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【结 构 式】 
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【药物名称】Mycophenolate mofetil, RS-61443-190(HCl), ME-MPA, RS-61443, Munoloc, CellCept 【化学名称】6-(4-Hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydroisobenzofuran-5-yl)-4-methyl-4(E)-hexenoic acid 2-(4-morpholinyl)ethyl ester 【CA登记号】128794-94-5, 115007-34-6 (deleted CAS), 140401-05-4 (deleted CAS), 116680-01-4 (HCl) 【 分 子 式 】C23H31NO7 【 分 子 量 】433.50602 |
【开发单位】Chugai (Originator), Roche (Originator), Roche Bioscience (Originator), Aspreva (Licensee), Johann Wolfgang Goethe Universität (Codevelopment) 【药理作用】Antipsoriatics, Atopic Dermatitis, Agents for, DERMATOLOGIC DRUGS, Immunologic Neuromuscular Disorders, Treatment of, IMMUNOMODULATING AGENTS, Multiple Sclerosis, Agents for, NEUROLOGIC DRUGS, Systemic Lupus Erythematosus, Agents for, Treatment of Autoimmune Diseases, TREATMENT OF MUSCULOSKELETAL & CONNECTIVE TISSUE DISEASES, Treatment of Other Autoimmune Disorders, Treatment of Transplant Rejection, Inosine 5'-Monophosphate Dehydrogenase (IMPDH) Inhibitors |
合成路线1
Commercially available mycophelonic acid (I) is converted to its chloride (II) by means of thionyl chloride in dichloromethane/DMF and then esterified with 2-(4-morpholinyl)ethanol (III) in dichloromethane.
| 【1】 Robinson, C.; Castaner, J.; Mycophenolate Mofetil. Drugs Fut 1995, 20, 4, 356. |
| 【2】 Allison, A.C.; Eugui, E.M.; Nelson, P.H.; Gu, C.-L.L.; Lee, W.A. (Syntex (USA), Inc.); Treatment of allograft rejection with mycophenolic acid morpholinoethyl ester and derivs. Thereof. US 4786637 . |
| 【3】 Nelson, P.H.; Gu, C.-L.L.; Allison, A.C.; Eugui, E.M.; Lee, W.A. (Syntex (USA), Inc.); Morpholinoethylesters of mycophenolic acid and pharmaceutical compsns. AU 8782540; EP 0281713; JP 1988188672; US 4753935 . |
| 【4】 Leung, K.; Nelson, P.H.; Miksztal, A.R.; Lee, W.A.; Gu, L.; Chu, N.; Bioavailability improvement of mycophenolic acid through amino ester derivatization. Pharm Res 1990, 7, 2, 161-6. |
| 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) | 12854 | Mycophenolic acid; (E)-6-(4-Hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)-4-methyl-4-hexenoic acid | 483-60-3 | C17H20O6 | 详情 | 详情 |
| (II) | 12855 | (E)-6-(4-Hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)-4-methyl-4-hexenoyl chloride | C17H19ClO5 | 详情 | 详情 | |
| (III) | 12856 | 4-(2-Hydroxyethyl)morpholine; 2-(4-Morpholinyl)-1-ethanol; N-(2-Hydroxyethyl)morpholine | 622-40-2 | C6H13NO2 | 详情 | 详情 |
合成路线2
The esterification of mycophenolic acid (I) with 2-(4-morpholinyl)ethanol (II) in refluxing dibutyl ether or refluxing dipentyl ether with azeotropic distillation of water gives the target mycophenolic ester.
| 【1】 Chudlik, M.; Husek, A. (Galena AS; Ivax Corp.); Method of mycophenolate mofetil preparation. WO 02100855 . |