|
【结 构 式】 
|
【药物名称】TSU-68, SU-6668 【化学名称】(Z)-3-[2,4-Dimethyl-5-(2-oxo-2,3-dihydro-1H-indol-3-ylidenemethyl)-1H-pyrrol-3-yl]propionic acid 【CA登记号】252916-29-3 【 分 子 式 】C18H18N2O3 【 分 子 量 】310.35576 |
【开发单位】Sugen (Originator), Taiho (Licensee), Cancer Research UK (Codevelopment) 【药理作用】Oncolytic Drugs, Solid Tumors Therapy, Angiogenesis Inhibitors, FGFR Inhibitors, Inhibitors of Signal Transduction Pathways, PDGFR Inhibitors, VEGFR-2 (FLK-1/KDR) Inhibitors |
合成路线1
Basic hydrolysis of the known 2,4-dimethyl-5-ethoxycarbonyl-3-(2-ethoxycarbonyl ethyl)pyrrole (I) and subsequent decarboxylation of the resulting diacid (II) in the presence of HCl furnished 2,4-dimethyl-3-pyrrolepropionic acid (III). Vilsmeier formylation of (III) employing dimethylformamide and POCl3 produced aldehyde (IV). The title compound was then obtained by condensation of aldehyde (IV) with oxindole (V) in the presence of pyrrolidine, followed by acid treatment of the intermediate (VI). Alternatively, direct condensation of aldehyde (IV) with oxindole (V) in the presence of NaOH gave rise to the title compound.
| 【1】 Tang, P.C.; Sun, L.; McMahon, G. (Sugen, Inc.); Pyrrole substd. 2-indolinone protein kinase inhibitors. WO 9961422 . |
| 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) | 39751 | ethyl 4-(3-ethoxy-3-oxopropyl)-3,5-dimethyl-1H-pyrrole-2-carboxylate | C14H21NO4 | 详情 | 详情 | |
| (II) | 39752 | 4-(2-carboxyethyl)-3,5-dimethyl-1H-pyrrole-2-carboxylic acid | C10H13NO4 | 详情 | 详情 | |
| (III) | 39753 | 3-(2,4-dimethyl-1H-pyrrol-3-yl)propionic acid | C9H13NO2 | 详情 | 详情 | |
| (IV) | 39754 | 3-(5-formyl-2,4-dimethyl-1H-pyrrol-3-yl)propionic acid | C10H13NO3 | 详情 | 详情 | |
| (V) | 18699 | 1,3-dihydro-2H-indol-2-one | 59-48-3 | C8H7NO | 详情 | 详情 |
| (VI) | 39755 | 3-[2,4-dimethyl-5-[(2-oxo-2,3-dihydro-1H-indol-3-yl)(1-pyrrolidinyl)methyl]-1H-pyrrol-3-yl]propionic acid | C22H27N3O3 | 详情 | 详情 |