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【结 构 式】 
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【药物名称】EDP-137 【化学名称】5-[(3aS,4S,6aR)-3a,4,6a-Trimethyl-2-oxoperhydrothieno[3,4-d]imidazol-4-yl]pentanoic acid 7-[N-[2-(2-azidophenyl)ethyl]-N-methylamino]-4-cyano-4-(3,4-dimethoxyphenyl)heptyl ester 【CA登记号】 【 分 子 式 】C38H53N7O5S 【 分 子 量 】719.95401 |
【开发单位】Università degli Studi di Firenze (Originator), Université paris Nord (Originator) 【药理作用】Modulators of the Therapeutic Activity of Antineoplastic Agents, Multidrug Resistance Modulators, ONCOLYTIC DRUGS |
合成路线1
Acetonitrile derivative (I) is treated with BuLi and alkylated with 3-bromopropanol (A) to yield alcohol (II), which is further alkylated by means of LICKOR (n-BuLi/t-BuOK) and 1-chloro-3-bromopropane (B) to afford (III). Reaction of derivative (III) with secondary amine (VIII) in acetonitrile gives (IV). Amine (VIII) is obtained by trifluoroacetylation of azide (VI) with trifluoroacetic anhydride to yield (VII), which is then N-methylated by means of MeI and hydrolyzed with KOH. Finally, alcohol (IV) reacts with succinimido biotinate (V) in DMSO to provide the desired product.
| 【1】 Teodori, E.; et al.; Synthesis and binding properties of photoactivable biotin-conjugated verapamil derivatives for the study of P-170 glycoprotein. Bioorg Med Chem 1999, 7, 9, 1873. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (A) | 12573 | 3-Bromo-1-propanol; 3-Bromopropanol | 627-18-9 | C3H7BrO | 详情 | 详情 |
| (B) | 19490 | 3-chloro-1-propanol | 627-30-5 | C3H7ClO | 详情 | 详情 |
| (I) | 25857 | 2-(3,4-dimethoxyphenyl)acetonitrile | 93-17-4 | C10H11NO2 | 详情 | 详情 |
| (II) | 42244 | 2-(3,4-dimethoxyphenyl)-5-hydroxypentanenitrile | C13H17NO3 | 详情 | 详情 | |
| (III) | 42245 | 5-chloro-2-(3,4-dimethoxyphenyl)-2-(3-hydroxypropyl)pentanenitrile | C16H22ClNO3 | 详情 | 详情 | |
| (IV) | 42249 | 5-[(2-azidophenethyl)(methyl)amino]-2-(3,4-dimethoxyphenyl)-2-(3-hydroxypropyl)pentanenitrile | C25H33N5O3 | 详情 | 详情 | |
| (V) | 42250 | 1-([5-[(3aS,4S,6aR)-3a,4,6a-trimethyl-2-oxohexahydro-1H-thieno[3,4-d]imidazol-4-yl]pentanoyl]oxy)-2,5-pyrrolidinedione | C17H25N3O5S | 详情 | 详情 | |
| (VI) | 42246 | 2-azidophenethylamine; 2-(2-azidophenyl)-1-ethanamine | C8H10N4 | 详情 | 详情 | |
| (VII) | 42247 | N-(2-azidophenethyl)-2,2,2-trifluoroacetamide | C10H9F3N4O | 详情 | 详情 | |
| (VIII) | 42248 | N-(2-azidophenethyl)-N-methylamine; 2-(2-azidophenyl)-N-methyl-1-ethanamine | C9H12N4 | 详情 | 详情 |