N^2'-deacetyl-N^2'-[4-methyl-4-(3-carboxy-propyldithio)-1-oxopentyl]maytansine | 905449-84-5

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 大环内酰胺类
• 英文名称: N^2'-deacetyl-N^2'-[4-methyl-4-(3-carboxy-propyldithio)-1-oxopentyl]maytansine
• 英文别名: N²'-deacetyl-N²'-[4-methyl-4-(3-carboxypropyldithio)-1-oxopentyl]maytansine；N2'-(4-((3-Carboxypropyl)dithio)-4-methyl-1-oxopentyl)-N2'-deacetylmaytansine；4-[[5-[[(2S)-1-[[(1S,2R,3S,5S,6S,16E,18E,20R,21S)-11-chloro-21-hydroxy-12,20-dimethoxy-2,5,9,16-tetramethyl-8,23-dioxo-4,24-dioxa-9,22-diazatetracyclo[19.3.1.110,14.03,5]hexacosa-10,12,14(26),16,18-pentaen-6-yl]oxy]-1-oxopropan-2-yl]-methylamino]-2-methyl-5-oxopentan-2-yl]disulfanyl]butanoic acid
• CAS: 905449-84-5
• 化学式: C₄₂H₆₀ClN₃O₁₂S₂
• 分子量: 898.536
• InChiKey: ORSKCTIDJPPMJJ-CYZHRDLYSA-N

物化性质

• 沸点：
  1041.4±65.0 °C(Predicted)
• 密度：
  1.33±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  60
• 可旋转键数：
  15
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.64
• 拓扑面积：
  244
• 氢给体数：
  3
• 氢受体数：
  14

反应信息

• 作为产物：
  描述：

  2,5-dioxopyrrolidin-1-yl 4-methyl-4-(methyldisulfanyl)pentanoate 在 乙二胺四乙酸 、 三乙胺 、 N,N'-二环己基碳二亚胺 、 zinc(II) chloride 、 1,4-二巯基-2,3-丁二醇 作用下， 以 甲醇 、 乙二醇二甲醚 、 phosphate buffer 、 乙醚 、 二氯甲烷 、 水 、 乙酸乙酯 为溶剂， 反应 10.0h， 生成 N^2'-deacetyl-N^2'-[4-methyl-4-(3-carboxy-propyldithio)-1-oxopentyl]maytansine
  参考文献：
  名称：

  Semisynthetic Maytansine Analogues for the Targeted Treatment of Cancer

  摘要：

  Maytansine, a highly cytotoxic natural product, failed as an anticancer agent in human clinical trials because of unacceptable systemic toxicity. The potent cell killing ability of maytansine can be used in a targeted delivery approach for the selective destruction of cancer cells. A series of new maytansinoids, bearing a disulfide or thiol substituent were synthesized. The chain length of the ester side chain and the degree of steric hindrance on the carbon atom bearing the thiol substituent were varied. Several of these maytansinoids were found to be even more potent in vitro than maytansine. The targeted delivery of these maytansinoids, using monoclonal antibodies, resulted in a high, specific killing of the targeted cells in vitro and remarkable antitumor activity in vivo.

  DOI：

  10.1021/jm060319f

文献信息

• Semisynthetic Maytansine Analogues for the Targeted Treatment of Cancer
  作者：Wayne C. Widdison、Sharon D. Wilhelm、Emily E. Cavanagh、Kathleen R. Whiteman、Barbara A. Leece、Yelena Kovtun、Victor S. Goldmacher、Hongsheng Xie、Rita M. Steeves、Robert J. Lutz、Robert Zhao、Lintao Wang、Walter A. Blättler、Ravi V. J. Chari

  DOI：10.1021/jm060319f

  日期：2006.7.1

  Maytansine, a highly cytotoxic natural product, failed as an anticancer agent in human clinical trials because of unacceptable systemic toxicity. The potent cell killing ability of maytansine can be used in a targeted delivery approach for the selective destruction of cancer cells. A series of new maytansinoids, bearing a disulfide or thiol substituent were synthesized. The chain length of the ester side chain and the degree of steric hindrance on the carbon atom bearing the thiol substituent were varied. Several of these maytansinoids were found to be even more potent in vitro than maytansine. The targeted delivery of these maytansinoids, using monoclonal antibodies, resulted in a high, specific killing of the targeted cells in vitro and remarkable antitumor activity in vivo.