|
【结 构 式】 
|
【药物名称】NSC-D699127 【化学名称】5,5'-Bis[2-[4-[3-(dimethylaminopropoxy]phenyl]-1H-benzimidazole] 【CA登记号】234429-92-6 【 分 子 式 】C36H40N6O2 【 分 子 量 】588.7592 |
【开发单位】Institute of Cancer Research (Originator), Queen's University of Belfast (Originator), University of Reading (Originator) 【药理作用】ONCOLYTIC DRUGS, DNA-Damaging Drugs |
合成路线1
Acetylation of aniline (I) with acetic anhydride (Ac2O) in HOAc followed by reaction with mercurium acetate (Hg(OAc)2) and HClO4 in HOAc provides derivative (II), which is first subjected to dimerization by treatment with Cu and PdCl2 in pyridine and then nitrated by means of HNO3 in HOAc to afford substituted biphenyl (III). Hydrolysis of (III) with H2SO4 gives 4,4'-diamino-3,3'-dinitrobiphenyl (IV), which is converted into tetraaminobiphenyl (V) by hydrogenation over Raney-Ni in acetone. Mitsunobu reaction between p-hydroxybenzaldehyde (VI) and 3-dimethylamino propan-1-ol (VII) with PPh3 and DEAD in THF gives substituted benzaldehyde (VIII), which is finally cyclized with biphenyl derivative (V) by heating in nitrobenzene to furnish the target product.
| 【1】 Neidle, S.; et al.; Symmetric bis-benzimidazoles: New sequence-selective DNA-binding molecules. Chem Commun (London) 1999, 10, 929. |
| 【2】 Kelland, L.R.; Opoku-Boahen, Y.; Mann, J.; Baron, A.; johansson, E.; Parkinson, G.; Neidle, S.; A new class of symmetric bisbenzimidazole-based DNA minor groove-binding agents showing antitumor activity. J Med Chem 2001, 44, 2, 138. |
| 【3】 Mann, J.; Neidle, S. (Institute of Cancer Research; Queen's University of Belfast; University of Reading); Bis-benzazoles and their use as antineoplastic agents. WO 0063180 . |
| 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) | 12294 | Aniline; Phenylamine | 62-53-3 | C6H7N | 详情 | 详情 |
| (II) | 47202 | C10H11HgNO3 | 详情 | 详情 | ||
| (III) | 47203 | N-[4'-(acetamido)-3,3'-dinitro[1,1'-biphenyl]-4-yl]acetamide | C16H14N4O6 | 详情 | 详情 | |
| (IV) | 47204 | 3,3'-dinitro[1,1'-biphenyl]-4,4'-diamine; 4'-amino-3,3'-dinitro[1,1'-biphenyl]-4-ylamine | 6271-79-0 | C12H10N4O4 | 详情 | 详情 |
| (V) | 47205 | 3',4,4'-triamino[1,1'-biphenyl]-3-ylamine; [1,1'-biphenyl]-3,3',4,4'-tetramine | 91-95-2 | C12H14N4 | 详情 | 详情 |
| (VI) | 13433 | 4-Hydroxybenzaldehyde; p-Hydroxybenzaldehyde | 123-08-0 | C7H6O2 | 详情 | 详情 |
| (VII) | 37173 | 3-(dimethylamino)-1-propanol | 3179-63-3 | C5H13NO | 详情 | 详情 |
| (VIII) | 47206 | 4-[3-(dimethylamino)propoxy]benzaldehyde | C12H17NO2 | 详情 | 详情 |