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【结 构 式】 
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【药物名称】 【化学名称】8-(4'-Bromobiphenyl-4-yl)-8-oxooctanohydroxamic acid 【CA登记号】362670-51-7 【 分 子 式 】C20H22BrNO3 【 分 子 量 】404.30724 |
【开发单位】MethylGene (Originator) 【药理作用】ONCOLYTIC DRUGS, Histone Deacetylase Type I (HDAC1) Inhibitors |
合成路线1
The reaction of ethyl 7-bromoheptanoate (I) with NaI, Zn, dibromoethane, LiCl and CuCN gives the organometallic derivative (II), which is condensed with 4-bromobenzoyl chloride (III) in THF to yield 8-(4-bromophenyl)-8-oxooctanoic acid ethyl ester (IV). The condensation of (IV) with 4-bromophenylboronic acid (V) by means of Pd(PPh3)4 and K2CO3 in hot toluene affords 8-(4'-bromobiphenyl-4-yl)-8-oxooctanoic acid ethyl ester (VI), which is hydrolyzed with NaOH in THF/methanol to provide the corresponding carboxylic acid (VII). Finally, this compound is treated with hydroxylamine, EDC, HOBt and TEA to obtain the target hydroxamic acid.
| 【1】 Woo, S.H.; et al.; Structurally simple trichostatin A-like straight chain hydroxamates as potent histone deacetylase inhibitors. J Med Chem 2002, 45, 13, 2877. |
| 【2】 Delorme, D.; Woo, S.H.; Vaisburg, A. (MethylGene Inc.); Inhibitors of histone deacetylase. WO 0170675 . |
| 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) | 36428 | ethyl 7-bromoheptanoate | 29823-18-5 | C9H17BrO2 | 详情 | 详情 |
| (II) | 55802 | C10H17CuINO2Zn | 详情 | 详情 | ||
| (III) | 45960 | 4-bromobenzoyl chloride | 586-75-4 | C7H4BrClO | 详情 | 详情 |
| (IV) | 55803 | ethyl 8-(4-bromophenyl)-8-oxooctanoate | C16H21BrO3 | 详情 | 详情 | |
| (V) | 55804 | 4-Bromobenzeneboronic acid; 4-Bromophenylboronic acid | 5467-74-3 | C6H6BBrO2 | 详情 | 详情 |
| (VI) | 55805 | ethyl 8-(4'-bromo[1,1'-biphenyl]-4-yl)-8-oxooctanoate | C22H25BrO3 | 详情 | 详情 | |
| (VII) | 55806 | 8-(4'-bromo[1,1'-biphenyl]-4-yl)-8-oxooctanoic acid | C20H21BrO3 | 详情 | 详情 |