|
【结 构 式】 
|
【药物名称】 【化学名称】9(S),16-Diethyl-9-hydroxy-1,2,3,9,12,15-hexahydro-10H,13H-pyrano[3'',4'':6',7']indolizino[2',1':5,6]pyrido[3,2-f][1,4]benzoxazine-10,13-dione 【CA登记号】344957-91-1 【 分 子 式 】C24H23N3O5 【 分 子 量 】433.46801 |
【开发单位】SK Chemicals (Originator) 【药理作用】Oncolytic Drugs, Camptothecins, DNA Topoisomerase I Inhibitors, DNA-Intercalating Drugs |
合成路线1
Alkylation of 7-ethyl-10-hydroxycamptothecin (I) with 1,2-dibromoethane (II) under Williamson's ether synthesis conditions furnished the bromoethyl ether (III). Subsequent regioselective nitration of (III) provided the desired 9-nitro compound (IV), which was further reduced to the corresponding amine (V) by using SnCl2 in concentrated HCl. Finally, cyclization of the bromo amine (V) to give the title hexacyclic compound was carried out either in the presence of KI and K2CO3 in refluxing acetone or on standing in a DMSO solution at room temperature.
| 【1】 Kim, D.-K.; et al.; Synthesis and biological evaluation of novel A-ring modified hexacyclic camptothecin analogues. J Med Chem 2001, 44, 10, 1594. |
| 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) | 10819 | (4S)-4,11-Diethyl-4,9-dihydroxy-1H-pyrano[3',4':6,7]indolizino[1,2-b]quinoline-3,14(4H,12H)-dione; 7-Ethyl-10-hydroxycamptothecin | C22H20N2O5 | 详情 | 详情 | |
| (II) | 10252 | 1,2-Dibromoethane; Ethylene dibromide | 106-93-4 | C2H4Br2 | 详情 | 详情 |
| (III) | 50975 | (4S)-9-(2-bromoethoxy)-4,11-diethyl-4-hydroxy-1H-pyrano[3',4':6,7]indolizino[1,2-b]quinoline-3,14(4H,12H)-dione | C24H23BrN2O5 | 详情 | 详情 | |
| (IV) | 50976 | (4S)-9-(2-bromoethoxy)-4,11-diethyl-4-hydroxy-10-nitro-1H-pyrano[3',4':6,7]indolizino[1,2-b]quinoline-3,14(4H,12H)-dione | C24H22BrN3O7 | 详情 | 详情 | |
| (V) | 50977 | (4S)-10-amino-9-(2-bromoethoxy)-4,11-diethyl-4-hydroxy-1H-pyrano[3',4':6,7]indolizino[1,2-b]quinoline-3,14(4H,12H)-dione | C24H24BrN3O5 | 详情 | 详情 |