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【结 构 式】 
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【药物名称】DB-075, DB-75 【化学名称】4,4'-(2,5-Furandiyl)bis(benzamidine) 【CA登记号】73819-26-8, 55368-40-6 (as dihydrochloride) 【 分 子 式 】C18H16N4O 【 分 子 量 】304.35442 |
【开发单位】Georgia State University (Originator), University of North Carolina (Originator), Immtech (Licensee), CombinatoRx (Codevelopment) 【药理作用】AIDS Medicines, ANTIINFECTIVE THERAPY, ONCOLYTIC DRUGS, Treatment of Opportunistic Infections, Treatment of Protozoal Diseases |
合成路线1
The Friedel Crafts condensation of fumaryl chloride (I) with bromobenzene (II) gives 1,2-bis(4-bromobenzoyl)ethylene (III), which is reduced with Zn and Ac-OH to yield 1,4-bis(4-bromophenyl)butane-1,4-dione (IV). The cyclization of (IV) in refluxing Ac2O affords 2,5-bis(4-bromophenyl)furan (V) which is treated with CNCu in refluxing quinoline to provide 2,5-bis(4-cyanophenyl)furan (VI). The reaction of (VI) with HCl in ethanol gives the bis imidate (VII), which is finally treated with ammonia in ethanol to yield the target bis benzamidine.
| 【1】 Dann, O.; et al.; Trypanocidal diamidines with three isolated ring systems. Liebigs Ann Chem 1975, 1, 160. |
| 【2】 Das, B.P.; Boykin, D.W.; Synthesis and antiprotozoal activity of 2,5-bis (4-guanylphenyl) furans. J Med Chem 1977, 20, 4, 531-536. |
| 【3】 Boykin, D.W.; et al.; 2,5-Bis[4-(N-alkylamidino)phenyl]furans as anti-Pneumocystis carinii agents. J Med Chem 1998, 41, 1, 124. |
| 【4】 Boykin, D.W.; et al.; Anti-pneumocystis activity of bis-amidoximes and bis-O-alkylamidoximes prodrugs. Bioorg Med Chem Lett 1996, 6, 24, 3017. |
| 【5】 Niigata, K.; Murakami, M.; Kagami, S.; Fujikura, S.; Kojima, A.; Tachikawa, S.; Nozaki, J.; Takahashi, K. (Yamanouchi Pharmaceutical Co., Ltd.); Novel indene derivs. or their salts. JP 1977111580 . |
| 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) | 57909 | Fumaryl chloride | 627-63-4 | C4H2Cl2O2 | 详情 | 详情 |
| (II) | 13365 | Monobromobenzene; 1-Bromobenzene；Phenylbromide;bromobenzene | 108-86-1 | C6H5Br | 详情 | 详情 |
| (III) | 57910 | (E)-1,4-bis(4-bromophenyl)-2-butene-1,4-dione | C16H10Br2O2 | 详情 | 详情 | |
| (IV) | 35811 | 1,4-bis(4-bromophenyl)-1,4-butanedione | C16H12Br2O2 | 详情 | 详情 | |
| (V) | 35812 | 2,5-bis(4-bromophenyl)furan | C16H10Br2O | 详情 | 详情 | |
| (VI) | 56856 | Copper (I) cyanide; Cuprous cyanide | 544-92-3 | CCuN | 详情 | 详情 |
| (VII) | 35814 | 4-[5-(4-cyanophenyl)-2-furyl]benzonitrile | C18H10N2O | 详情 | 详情 | |
| (VIII) | 35815 | ethyl 4-(5-[4-[ethoxy(imino)methyl]phenyl]-2-furyl)benzenecarboximidoate | C22H22N2O3 | 详情 | 详情 |