|
【结 构 式】 
|
【药物名称】Topotecan hydrochloride, E-89/001, NSC-609699, SK&F-S-104864-A, Evotropin, Hycamtin 【化学名称】(S)-10-Dimethylaminomethyl-9-hydroxycamptothecin monohydrochloride 【CA登记号】119413-54-6, 123948-88-9 (acetate salt), 123948-87-8 (free base) 【 分 子 式 】C23H24ClN3O5 【 分 子 量 】457.91783 |
【开发单位】GlaxoSmithKline (Originator), National Cancer Institute (Codevelopment) 【药理作用】Colorectal Cancer Therapy, Leukemia Therapy, Lung Cancer Therapy, Myelodysplastic Syndrome Therapy, Non-Small Cell Lung Cancer Therapy, Oncolytic Drugs, Ovarian Cancer Therapy, Small Cell Lung Cancer Therapy, Solid Tumors Therapy, DNA Topoisomerase I Inhibitors |
合成路线1
The reduction of camptothecin (I) with H2 over PtO2 in acetic acid, followed by oxidative acylation with lead tetraacetate and acetic acid and hydrolysis with acetic acid/water gives 9-hydroxycamptothecin (II), which is then treated with formaldehyde and dimethylamine in acetic acid. The hydrochloride salt is prepared by treatment of the acetic acid solution with diluted HCl.
| 【1】 Castaner, J.; Spiridonidis, C.H.; Topotecan Hydrochloride. Drugs Fut 1995, 20, 5, 483. |
| 【2】 Boehm, J.C.; Johnson, R.K.; Hecht, S.M.; Kingsbury, W.D.; Holden, K.G. (SmithKline Beecham plc); Water soluble camptothecin analogs. AU 8826394; EP 0321122; JP 1989186893; US 5004758 . |
| 【3】 Boehm, J.C.; Kingsbury, W.D.; Jakas, D.R.; et al.; Synthesis of water soluble (aminoalkyl) camptothecin analogues: Inhibition of topoisomerase I and antitumor activity. J Med Chem 1991, 34, 1, 98-107. |
| 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) | 10816 | Camptothecin; (4S)-4-Ethyl-4-hydroxy-1H-pyrano[3',4':6,7]indolizino[1,2-b]quinoline-3,14(4H,12H)-dione; 4-et-4-hydroxy-1,12-dihydro-4h-2-oxa-6,12a-diaza-dibenzo(b,h)fluorene-3,13-dione | 7689-03-4 | C20H16N2O4 | 详情 | 详情 |
| (II) | 13340 | (4S)-4-Ethyl-4,9-dihydroxy-1H-pyrano[3',4':6,7]indolizino[1,2-b]quinoline-3,14(4H,12H)-dione; 7-Ethyl-10-hydroxycamptothecin | 86639-52-3 | C20H16N2O5 | 详情 | 详情 |