R-4-mercaptopentanoic acid | 796073-77-3

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: R-4-mercaptopentanoic acid
• 英文别名: Pentanoic acid, 4-mercapto-, (4R)-；(4R)-4-sulfanylpentanoic acid
• CAS: 796073-77-3
• 化学式: C₅H₁₀O₂S
• 分子量: 134.199
• InChiKey: NEAFWRKPYYJETG-SCSAIBSYSA-N

物化性质

• 沸点：
  256.1±23.0 °C(Predicted)
• 密度：
  1.117±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  8
• 可旋转键数：
  3
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.8
• 拓扑面积：
  38.3
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  R-4-mercaptopentanoic acid 在 NaH₂PO₃ buffer 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 为溶剂， 反应 4.5h， 生成 (2,5-dioxopyrrolidin-1-yl) (4R)-4-(methyldisulfanyl)pentanoate
  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
• 作为产物：
  描述：

  S-3-O-p-toluenesulfonyl-pentanenitrile 在 sodium hydroxide 作用下， 以 乙醇 、 水 为溶剂， 生成 R-4-mercaptopentanoic acid
  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

• Cytotoxic agents comprising new maytansinoids
  申请人：IMMUNOGEN, INC.

  公开号：US20040235840A1

  公开（公告）日：2004-11-25

  New thiol and disulfide-containing maytansinoids bearing a mono or di-alkyl substitution on the &agr;-carbon atom bearing the sulfur atom are disclosed. Also disclosed are methods for the synthesis of these new maytansinoids and methods for the linkage of these new maytansinoids to cell-binding agents. The maytansinoid-cell-binding agent conjugates are useful as therapeutic agents, which are delivered specifically to target cells and are cytotoxic. These conjugates display vastly improved therapeutic efficacy in animal tumor models compared to the previously described agents.

  揭示了具有α-碳原子上带有硫原子的单烷基或双烷基取代基的新硫醇和二硫化物含有马坦西诺伊德。还公开了合成这些新马坦西诺伊德的方法以及将这些新马坦西诺伊德连接到细胞结合剂的方法。马坦西诺伊德-细胞结合剂结合物可用作治疗剂，专门传递到靶细胞并具有细胞毒性。与先前描述的药物相比，这些结合物在动物肿瘤模型中显示出大大改善的治疗效果。
• 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.