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【结 构 式】 
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【分子编号】53674 【品名】9H-fluoren-9-ylmethyl 5-{(2S,4R)-2-[(3S,6S,9S,12S,15S,18S)-12-(3-amino-3-oxopropyl)-9-cyclohexyl-18-{[((2S,3S,4S,6R)-6-{[(1S,3S)-3-glycoloyl-3,5,12-trihydroxy-10-methoxy-6,11-dioxo-1,2,3,4,6,11-hexahydro-1-naphthacenyl]oxy}-3-hydroxy-2-methyltetrahydro-2H-pyran-4-yl)amino]carbonyl}-6,15-bis(hydroxymethyl)-3,20-dimethyl-4,7,10,13,16-pentaoxo-2,5,8,11,14,17-hexaazahenicos-1-anoyl]-4-hydroxypyrrolidinyl}-5-oxopentanoate 【CA登记号】n/a |
【 分 子 式 】C79H99N9O25 【 分 子 量 】1574.70072 【元素组成】C 60.26% H 6.34% N 8.01% O 25.4% |
合成路线1
该中间体在本合成路线中的序号：(XIX)Coupling of peptide (XVII) to the amino group of doxorubicin (XVIII) using DPPA yielded amide (XIX). Alternatively, EDC in the presence of HOAt can be used as the coupling reagent. The fluorenylmethyl ester of (XIX) was finally removed by treatment with piperidine in DMF to produce the title compound.
| 【2】 Garsky, V.M.; Feng, D.-M.; DeFeo-Jones, D. (Merck & Co., Inc.); Conjugates useful in the treatment of prostate cancer. JP 2000509407; WO 9818493 . |
| 【3】 Oliff, A.I.; Jones, R.E.; Defeo-Jones, D. (Merck & Co., Inc.); A method of treating cancer. WO 0059930 . |
| 【4】 Kaufman, M.J.; Almarsson, O.; Nerurkar, M.J.; Lynch, J.E.; Karki, S.B.; Cameron, M.; Lieberman, D.R.; Robbins, M.A.; Shi, Y.-J. (Merck & Co., Inc.); Salt form of a conjugate useful in the treatment of prostate cancer. US 6355611; WO 0130804 . |
| 【1】 Feng, D.-M.; Wai, J.; Ramjit, H.G.; Sardana, M.K.; Lumma, P.K.; DeFeo-Jones, D.; Jones, R.E.; Freidinger, R.M.; Oliff, A.; Garsky, V.M.; The synthesis of a prodrug of doxorubicin designed to provide reduced systemic toxicity and greater target efficacy. J Med Chem 2001, 44, 24, 4216. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XVII) | 53673 | (3S,6S,9S,12S,15S,18S)-12-(3-amino-3-oxopropyl)-9-cyclohexyl-1-{(2S,4R)-1-[5-(9H-fluoren-9-ylmethoxy)-5-oxopentanoyl]-4-hydroxypyrrolidinyl}-6,15-bis(hydroxymethyl)-18-isobutyl-3-methyl-1,4,7,10,13,16-hexaoxo-2,5,8,11,14,17-hexaazanonadecan-19-oic acid | n/a | C52H72N8O15 | 详情 | 详情 |
| (XVIII) | 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 | |
| (XIX) | 53674 | 9H-fluoren-9-ylmethyl 5-{(2S,4R)-2-[(3S,6S,9S,12S,15S,18S)-12-(3-amino-3-oxopropyl)-9-cyclohexyl-18-{[((2S,3S,4S,6R)-6-{[(1S,3S)-3-glycoloyl-3,5,12-trihydroxy-10-methoxy-6,11-dioxo-1,2,3,4,6,11-hexahydro-1-naphthacenyl]oxy}-3-hydroxy-2-methyltetrahydro-2H-pyran-4-yl)amino]carbonyl}-6,15-bis(hydroxymethyl)-3,20-dimethyl-4,7,10,13,16-pentaoxo-2,5,8,11,14,17-hexaazahenicos-1-anoyl]-4-hydroxypyrrolidinyl}-5-oxopentanoate | n/a | C79H99N9O25 | 详情 | 详情 |