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【结 构 式】 
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【药物名称】PDP, CC-1069 【化学名称】3-(3,4-Dimethoxyphenyl)-3-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)propionamide 【CA登记号】167887-03-8 【 分 子 式 】C19H18N2O5 【 分 子 量 】354.36571 |
【开发单位】Celgene (Originator) 【药理作用】Agents for Liver Cirrhosis, Antiarthritic Drugs, GASTROINTESTINAL DRUGS, IMMUNOMODULATING AGENTS, Immunomodulators, Liver and Biliary Tract Disorders, Treatment of, ONCOLYTIC DRUGS, TREATMENT OF MUSCULOSKELETAL & CONNECTIVE TISSUE DISEASES, Angiogenesis Inhibitors, IL-10 Production Enhancers, IL-12 Production Inhibitors, IL-1beta Production Inhibitors, Phosphodiesterase IV Inhibitors, TNF-alpha Production Inhibitors |
合成路线1
Condensation of veratraldehyde (I) with malonic acid and ammonium acetate in refluxing EtOH afforded 3-amino-3-(3,4-dimethoxyphenyl)propionic acid (II). The N-phthaloyl group was introduced in (II) by treatment with N-carbethoxyphthalimide (III) in the presence of Na2CO3. The resulting phthalimido acid (IV) was converted to the title amide via activation with carbonyl diimidazole, followed by treatment with ammonium hydroxide.
| 【1】 Fernandez-Martinez, E.; et al.; Effects of thalidomide and 3-phthalimido-3-(3,4-dimethoxyphenyl)-propanamide on bile duct obstruction-induced cirrhosis in the rat. Drug Dev Res 2001, 54, 4, 209. |
| 【2】 Muller, G.W.; Shire, M.G.; Wong, L.M.; Corral, L.G.; Patterson, R.T.; Chen, Y.; Stirling, D.I.; Thalidomide analogs and PDE4 inhibition. Bioorg Med Chem Lett 1998, 8, 19, 2669. |
| 【3】 Muller, G.W.; et al.; Structural modifications of thalidomide produce analogs with enhanced tumor necrosis factor inhibitory activity. J Med Chem 1996, 39, 17, 3238. |
| 【4】 Muller, G.W. (Celgene Corp.); Ring closure of N-phthaloylglutamines. EP 1004572; EP 1004580; US 5463063; WO 9501348 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| 12963 | Malonic acid | 141-82-2 | C3H4O4 | 详情 | 详情 | |
| (I) | 18304 | 3,4-Dimethoxybenzaldehyde; Veratraldehyde | 120-14-9 | C9H10O3 | 详情 | 详情 |
| (II) | 18306 | 3-(3,4-dimethoxyphenyl)-beta-alanine | C11H15NO4 | 详情 | 详情 | |
| (III) | 10283 | ethyl 1,3-dioxo-1,3-dihydro-2H-isoindole-2-carboxylate; N-Carbethoxyphthalimide | 22509-74-6 | C11H9NO4 | 详情 | 详情 |
| (IV) | 37235 | 3-(3,4-dimethoxyphenyl)-3-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)propionic acid | C19H17NO6 | 详情 | 详情 |