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【结 构 式】 
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【药物名称】Epinastine hydrochloride, WAL-801CL, Elestat, Relestat, Flurinol, Alesion 【化学名称】3-Amino-9,13b-dihydro-1H-dibenz[c,f]imidazol[1,5-a]azepine hydrochloride 【CA登记号】80012-43-7 (free base) 【 分 子 式 】C16H16ClN3 【 分 子 量 】285.77902 |
【开发单位】Boehringer Ingelheim (Originator), Nippon Boehringer Ingelheim (Originator), Allergan (Licensee), Inspire Pharmaceuticals (Comarketer), Sankyo (Comarketer) 【药理作用】Allergic Skin Disorders, Treatment for, Antiallergic Ophthalmic Agents, Antiallergy/Antiasthmatic Drugs, Asthma Therapy, DERMATOLOGIC DRUGS, Drugs for Allergic Rhinitis, Ocular Antiinflammatory and Antiinfective Agents, OCULAR MEDICATIONS, Ophthalmic Drugs, RESPIRATORY DRUGS, Treatment of Upper Respiratory Tract Disorders, Histamine H1 Antagonists |
合成路线1
| 【1】 Masagaki T, Kakita T, et aL 2001. Preparation of antiallergic epinatine and imidazoline compounds as their intermediates. JP 2001064282 |
| 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) | 32278 | ethyl 2-aminobenzoate | 87-25-2 | C9H11NO2 | 详情 | 详情 |
| (II) | 66334 | ethyl 2-((2-amino-1-phenylethyl)amino)benzoate | C17H20N2O2 | 详情 | 详情 | |
| (III) | 66335 | (2-((2-amino-1-phenylethyl)amino)phenyl)methanol | C15H18N2O | 详情 | 详情 | |
| (IV) | 66336 | N-((2-((2-(hydroxymethyl)phenyl)amino)-2-phenylethyl)carbamoyl)benzamide | C23H23N3O3 | 详情 | 详情 | |
| (V) | 66337 | N-(1-(2-(hydroxymethyl)phenyl)-5-phenyl-4,5-dihydro-1H-imidazol-2-yl)benzamide | C23H21N3O2 | 详情 | 详情 | |
| (VI) | 23530 | benzoyl isothiocyanate | 532-55-8 | C8H5NOS | 详情 | 详情 |
合成路线2
| 【1】 Kawahan H, Mori M, etal.2002. Preparation of 6-aminomethyl-6,11-dihydro-5H-dibenzo[b.e]azepine as intermediate for epinastine, hydrochloride,antiallergyagent. JP 2002308851 |
| 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) | 62393 | 2-benzylaniline; 2-benzylphenylamine | 28059-64-5 | C13H13N | 详情 | 详情 |
| (II) | 66338 | 2-benzyl-N-(3-chloroprop-1-en-2-yl)aniline | C16H16ClN | 详情 | 详情 | |
| (III) | 62395 | 6-(chloromethyl)-11H-dibenzo[b,e]azepine | 21535-44-4 | C15H12ClN | 详情 | 详情 |
| (IV) | 66339 | 2-((11H-dibenzo[b,e]azepin-6-yl)methyl)isoindoline-1,3-dione | C23H16N2O2 | 详情 | 详情 | |
| (V) | 66340 | 6-(Phthalimidomethyl)-6,11-dihydro-5H-dibenz[b,e]azepine | 143878-20-0 | C23H18N2O2 | 详情 | 详情 |
| (VI) | 12465 | 6,11-Dihydro-5H-dibenzo[b,e]azepin-6-ylmethylamine; 6,11-Dihydro-5H-dibenzo[b,e]azepin-6-ylmethanamine | C15H16N2 | 详情 | 详情 | |
| (VII) | 10926 | (1,3-Dioxo-1,3-dihydro-2H-isoindol-2-yl)potassium | C8H4KNO2 | 详情 | 详情 |
合成路线3
A new synthesis of epinastine hydrochloride has been described: The reaction of 6-chloro-11H-dibenzo[b,e]azepine (I) with NaCN in DMSO at 90 C gives 11H-dibenzo[b,e]azepine-6-carbonitrile (II), which is reduced with AlH3 (prepared from LiAlH4 and H2SO4 in THF) in THF to afford 6-(aminomethyl)-6,11-dihydro-5H-dibenzo[b,e]azepine (III). Finally, this compound is cyclized with cyanogen bromide in THF and treated with HCl.
| 【1】 Walther, G.; Bechtel, W.D.; Daniel, H.; Brandt, K.; New tetracyclic guanidine derivatives with H1-antihistaminic properties. Chemistry of epinastine. Arzneim-Forsch Drug Res 1990, 40, 4, 440-6. |