4-去乙酰基长春花碱 | 3352-69-0

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 长春花生物碱
• 中文名称: 4-去乙酰基长春花碱
• 中文别名: 长春新碱EP杂质E
• 英文名称: 4-O-des-acetyl vinblastine
• 英文别名: 4-deacetylvinblastine；vindesine；3,4-dihydroxy-15-(4-hydroxy-18-methoxycarbonyl-5,18-seco-ibogamin-18-yl)-16-methoxy-1-methyl-6,7-didehydro-aspidospermidine-3-carboxylic acid methyl ester；Desacetyl-vincaleukoblastin；Deacetylvincaleukoblastine；methyl (1R,9R,10S,11R,12R,19R)-12-ethyl-4-[(13S,15R,17S)-17-ethyl-17-hydroxy-13-methoxycarbonyl-1,11-diazatetracyclo[13.3.1.04,12.05,10]nonadeca-4(12),5,7,9-tetraen-13-yl]-10,11-dihydroxy-5-methoxy-8-methyl-8,16-diazapentacyclo[10.6.1.01,9.02,7.016,19]nonadeca-2,4,6,13-tetraene-10-carboxylate
• CAS: 3352-69-0
• 化学式: C₄₄H₅₆N₄O₈
• 分子量: 768.951
• InChiKey: NDMPLJNOPCLANR-XQLDGQACSA-N

物化性质

• 熔点：
  189-191°C
• 密度：
  1.39±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  56
• 可旋转键数：
  8
• 环数：
  9.0
• sp3杂化的碳原子比例：
  0.59
• 拓扑面积：
  148
• 氢给体数：
  4
• 氢受体数：
  11

制备方法与用途

Desacetylvinblastine is a prodrug of vinblastine and is used as an anticancer agent in the treatment of prostate cancer.

反应信息

• 作为反应物：
  描述：

  4-去乙酰基长春花碱 在 N-甲基吗啉 、 咪唑 、 palladium 10% on activated carbon 、 氢气 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 二氯甲烷 、 乙酸乙酯 、 N,N-二甲基甲酰胺 为溶剂， 反应 27.0h， 生成 (3aR,3a¹R,4R,5S,10bR)-methyl 4-(((5-((2-(2-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)ethoxy)ethyl)amino)-5-oxopentyl)(methyl)(phenyl)silyl)oxy)-3a-ethyl-9-((5S,7R,9S)-5-ethyl-5-hydroxy-9-(methoxycarbonyl)-2,4,5,6,7,8,9,10-octahydro-1H-3,7-methano[1]azacycloundecino[5,4-b]indol-9-yl)-5-hydroxy-8-methoxy-6-methyl-3a,3a¹4,5,5a,6,11,12-octahydro-1H-indolizino[8,1-cd]carbazole-5-carboxylate
  参考文献：
  名称：

  US2014/274951

  摘要：

  公开号：
• 作为产物：
  描述：

  (3aR,3a1R,4R,5S,5aR,10bR)-methyl 4-acetoxy-3a-ethyl-9-((3R,5S,7R,9S)-5-ethyl-5-hydroxy-9-(methoxycarbonyl)-2,4,5,6,7,8,9,10-octahydro-1H-3,7-methano[1]azacycloundecino[5,4-b]indol-9-yl)-5-hydroxy-8-methoxy-6-methyl-3a,3a1,4,5,5a,6,11,12-octahydro-1H-indolizino[8,1-cd]carbazole-5-carboxylate sulfuric acid 在 phosphate buffer 作用下， 以 甲醇 为溶剂， 反应 8.0h， 以95%的产率得到4-去乙酰基长春花碱
  参考文献：
  名称：

  Thimmaiah; Lloyd; Sethi, Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 1990, vol. 29, # 7, p. 678 - 680

  摘要：

  DOI：

文献信息

• ANTI-CANCER PHOSPHONATE ANALOGS
  申请人：Boojamra Constantine G.

  公开号：US20100022467A1

  公开（公告）日：2010-01-28

  The invention is related to phosphorus substituted anti-cancer compounds, compositions containing such compounds, and therapeutic methods that include the administration of such compounds, as well as to processes and intermediates useful for preparing such compounds.

  本发明涉及磷取代的抗癌化合物、含有这些化合物的组合物以及包括给予这些化合物的治疗方法，还涉及用于制备这些化合物的过程和中间体。
• Design and Synthesis of a Pro-Drug of Vinblastine Targeted at Treatment of Prostate Cancer with Enhanced Efficacy and Reduced Systemic Toxicity
  作者：Stephen F. Brady、Joseph M. Pawluczyk、Patricia K. Lumma、Dong-Mei Feng、Jenny M. Wai、Raymond Jones、Deborah DeFeo-Jones、Bradley K. Wong、Cynthia Miller-Stein、Jiunn H. Lin、Allen Oliff、Roger M. Freidinger、Victor M. Garsky

  DOI：10.1021/jm020139f

  日期：2002.10.1

  Chemotherapy of prostate cancer with antimitotic agents such as vinblastine and doxorubicin is only marginally effective, due to dose-limiting systemic toxicity. Herein we report the development of peptidyl conjugate 5 of the cytotoxic agent vinblastine (1), along with the results of its in vitro and in vivo evaluation as a pro-drug targeted at prostate cancer cells. Prostate-derived tumors are known to produce significant amounts of prostate specific antigen (PSA), a serine protease with chymotrypsin-like properties. Earlier work in these laboratories established that an appropriately engineered peptidyl pro-drug will release active cytotoxic agent strictly within the microenvironment of the tumor tissue (Garsky, V. M., et al. J. Med. Chem. 2001, 44, 4216-4224). Conjugate 5, which features an octapeptide segment attached by an ester linkage at the 4-position of vinblastine (1), undergoes rapid cleavage by PSA (T-1/2 = 12 min) between the Gln and Ser residues. In nude mouse xenograft studies, 5 reduced circulating PSA levels by 99% and tumor weight by 85% at a dose just below its MTD. By contrast, the putative end-point metabolite, the cytotoxic agent des-acetyl vinblastine (1b), was ineffective in reducing PSA levels and tumor burden at its maximum tolerated doses. Additional data from metabolism studies on 5 support the supervention of a novel in vivo processing mechanism, the spontaneous release of 1b from a dipeptidyl intermediate driven by favorable diketopiperazine formation.
• US7452901B2
  申请人：——

  公开号：US7452901B2

  公开（公告）日：2008-11-18
• US2014/274951
  申请人：——

  公开号：——

  公开（公告）日：——
• Thimmaiah; Lloyd; Sethi, Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 1990, vol. 29, # 7, p. 678 - 680
  作者：Thimmaiah、Lloyd、Sethi

  DOI：——

  日期：——