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【结 构 式】

【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
      2-(2-Phathalimidoethoxy)acetyl-L-alanyl-D-isoglutamine

【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
Extended Information