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【结 构 式】 
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【药物名称】LK-423 【化学名称】2-[2-(1,3-Dioxo-1,3-dihydro-2H-isoindol-2-yl)ethoxy]acetyl-L-alanyl-D-glutamic acid 1-amide 【CA登记号】142489-46-1 【 分 子 式 】C20H24N4O8 【 分 子 量 】448.43628 |
【开发单位】LEK (Originator), University of Ljubljana (Originator), Fujimoto (Licensee) 【药理作用】Antiarthritic Drugs, GASTROINTESTINAL DRUGS, IMMUNOMODULATING AGENTS, Immunomodulators, Inflammatory Bowel Disease, Agents for, TREATMENT OF MUSCULOSKELETAL & CONNECTIVE TISSUE DISEASES |
合成路线1
The reaction of phthalimidocarboxylic acid ethyl ester (I) with 2-(2-aminoethoxy)ethanol (II) in THF gives N-[2-(2-hydroxyethoxy)ethyl]phthalimide (III), which is oxidized with CrO3/sulfuric acid in acetone yielding 2-(phthalimidoethoxy)acetic acid (IV). The condensation of (IV) with L-alanyl-D-isoglutamine benzyl ester (V) by means of phenylphosphoryl azide (DPPA) and triethylamine in DMF gives N-[2-(2-phthalimidoethoxy)acetyl]-L-alanyl-D-isoglutamine benzyl ester (VI), which is finally debenzylated by hydrogenation over Pd/C in acetic acid.
| 【1】 Urleb, U.; et al.; Synthesis of phthalimido-desmuramylpeptide analogues as potential immunomodulating agents. Arch Pharm 1995, 328, 2, 113. |
| 【2】 Pecar, S.; Sollner, M.; Urleb, U.; Kikelj, D.; Marc, G.; Krbavcic, A.; Kotnik, V.; Wraber-Herzog, B.; Simcic, S.; Ihan, A.; Klamfer, L.; Provsic, L.; Kopitar, Z.; Stalc, A. (LEK Pharmaceutical and Chemical Co.; University of Ljubljana); Novel N-acyldipeptides, processes for the preparation thereof and pharmaceutical compsns. containing the same. EP 0477912; JP 1994220087 . |
| 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) | 10283 | ethyl 1,3-dioxo-1,3-dihydro-2H-isoindole-2-carboxylate; N-Carbethoxyphthalimide | 22509-74-6 | C11H9NO4 | 详情 | 详情 |
| (II) | 19029 | 2-(2-aminoethoxy)-1-ethanol | 929-06-6 | C4H11NO2 | 详情 | 详情 |
| (III) | 27128 | 2-[2-(2-hydroxyethoxy)ethyl]-1H-isoindole-1,3(2H)-dione | C12H13NO4 | 详情 | 详情 | |
| (IV) | 27129 | 2-[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethoxy]acetic acid | C12H11NO5 | 详情 | 详情 | |
| (V) | 27130 | benzyl (4R)-5-amino-4-[[(2S)-2-aminopropanoyl]amino]-5-oxopentanoate | C15H21N3O4 | 详情 | 详情 | |
| (VI) | 27131 | benzyl (4R)-5-amino-4-[[(2S)-2-([2-[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethoxy]acetyl]oxy)propanoyl]amino]-5-oxopentanoate | C27H29N3O9 | 详情 | 详情 |