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【结 构 式】 
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【药物名称】Imiquimod, MTD-39, DZ-2636, R-837, S-26308, Zartra, Aldara 【化学名称】1-Isobutyl-1H-imidazo[4,5-c]quinolin-4-amine 【CA登记号】99011-02-6, 99011-78-6 (mono HCl salt) 【 分 子 式 】C14H16N4 【 分 子 量 】240.31042 |
【开发单位】3M Pharmaceuticals (Originator), Daiichi Pharmaceutical (Licensee), Mochida (Licensee) 【药理作用】Actinic Keratoses, Agents for, ANTIINFECTIVE THERAPY, Anti-Papilloma Virus Drugs, Antiviral Drugs, Basal Cell Carcinoma Therapy, DERMATOLOGIC DRUGS, Genital Warts, Treatment for, IMMUNOMODULATING AGENTS, Immunostimulants, Oncolytic Drugs, Interferon Inducers |
合成路线1
The condensation of 4-chloro-3-nitroquinoline (I) with isobutylamine in refluxing THF gives 4-(isobutylamino)-3-nitroquinoline (II), which by reduction with H2 over Pt/C in ethanol is converted to 3-amino-4-(isobutylamino)quinoline (III). The cyclization of (III) with triethyl orthoformate in refluxing formic acid affords 1-isobutyl-1H-imidazo[4,5-c]quinoline (IV), which is oxidized with 30% H2O2 in hot acetic acid yielding 1-isobutyl-1H-imidazo[4,5-c]quinolin-5-oxide (V). The reaction of (V) with refluxing POCl3 affords 4-chloro-1-isobutyl-1H-imidazo[4,5-c]quinoline (VI), which is finally treated with concentrated aqueous NH4OH at 150 C in a pressure vessel.
| 【1】 Gerster, J.F. (3M Pharmaceuticals); 1H-Imidazo[4,5-c]quinolines and 1H-imidazo[4, 5-c]quinolin-4-amines. EP 0145340; US 4689338; US 4698348 . |
| 【2】 Prous, J.; Castaner, J.; S-26308. Drugs Fut 1989, 14, 9, 870. |
| 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) | 11664 | 4-Chloro-3-nitroquinoline | C9H5ClN2O2 | 详情 | 详情 | |
| (II) | 21313 | N-isobutyl-3-nitro-4-quinolinamine | C13H15N3O2 | 详情 | 详情 | |
| (III) | 21314 | N-(3-amino-4-quinolinyl)-N-isobutylamine | C13H17N3 | 详情 | 详情 | |
| (IV) | 21315 | 1-isobutyl-1H-imidazo[4,5-c]quinoline | C14H15N3 | 详情 | 详情 | |
| (V) | 21316 | 1-isobutyl-1H-imidazo[4,5-c]quinolin-5-ium hydroxide | C14H17N3O | 详情 | 详情 | |
| (VI) | 21317 | 4-chloro-1-isobutyl-1H-imidazo[4,5-c]quinoline | C14H14ClN3 | 详情 | 详情 |