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【结 构 式】 
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【药物名称】SB-425076 【化学名称】2-[3-(6-Ethyl-8-iodo-1,2,3,4-tetrahydroquinolin-4-ylamino)propylamino]quinolin-4(1H)-one dihydrochloride 【CA登记号】263896-15-7 【 分 子 式 】C23H29Cl2IN4O 【 分 子 量 】575.32418 |
【开发单位】GlaxoSmithKline (Originator) 【药理作用】Antibacterial Drugs, ANTIINFECTIVE THERAPY, Methionyl-tRNA Synthetase Inhibitors |
合成路线1
Condensation of 4-ethylaniline (I) with propiolactone (II) produces the beta-aminoacid (III). Intramolecular Friedel-Crafts cyclization of (III) by means of polyphosphoric acid leads to the quinolinone (IV). Then, electrophilic iodination of (IV) by using iodine monochloride provides the intermediate (V)
| 【1】 Jarvest, R.L.; Berge, J.M.; Berry, V.; et al.; Nanomolar inhibitors of Staphylococcus aureus methionyl tRNA synthetase with potent antibacterial activity against Gram-positive pathogens. J Med Chem 2002, 45, 10, 1959. |
| 【2】 Berge, J.M.; Forrest, A.K.; Elder, J.S.; Jarvest, R.L. (GlaxoSmithKline plc); Quinolones as t-RNA synthetase inhibitors and antibacterial agents. WO 0021949 . |
| 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) | 60623 | 4-ethylaniline; 4-ethylphenylamine | C8H11N | 详情 | 详情 | |
| (II) | 24477 | 2-oxetanone | 57-57-8 | C3H4O2 | 详情 | 详情 |
| (III) | 60624 | 3-(4-ethylanilino)propanoic acid | C11H15NO2 | 详情 | 详情 | |
| (IV) | 60625 | 6-ethyl-2,3-dihydro-4(1H)-quinolinone | C11H13NO | 详情 | 详情 | |
| (V) | 60626 | 6-ethyl-8-iodo-2,3-dihydro-4(1H)-quinolinone | C11H12INO | 详情 | 详情 |
合成路线2
Displacement of 2-chloro-4-ethoxyquinoline (VI) with 1,3-propanediamine (VII) affords the aminoquinoline (VIII). Subsequent acidic hydrolysis of (VIII) provides quinolinone (IX). Finally, reductive condensation between amine (IX) and ketone (V) in the presence of NaBH3CN leads to the target disubstituted propanediamine
| 【1】 Jarvest, R.L.; Berge, J.M.; Berry, V.; et al.; Nanomolar inhibitors of Staphylococcus aureus methionyl tRNA synthetase with potent antibacterial activity against Gram-positive pathogens. J Med Chem 2002, 45, 10, 1959. |
| 【2】 Berge, J.M.; Forrest, A.K.; Elder, J.S.; Jarvest, R.L. (GlaxoSmithKline plc); Quinolones as t-RNA synthetase inhibitors and antibacterial agents. WO 0021949 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (V) | 60626 | 6-ethyl-8-iodo-2,3-dihydro-4(1H)-quinolinone | C11H12INO | 详情 | 详情 | |
| (VI) | 60627 | 2-chloro-4-ethoxyquinoline; 2-chloro-4-quinolinyl ethyl ether | C11H10ClNO | 详情 | 详情 | |
| (VII) | 19331 | 3-aminopropylamine; 1,3-propanediamine | 109-76-2 | C3H10N2 | 详情 | 详情 |
| (VIII) | 60628 | N-(3-aminopropyl)-N-(4-ethoxy-2-quinolinyl)amine; N~1~-(4-ethoxy-2-quinolinyl)-1,3-propanediamine | C14H19N3O | 详情 | 详情 | |
| (IX) | 60629 | 2-[(3-aminopropyl)amino]-4(1H)-quinolinone | C12H15N3O | 详情 | 详情 |