(3H)-dione | 108-55-4 | C5H6O3 | 详情 | 详情 |
| (VI) | 45468 | 5-[((1S,2S)-1-([(4R)-4-[(tert-butylamino)carbonyl]-5,5-dimethyl-1,3-thiazolidin-3-yl]carbonyl)-2-[[2-(2,6-dimethylphenoxy)acetyl]amino]-3-phenylpropyl)oxy]-5-oxopentanoic acid | C35H47N3O8S | 详情 | 详情 |