【结 构 式】 |
【药物名称】WMC-79 【化学名称】5-Nitro-2-[3-[4-[3-(6-oxo-6H-imidazo[4,5,1-de]acridin-5-ylamino)propyl]piperazin-1-yl]propyl]benzo[de]isoquinoline-1,3(2H)-dione 【CA登记号】359630-61-8 【 分 子 式 】C36H33N7O5 【 分 子 量 】643.70831 |
【开发单位】National Cancer Institute (Originator) 【药理作用】Colorectal Cancer Therapy, Oncolytic Drugs, Pancreatic Cancer Therapy, Apoptosis Inducers, DNA-Intercalating Drugs |
合成路线1
2,6-Dichloro-3-nitrobenzoic acid (I) was condensed with aniline (II) to produce the anilinobenzoic acid (III), which was subsequently cyclized to the acridinone (IV) upon treatment with POCl3. Displacement of the chloride group of (IV) with 1,4-bis(3-aminopropyl)piperazine (V) in DMF afforded adduct (VI). The nitro group of (VI) was reduced by catalytic hydrogenation in the presence of Raney-Ni and formic acid, and the intermediate formamide was further cyclized under acidic conditions to the imidazoacridinone (VII). Finally, conversion of the primary amino group of (VII) to the target imide was achieved by heating with 3-nitro-1,8-naphthalenedicarboxylic anhydride (VIII) in DMF.
【1】 Cholody, W.M.; Michejda, C.J.; Kosakowska-Cholody, T. (US Department of Health & Human Services); 1,8-Naphthalimide imidazo[4,5,1-de]acridones with anti-tumor activity. WO 0166545 . |
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) | 52274 | 2,5-Dichloro-3-nitrobenzoic acid | 88-86-8 | C7H3Cl2NO4 | 详情 | 详情 |
(II) | 12294 | Aniline; Phenylamine | 62-53-3 | C6H7N | 详情 | 详情 |
(III) | 52275 | 6-chloro-3-nitro-2-(phenylamino)benzoic acid | C13H9ClN2O4 | 详情 | 详情 | |
(IV) | 52276 | 1-chloro-4-nitro-9(10H)-acridinone | C13H7ClN2O3 | 详情 | 详情 | |
(V) | 52277 | 1,4-Bis(3-aminopropyl)piperazine; N,N'-Bis(3-Aminopropyl)piperazine; Bis aminopropyl piperazine; 1,4-Di(3-aminopropyl)piperazine | 7209-38-3 | C10H24N4 | 详情 | 详情 |
(VI) | 52278 | 1-({3-[4-(3-aminopropyl)-1-piperazinyl]propyl}amino)-4-nitro-9(10H)-acridinone | C23H30N6O3 | 详情 | 详情 | |
(VII) | 52279 | 5-({3-[4-(3-aminopropyl)-1-piperazinyl]propyl}amino)-6H-imidazo[4,5,1-de]acridin-6-one | C24H30N6O | 详情 | 详情 | |
(VIII) | 15864 | 5-nitro-1H,3H-benzo[de]isochromene-1,3-dione; 3-Nitro-1,8-naphthalic anhydride | 3027-38-1 | C12H5NO5 | 详情 | 详情 |