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【结 构 式】 
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【药物名称】 【化学名称】N'-[1-[4(S)-(3-Amino-2,3,6-trideoxy-alpha-L-lyxo-hexopyranosyloxy)-2(S),5,12-trihydroxy-7-methoxy-6,11-dioxo-1,2,3,4,6,11-hexahydronaphthacen-2-yl]-2-hydroxyethylidene]-6-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)hexanohydrazide hydrochloride 【CA登记号】151038-96-9 (free base) 【 分 子 式 】C37H43ClN4O13 【 分 子 量 】787.22726 |
【开发单位】Bristol-Myers Squibb (Originator) 【药理作用】Chemical Delivery Systems, DRUG DELIVERY, Drug Delivery Systems, ONCOLYTIC DRUGS, Anthracyclines |
合成路线1
6-Aminocaproic acid (I) is condensed with maleic anhydride (II) in refluxing AcOH to provide maleimidocaproic acid (III). After activation of acid (III) as the corresponding mixed anhydride with isobutyl chloroformate, coupling with tert-butyl carbazate (IV) affords the N-Boc hydrazide (V). Subsequent acidic cleavage of the Boc group of (V) furnishes hydrazide (VI). Finally, hydrazide (VI) is condensed with doxorubicin (VII) to produce the title hydrazone conjugate.
| 【1】 Willner, D.; Trail, P.A.; Hofstead, S.J.; King, H.D.; Lasch, S.J.; Braslawsky, G.R.; Greenfield, R.S.; Kaneko, T.; Firestone, R.A.; (6-Maleimidocaproyl)hydrazone of doxorubicin - A new derivative for the preparation of immunoconjugates of doxorubicin. Bioconjugate Chem 1993, 4, 6, 521. |
| 【2】 Willner, D.; Trail, P.A.; King, D.H.; Hofstead, S.J.; Greenfield, R.S.; Braslawsky, G.R. (Bristol-Myers Squibb Co.); Thioether conjugates. EP 0554708; JP 1994025012; US 5622929 . |
| 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) | 41170 | 6-aminohexanoic acid | 60-32-2 | C6H13NO2 | 详情 | 详情 |
| (II) | 11182 | 2,5-Furandione; Maleic anhydride | 108-31-6 | C4H2O3 | 详情 | 详情 |
| (III) | 63203 | 6-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)hexanoic acid | C10H13NO4 | 详情 | 详情 | |
| (IV) | 10893 | tert-butyl 1-hydrazinecarboxylate; tert-butyl carbazate | 870-46-2 | C5H12N2O2 | 详情 | 详情 |
| (V) | 63204 | tert-butyl 2-[6-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)hexanoyl]-1-hydrazinecarboxylate | C15H23N3O5 | 详情 | 详情 | |
| (VI) | 63205 | 6-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)hexanohydrazide | C10H15N3O3 | 详情 | 详情 | |
| (VII) | 11675 | (8S,10S)-10-[[(2R,4S,5S,6S)-4-Amino-5-hydroxy-6-methyltetrahydro-2H-pyran-2-yl]oxy]-8-glycoloyl-6,8,11-trihydroxy-1-methoxy-7,8,9,10-tetrahydro-5,12-naphthacenedione | C27H29NO11 | 详情 | 详情 |