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【结 构 式】 
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【药物名称】TLK-286, TER-286, Telcyta 【化学名称】2(R)-[2-[4(S)-Amino-4-carboxybutyramido]-3-[2(R)-[bis[N,N-bis(2-chloroethyl)amino]phosphoryloxy]ethylsulfonyl]propionamido]-2-phenylacetic acid 【CA登记号】158382-37-7 【 分 子 式 】C26H40Cl4N5O10PS 【 分 子 量 】787.486 |
【开发单位】Telik (Originator), Taiho (Licensee) 【药理作用】Breast Cancer Therapy, Chemical Delivery Systems, Colorectal Cancer Therapy, DRUG DELIVERY, Drug Delivery Systems, Lung Cancer Therapy, Lymphoma Therapy, Non-Hodgkin's Lymphoma Therapy, Non-Small Cell Lung Cancer Therapy, Oncolytic Drugs, Ovarian Cancer Therapy, DNA Alkylating Drugs, Nitrogen Mustards |
合成路线1
The known gamma-glutamyl-(S-benzylcysteinyl)-(R)-(-)-phenylglycine (V) was debenzylated to the corresponding thiol (VI) by means of sodium in liquid ammonia. Subsequent S-alkylation of (VI) with bromide (III) produced thioether (VII), which was finally oxidized to the title sulfone employing peracetic acid.
| 【1】 Lyttle, M.H.; et al.; Glutathione-S-transferase activates novel alkylating agents. J Med Chem 1994, 37, 10, 1501. |
| 【2】 Kauvar, L.; Lyttle, M.H.; Satyam, A. (Telik, Inc.); Glutathione S-transferase-activated cpds.. WO 9509866 . |
| 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) | 46425 | C10H20BrCl4N2O2P | 详情 | 详情 | ||
| (V) | 46426 | (2S)-2-amino-5-[((1R)-1-[(benzylsulfanyl)methyl]-2-[[(R)-carboxy(phenyl)methyl]amino]-2-oxoethyl)amino]-5-oxopentanoic acid | C23H27N3O6S | 详情 | 详情 | |
| (VI) | 46427 | (2S)-2-amino-5-[[(1R)-2-[[(R)-carboxy(phenyl)methyl]amino]-2-oxo-1-(sulfanylmethyl)ethyl]amino]-5-oxopentanoic acid | C16H21N3O6S | 详情 | 详情 | |
| (VII) | 46428 | (10R,15S)-15-amino-4-[bis(2-chloroethyl)amino]-10-([[(R)-carboxy(phenyl)methyl]amino]carbonyl)-1-chloro-3-(2-chloroethyl)-4,12-dioxo-5-oxa-8-thia-3,11-diaza-4lambda(5)-phosphahexadecan-16-oic acid | C26H40Cl4N5O8PS | 详情 | 详情 |
合成路线2
The intermediate N,N,N',N'-tetrakis(2-chloroethyl)phosphorodiamidate (IV) was prepared by an improved procedure consisting of addition of phosphoryl chloride to 2-bromoethanol (I) in the presence of Et3N, followed by in situ treatment of the resulting intermediate (II) with bis(2-chloroethyl)amine (III).
| 【1】 Lyttle, M.H.; et al.; Glutathione-S-transferase activates novel alkylating agents. J Med Chem 1994, 37, 10, 1501. |
| 【2】 Kauvar, L.; Lyttle, M.H.; Satyam, A. (Telik, Inc.); Glutathione S-transferase-activated cpds.. WO 9509866 . |
| 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) | 10059 | Ethylene bromohydrin; 2-Bromo-1-ethanol | 540-51-2 | C2H5BrO | 详情 | 详情 |
| (II) | 13033 | Dichlorophosphoric acid 2-bromoethyl ester | C2H4BrCl2O2P | 详情 | 详情 | |
| (III) | 21583 | 2-chloro-N-(2-chloroethyl)-1-ethanamine; Bis(2-chloroethyl)amine; 1,1'-iminobis(2-chloroethane); N,N-bis(2-chloroethyl)amine | 821-48-7 | C4H9Cl2N | 详情 | 详情 |
| (IV) | 46425 | C10H20BrCl4N2O2P | 详情 | 详情 |