N-methyl-N-[(2-methyldithio)-1-oxoethyl]-L-alanine | 138148-61-5

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: N-methyl-N-[(2-methyldithio)-1-oxoethyl]-L-alanine
• 英文别名: N-methyl-N-methyldithioacetoyl-L-alanine；N-methyl-N-methyldithioacetyl-L-alanine；L-Alanine, N-methyl-N-[(methyldithio)acetyl]-；(2S)-2-[methyl-[2-(methyldisulfanyl)acetyl]amino]propanoic acid
• CAS: 138148-61-5
• 化学式: C₇H₁₃NO₃S₂
• 分子量: 223.317
• InChiKey: RIRNEBWJRJDNNQ-YFKPBYRVSA-N

物化性质

• 沸点：
  379.3±27.0 °C(Predicted)
• 密度：
  1.302±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.4
• 重原子数：
  13
• 可旋转键数：
  5
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.71
• 拓扑面积：
  108
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  N-methyl-N-[(2-methyldithio)-1-oxoethyl]-L-alanine 、 maytansinol 在 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 zinc(II) chloride 作用下， 以 二氯甲烷 为溶剂， 生成 N^2'-deacetyl-N^2'-[2-(methyldithio)-1-oxoethyl]maytansine
  参考文献：
  名称：

  Ado-trastuzumab Emtansine (T-DM1): An Antibody–Drug Conjugate (ADC) for HER2-Positive Breast Cancer

  摘要：

  Ado-trastuzumab emtansine (T-DM1) is an antibody-drug conjugate that combines the antitumor properties of the humanized anti-human epidermal growth factor receptor 2 (HER2) antibody, trastuzumab, with the maytansinoid, DM1, a potent microtubule-disrupting agent, joined by a stable linker. Upon binding to HER2, the conjugate is internalized via receptor-mediated endocytosis, and an active derivative of DM1 is subsequently released by proteolytic degradation of the antibody moiety within the lysosome. Initial clinical evaluation led to a phase III trial in advanced HER2-positive breast cancer patients who had relapsed after prior treatment with trastuzumab and a taxane, which showed that T-DM1 significantly prolonged progression-free and overall survival with less toxicity than lapatinib plus capecitabine. In 2013, T-DM1 received FDA approval for the treatment of patients with HER2-positive metastatic breast cancer who had previously received trastuzumab and a taxane, separately or in combination, the first ADC to receive full approval based on a randomized study.

  DOI：

  10.1021/jm500766w
• 作为产物：
  描述：

  N-甲基-L-丙氨酸 、 H-hydroxysuccinimide ester of methyldithioacetic acid 在 三乙胺 作用下， 以 乙二醇二甲醚 、 水 为溶剂， 反应 2.0h， 生成 N-methyl-N-[(2-methyldithio)-1-oxoethyl]-L-alanine
  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 maytansinoids and their therapeutic use
  申请人：IMMUNOGEN INC

  公开号：EP0425235A2

  公开（公告）日：1991-05-02

  A cytotoxic agent comprising one or more maytansinoids linked to a cell binding agent. A therapeutic agent for killing selected cell populations comprising : (a) a cytotoxic amount of one or more maytansinoids linked to a cell binding agent, and (b) a pharmaceutically acceptable carrier, diluent or excipient. A method for killing selected cell populations comprising contacting a cell population or tissue suspected of containing cells from said selected cell population with a cytotoxic amount of a cytotoxic agent comprising one or more maytansinoids linked to a cell binding agent. An N-methyl-alanine-containing ester to maytansinol or an analogue of maytansinol, and N-methyl-alanine-containing ester comprising a linking group capable of linking an N-methyl-alanine-containing maytansinoid ester to a chemical moiety. N-methyl-cysteine-containing ester of maytansinol or an analogue of maytansinol.

  一种细胞毒性制剂，包括一种或多种与细胞结合剂连接的麦他霉素。一种用于杀死选定细胞群的治疗剂，包括：(a) 与细胞结合剂连接的一种或多种 maytansinoids 的细胞毒性量，和 (b) 医药上可接受的载体、稀释剂或赋形剂。一种杀死所选细胞群的方法，包括使细胞群或疑似含有所述所选细胞群的细胞的组织与细胞毒性量的细胞毒剂接触，该细胞毒剂包含一种或多种与细胞结合剂连接的麦他霉素。一种含 N-甲基丙氨酸的酯类到 maytansinol 或 maytansinol 的类似物，以及含 N-甲基丙氨酸的酯类，其包含的连接基团能够将含 N-甲基丙氨酸的 maytansinoid 酯类与化学分子连接起来。含 N-甲基半胱氨酸的 maytansinol 酯或 maytansinol 类似物。
• PROCESS FOR THE PREPARATION AND PURIFICATION OF THIOL-CONTAINING MAYTANSINOIDS
  申请人：Immunogen, Inc.

  公开号：EP1313738B1

  公开（公告）日：2005-12-21
• US5208020A
  申请人：——

  公开号：US5208020A

  公开（公告）日：1993-05-04
• US5416064A
  申请人：——

  公开号：US5416064A

  公开（公告）日：1995-05-16
• US6333410B1
  申请人：——

  公开号：US6333410B1

  公开（公告）日：2001-12-25