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【结 构 式】 
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【药物名称】Teriflunomide, HMR-1726, 1726, A-771726, RS-61980, SU-0020 【化学名称】(Z)-2-Cyano-3-hydroxy-N-[4-(trifluoromethyl)phenyl]-2-butenamide 【CA登记号】108605-62-5, 282716-73-8 (monosodium salt) 【 分 子 式 】C12H9F3N2O2 【 分 子 量 】270.21293 |
【开发单位】Aventis Pharma (Originator), Sugen (Licensee) 【药理作用】Antiarthritic Drugs, Disease-Modifying Drugs, Immunologic Neuromuscular Disorders, Treatment of, IMMUNOMODULATING AGENTS, Immunosuppressants, Multiple Sclerosis, Agents for, NEUROLOGIC DRUGS, TREATMENT OF MUSCULOSKELETAL & CONNECTIVE TISSUE DISEASES, Dihydroorotate Dehydrogenase Inhibitors |
合成路线1
5-Methylisoxazole-4-carboxylic acid (I) was converted to the corresponding acid chloride (II) upon refluxing with SOCl2. Coupling of acid chloride (II) with 4-(trifluoromethyl)aniline (III) produced anilide (IV). Finally, isoxazole ring opening in the presence of NaOH gave rise to the title cyano amide.
| 【1】 Bartlett, R.R.; Kämmerer, F.-J. (Aventis SA); Isoxazole-4-carboxamides and hydroxyalkylidene-cyanoacetamides, drugs containing these cpds. and use of such drugs. EP 0527736; JP 1993506425; JP 1999322700; JP 1999343285; US 5494911; US 5532259; WO 9117748 . |
| 【2】 Coghlan, M.J.; Luly, J.R.; Wiedeman, P.E. (Abbott Laboratories Inc.); Immunosuppressive agents. WO 9424095 . |
| 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) | 17340 | 5-methyl-4-isoxazolecarboxylic acid | 42831-50-5 | C5H5NO3 | 详情 | 详情 |
| (II) | 17341 | 5-methyl-4-isoxazolecarbonyl chloride | 67305-24-2 | C5H4ClNO2 | 详情 | 详情 |
| (III) | 17333 | 4-(trifluoromethyl)aniline; p-Trifluoromethylaniline; 4-(trifluoromethyl)phenylamine; 4-aminobenzotrifluoride | 455-14-1 | C7H6F3N | 详情 | 详情 |
| (IV) | 54580 | 5-methyl-N-[4-(trifluoromethyl)phenyl]-4-isoxazolecarboxamide | C12H9F3N2O2 | 详情 | 详情 |