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【结 构 式】 
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【药物名称】Diethylnorspermine, DE-333, BE-333, CI-1006, DENSPM, BENSPM 【化学名称】1,11-Bis(ethylamino)-4,8-diazaundecane 【CA登记号】121749-39-1 【 分 子 式 】C13H32N4 【 分 子 量 】244.42679 |
【开发单位】Genzyme (Orphan Drug), University of Florida (Originator), Genzyme (Not Determined), Johns Hopkins University (Not Determined), Pfizer (Licensee), SunPharm (Licensee) 【药理作用】Breast Cancer Therapy, Liver Cancer Therapy, Melanoma Therapy, Oncolytic Drugs, Pancreatic Cancer Therapy, Renal Cancer Therapy, Solid Tumors Therapy, Antimetabolites, Ornithine Decarboxylase Inhibitors, S-Adenosyl-L-methionine Decarboxylase Inhibitors |
合成路线1
Alkylation of ethylamine (II) with 3-chloro-1-propanol (I) in a pressure vessel furnished 3-(ethylamino)-1-propanol (III). After protection of the secondary amine group of (III) upon treatment with benzyl chloroformate, the resultant N-(3-hydroxypropyl)carbamate (IV) was activated as the mesylate ester (V) with methanesulfonyl chloride and triethylamine.
| 【1】 Mignonac, S.; Guy, A.; De Lamer, V. (Sanofi-Synthelabo); Preparation of polyamine(s), substd. on terminal nitrogen atoms. FR 2714052 . |
| 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) | 19490 | 3-chloro-1-propanol | 627-30-5 | C3H7ClO | 详情 | 详情 |
| (II) | 10928 | Ethanamine | 75-04-7 | C2H7N | 详情 | 详情 |
| (III) | 59216 | 3-(ethylamino)-1-propanol | C5H13NO | 详情 | 详情 | |
| (IV) | 59217 | benzyl ethyl(3-hydroxypropyl)carbamate | C13H19NO3 | 详情 | 详情 | |
| (V) | 59218 | 3-[[(benzyloxy)carbonyl](ethyl)amino]propyl methanesulfonate | C14H21NO5S | 详情 | 详情 |
合成路线2
1,3-Diaminopropane (VI) was protected as the bis-sulfonamide (VIII) by acylation with mesitylenesulfonyl chloride (VII). The sodium salt of sulfonamide (VIII) was then alkylated with mesylate (V) in cold DMF/toluene to provide the fully protected tetraamine (IX). The sulfonyl and carbamate protecting groups of (IX) were finally removed by treatment with HCl in the presence of phenol at 80 C.
| 【1】 Mignonac, S.; Guy, A.; De Lamer, V. (Sanofi-Synthelabo); Preparation of polyamine(s), substd. on terminal nitrogen atoms. FR 2714052 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (V) | 59218 | 3-[[(benzyloxy)carbonyl](ethyl)amino]propyl methanesulfonate | C14H21NO5S | 详情 | 详情 | |
| (VI) | 19331 | 3-aminopropylamine; 1,3-propanediamine | 109-76-2 | C3H10N2 | 详情 | 详情 |
| (VII) | 41158 | 2,4,6-trimethylbenzenesulfonyl chloride | 773-64-8 | C9H11ClO2S | 详情 | 详情 |
| (VIII) | 59219 | N-{3-[(mesitylsulfonyl)amino]propyl}-2,4,6-trimethylbenzenesulfonamide | C21H30N2O4S2 | 详情 | 详情 | |
| (IX) | 59220 | benzyl ethyl[12-ethyl-4,8-bis(mesitylsulfonyl)-13-oxo-15-phenyl-14-oxa-4,8,12-triazapentadec-1-yl]carbamate | C47H64N4O8S2 | 详情 | 详情 |