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【结 构 式】 
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【药物名称】Panobinostat, LBH-589, NVP-LBH-589 【化学名称】3-[4-[2-(2-Methyl-1H-indol-3-yl)ethylaminomethyl]phenyl]-2(E)-propenohydroxamic acid 【CA登记号】404950-80-7 【 分 子 式 】C21H23N3O2 【 分 子 量 】349.4263 |
【开发单位】Novartis (CH, US). 【药理作用】Histone deacetylase (HDAC) inhibitor, Apoptosis inducer, Oncolytic. |
合成路线1
Reduction of 2-methylindole-3-glyoxylamide (I) with LiAlH4 affords 2-methyltryptamine (II). 4-Formylcinnamic acid (III) is esterified with methanolic HCl, and the resulting aldehyde ester (IV) is reductively aminated with 2-methyltryptamine (II) in the presence of NaBH3CN to give (V). The title hydroxamic acid is then obtained by treatment of ester (V) with aqueous hydroxylamine under basic conditions (1). Scheme 1.
| 【1】 Bair, K.W., Green, M.A., Perez, L.B., Sharma, S.K., Sambucetti, L., Versace, R.W., Remiszewski, S.W. (Novartis AG; Novartis Pharma GmbH). Deacetylase inhibitors. EP 1318980, JP 2004509105, WO 0222577. |
| 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) | 65332 | 2-methylindole-3-glyoxylamide | C10H10N2O2 | 详情 | 详情 | |
| (II) | 65333 | 2-Methylindole-3-ethylamine; 2-(2-Methyl-1H-indol-3-yl)-ethylamine; 3-(2-Aminoethyl)-2-methylindole | 2731-06-8 | C11H14N2 | 详情 | 详情 |
| (III) | 55571 | 4-Formylcinnamic acid | 23359-08-2 | C10H8O3 | 详情 | 详情 |
| (IV) | 46515 | methyl (E)-3-(4-formylphenyl)-2-propenoate | 7560-50-1 | C11H10O3 | 详情 | 详情 |
| (V) | 65334 | C22H23N2O2 | 详情 | 详情 |