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【结 构 式】 
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【药物名称】CMDA 【化学名称】4-[N-(2-Chloroethyl)-N-[2-(mesyloxy)ethyl]amino]benzoyl-L-glutamic acid 【CA登记号】122665-73-0 【 分 子 式 】C17H23ClN2O8S 【 分 子 量 】450.89846 |
【开发单位】Institute of Cancer Research (Originator) 【药理作用】Chemical Delivery Systems, DRUG DELIVERY, Drug Delivery Systems, ONCOLYTIC DRUGS, DNA-Damaging Drugs |
合成路线1
The synthesis of CMDA (VII) was accomplished using a modified version of the published procedures: The di-tert-butyl 4-nitrobenzoyl-L-glutamate (II) was reduced to di-tert-butyl 4-aminobenzoyl-L-glutamate (III) using transfer hydrogenation. The reductive amination of (III) with chloroethanal yielded the monofunctional di-tert-butyl 4-[(2-chloroethyl)amino]benzoyl-L-glutamate (IV), which was N-alkylated with ethylene oxide to give di-tert-butyl 4-[(2-chloroethyl)(2-hydroxyethyl)amino]benzoyl-L-glutamate (V). Reaction of (V) with methanesulfonyl chloride at 5 C yielded di-tert-butyl 4-[(2-chloroethyl)[2-(mesyloxy)ethyl]amino]benzoyl-L-glutamate (VI). Treatment of (VI) with formic acid followed by lyophilization gave the diacid, 4-[(2-chloroethyl)[2-(mesyloxy)ethyl]amino]benzoyl-L-glutamic acid (VII).
| 【1】 Springer, C.J.; Mann, J.; Bagshawe, K.D.; Haase-Held, M.; Synthesis of an N-mustard prodrug. Tetrahedron 1990, 46, 5377-82. |
| 【2】 Antoniw, P.; Bisset, G.M.F.; Springer, C.J.; Searle, F.; Jarman, M.; Bagshawe, K.D.; Novel prodrugs which are activated to cytotoxic alkylating agents by carboxypeptidase G2. J Med Chem 1990, 33, 2, 677-81. |
| 【3】 Springer, C.J.; CMDA. Drugs Fut 1993, 18, 3, 212. |
| 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) | 18941 | p-nitrobenzoyl chloride; 4-nitrobenzoyl chloride | 122-04-3 | C7H4ClNO3 | 详情 | 详情 |
| (II) | 13674 | di(tert-butyl) (2S)-2-[(4-nitrobenzoyl)amino]pentanedioate | C20H28N2O7 | 详情 | 详情 | |
| (III) | 13675 | di(tert-butyl) (2S)-2-[(4-aminobenzoyl)amino]pentanedioate | C20H30N2O5 | 详情 | 详情 | |
| (IV) | 13676 | di(tert-butyl) (2S)-2-([4-[(2-chloroethyl)amino]benzoyl]amino)pentanedioate | C22H33ClN2O5 | 详情 | 详情 | |
| (V) | 13677 | di(tert-butyl) (2S)-2-([4-[(2-chloroethyl)(2-hydroxyethyl)amino]benzoyl]amino)pentanedioate | C24H37ClN2O6 | 详情 | 详情 | |
| (VI) | 13678 | di(tert-butyl) (2S)-2-[[4-((2-chloroethyl)[2-[(methylsulfonyl)oxy]ethyl]amino)benzoyl]amino]pentanedioate | C25H39ClN2O8S | 详情 | 详情 | |
| (VII) | 13679 | (2S)-2-[[4-((2-Chloroethyl)[2-[(methylsulfonyl)oxy]ethyl]amino)benzoyl]amino]pentanedioic acid | C17H23ClN2O8S | 详情 | 详情 | |
| (VIII) | 13680 | 4-((2-Chloroethyl)[2-[(methylsulfonyl)oxy]ethyl]amino)benzoic acid | C12H16ClNO5S | 详情 | 详情 |