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【结 构 式】 
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【药物名称】NSC-693569 【化学名称】gamma-L-Glutamyl-L-[S-[N-(4-chlorophenyl)-N-hydroxycarbamoyl]]cysteinyl-glycine diethyl ester hydrochloride 【CA登记号】174568-91-3 (free base) 【 分 子 式 】C21H30Cl2N4O8S 【 分 子 量 】569.46525 |
【开发单位】University of Maryland (Originator) 【药理作用】Chemical Delivery Systems, DRUG DELIVERY, Drug Delivery Systems, ONCOLYTIC DRUGS, Glyoxalase I Inhibitors |
合成路线1
Treatment of 4-chlorophenyl chloroformate (I) with N-(4-chlorophenyl) hydroxylamine (II) produced the N-hydroxycarbamate (III). This was condensed with glutathione (IV) to afford thiocarbamate (V). Finally, both carboxylate groups of (V) were esterified in ethanolic HCl to provide the target diethyl ester.
| 【1】 Sentz, D.L.; Kavarana, M.J.; O'Neill, H.B.; Wang, H.; Eiseman, J.L.; Sharkey, E.M.; Creighton, D.J.; Pharmacokinetics and antitumor properties in tumor-bearing mice of an enediol analogue inhibitor of glyoxalase I. Cancer Chemotherapy and Pharmacology 2000, 46, 2, 156. |
| 【2】 Kavarana, M.J.; Kovaleva, E.G.; Creighton, D.J.; Wollman, M.B.; Eiseman, J.L.; Mechanism-based competitive inhibitors of glyoxalase I: Intracellular delivery, in vitro antitumor activities, and stabilities in human serum and mouse serum. J Med Chem 1999, 42, 2, 221. |
| 【3】 Muthy, N.S.R.K.; et al.; S-(N-Aryl-N-hydroxycarbamoyl)glutathione derivatives are tight-binding inhibitors of Glyoxalase I and Slow Substrates for Glyoxalase II. J Med Chem 1994, 37, 14, 2161-2166. |
| 【4】 Creighton, D.J.; Hamilton, D.S. (University of Maryland); Glutathione N-hydroxycarbamoyl thioesters and method of inhibiting neoplastic growth. US 5616563; WO 9600061 . |
| 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) | 17779 | 1-chloro-4-[(chlorocarbonyl)oxy]benzene | 7693-45-0 | C7H4Cl2O2 | 详情 | 详情 |
| (II) | 29435 | 1-chloro-4-(hydroxyamino)benzeneN-(4-chlorophenyl)hydroxylamine | C6H6ClNO | 详情 | 详情 | |
| (III) | 29438 | 4-chlorophenyl 4-chlorophenyl(hydroxy)carbamate | C13H9Cl2NO3 | 详情 | 详情 | |
| (IV) | 29436 | (2S)-2-amino-5-[[(1R)-2-[(carboxymethyl)amino]-2-oxo-1-(sulfanylmethyl)ethyl]amino]-5-oxopentanoic acid | 70-18-8 | C10H17N3O6S | 详情 | 详情 |
| (V) | 29437 | (2S)-2-amino-5-([(1R)-2-[(carboxymethyl)amino]-1-[([[4-chloro(hydroxy)anilino]carbonyl]sulfanyl)methyl]-2-oxoethyl]amino)-5-oxopentanoic acid | C17H21ClN4O8S | 详情 | 详情 |