4-(methyldithio)pentanoic acid | 796073-58-0

• 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: 4-(methyldithio)pentanoic acid
• 英文别名: 4-(Methyldisulfanyl)pentanoic acid；4-(methyldisulfanyl)pentanoic acid
• CAS: 796073-58-0
• 化学式: C₆H₁₂O₂S₂
• 分子量: 180.292
• InChiKey: NPNVMXJRUIQMRE-UHFFFAOYSA-N

物化性质

• 沸点：
  307.3±25.0 °C(Predicted)
• 密度：
  1?+-.0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  10
• 可旋转键数：
  5
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.83
• 拓扑面积：
  87.9
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-(methyldithio)pentanoic acid 在 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 、 N,N'-二环己基碳二亚胺 、 zinc(II) chloride 作用下， 以 乙二醇二甲醚 、 乙醚 、 二氯甲烷 、 水 为溶剂， 反应 6.0h， 生成 N^2'-deacetyl-N^2'-[4-(R,S)-(methyldithio)-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
• 作为产物：
  描述：

  甲基硫代磺酸甲酯 在 sodium carbonate 作用下， 以 水 、 乙醇 为溶剂， 以45%的产率得到4-(methyldithio)pentanoic acid
  参考文献：
  名称：

  Cytotoxic agents comprising new maytansinoids

  摘要：

  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。

  公开号：

  US20040235840A1

文献信息

• [EN] NOVEL CYTOTOXIC AGENTS AND CONJUGATES THEREOF<br/>[FR] NOUVEAUX AGENTS CYTOTOXIQUES ET LEURS CONJUGUÉS
  申请人：POLYTHERICS LTD

  公开号：WO2018051109A1

  公开（公告）日：2018-03-22

  Provided herein are novel maytansinoid compounds of general formula I. Also provided herein are conjugates comprising the compounds linked to a binding protein via a linker, and conjugating reagents comprising the compounds attached via a linker to at least one functional group capable of reacting with a binding protein. Also provided herein are pharmaceutical compositions comprising the compounds and conjugates, therapeutic methods and uses involving the compounds and conjugates, for example in cancer therapy, and novel synthetic processes.

  本文提供了一般式I的新型马丹西酮类化合物。本文还提供了将这些化合物通过连接剂连接到结合蛋白上的共轭物，以及将这些化合物通过连接剂连接到至少一个能与结合蛋白发生反应的功能基团的共轭试剂。本文还提供了包含这些化合物和共轭物的药物组合物，涉及这些化合物和共轭物的治疗方法和用途，例如在癌症治疗中，并提供了新的合成过程。
• CYTOTOXIC AGENTS COMPRISING NEW MAYTANSINOIDS
  申请人：Chari V. J. Ravi

  公开号：US20070264266A1

  公开（公告）日：2007-11-15

  New thiol and disulfide-containing maytansinoids bearing a mono or di-alkyl substitution on the α-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.

  公开了一种新的含有巯基和二硫键的马丹霉素衍生物，其α-碳原子上带有硫原子的位置上具有单烷基或双烷基取代。还公开了制备这些新马丹霉素衍生物的方法以及将这些新马丹霉素衍生物与细胞结合剂连接的方法。马丹霉素-细胞结合剂共轭物作为治疗剂具有特异性地传递到目标细胞并具有细胞毒性。与先前描述的药物相比，这些共轭物在动物肿瘤模型中显示出极大的治疗效果。
• CYTOTOXIC AGENTS COMPRISING NEW MAYTANSINOIDS (DM4)
  申请人：ImmunoGen, Inc.

  公开号：US20150071949A1

  公开（公告）日：2015-03-12

  New thiol and disulfide-containing maytansinoids bearing a mono or di-alkyl substitution on the α-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.

  本文介绍了一种新的含巯基和二硫键的马丹霉素衍生物，其α-碳原子上的硫原子带有单烷基或双烷基取代基。同时，还揭示了合成这些新马丹霉素衍生物和将其与细胞结合剂连接的方法。马丹霉素-细胞结合剂结合物可作为治疗剂，专门传递到靶细胞并具有细胞毒性。与先前描述的治疗剂相比，这些结合物在动物肿瘤模型中显示出极大的治疗效果。
• MAYTANSINOID-CELL-BINDING AGENT CONJUGATES
  申请人：ImmunoGen, Inc.

  公开号：EP3851126A1

  公开（公告）日：2021-07-21

  New thiol and disulfide-containing maytansinoids bearing a mono or di-alkyl substitution on the α-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.

  本发明公开了在含硫原子的α-碳原子上具有单烷基或二烷基取代的新的含硫醇和二硫化物的类 maytansinoids。此外，还公开了合成这些新的 maytansinoids 的方法以及将这些新的 maytansinoids 与细胞结合剂连接的方法。这种 maytansinoids-细胞结合剂共轭物可用作治疗剂，能特异性地输送到靶细胞并具有细胞毒性。与之前描述的药物相比，这些共轭物在动物肿瘤模型中的疗效大大提高。
• Cytotoxic agents and conjugates thereof
  申请人：POLYTHERICS LIMITED

  公开号：US10654873B2

  公开（公告）日：2020-05-19

  Provided herein are novel maytansinoid compounds of general formula I. Also provided herein are conjugates comprising the compounds linked to a binding protein via a linker, and conjugating reagents comprising the compounds attached via a linker to at least one functional group capable of reacting with a binding protein. Also provided herein are pharmaceutical compositions comprising the compounds and conjugates, therapeutic methods and uses involving the compounds and conjugates, for example in cancer therapy, and novel synthetic processes.

  本文提供了通式 I 的新型 maytansinoid 化合物。本文还提供了包含通过连接体与结合蛋白连接的化合物的共轭物，以及包含通过连接体与至少一个能与结合蛋白反应的官能团连接的化合物的共轭试剂。本文还提供了包含化合物和共轭物的药物组合物、涉及化合物和共轭物的治疗方法和用途（例如在癌症治疗中）以及新型合成工艺。