4-(甲基二硫烷基)丁酸 | 138148-60-4

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 中文名称: 4-(甲基二硫烷基)丁酸
• 英文名称: 4-(methyldithio)butanoic acid
• 英文别名: 4-methyldithio-butanoic acid；4-methyldithiobutanoic acid；Butanoic acid, 4-(methyldithio)-；4-(methyldisulfanyl)butanoic acid
• CAS: 138148-60-4
• 化学式: C₅H₁₀O₂S₂
• 分子量: 166.265
• InChiKey: CXRDNLDONYMEBK-UHFFFAOYSA-N

物化性质

• 沸点：
  303.5±25.0 °C(Predicted)
• 密度：
  1.244±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  9
• 可旋转键数：
  5
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.8
• 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-(甲基二硫烷基)丁酸 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 [(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] (2R)-2-[methyl-[4-(methyldisulfanyl)butanoyl]amino]propanoate
  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 、 3-羧丙基二硫化物 在 sodium hydroxide 、 1,4-二巯基-2,3-丁二醇 作用下， 以 甲醇 、 水 为溶剂， 反应 3.0h， 以56%的产率得到4-(甲基二硫烷基)丁酸
  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：US05208020A1

  公开（公告）日：1993-05-04

  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 of maytansinol or an analogue of maytansinol, said 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.

  一种细胞毒性剂，包括与细胞结合剂连接的一种或多种梅坦西酮类化合物。一种用于杀灭选定细胞群体的治疗剂，包括：(a) 与细胞结合剂连接的一种或多种梅坦西酮类化合物的细胞毒性量，以及(b) 一种药用可接受的载体稀释剂或赋形剂。一种用于杀灭选定细胞群体的方法，包括将疑似含有来自所述选定细胞群体的细胞的细胞群体或组织与包括与细胞结合剂连接的一种或多种梅坦西酮类化合物的细胞毒性剂的细胞毒性量接触。一种甲基-丙氨酸酯基梅坦西酮或梅坦西酮类似物，所述甲基-丙氨酸酯基包括一种能够将甲基-丙氨酸酯基梅坦西酮与化学基团连接的连接基团。梅坦西酮的甲基-半胱氨酸酯基或梅坦西酮类似物。
• Process for the preparation and purification of thiol-containing maytansinoids
  申请人：Immunogen, Inc.

  公开号：US06333410B1

  公开（公告）日：2001-12-25

  The present invention provides a process for the preparation and purification of thiol-containing maytansinoids comprising the steps of: (1) reductive hydrolysis of a maytansinoid C-3 ester with a reducing agent selected from the group consisting lithium trimethoxyaluminum hydride (LiAl(OMe)3H), lithium triethoxyaluminum hydride (LiAl(OEt)3H), lithium tripropoxyaluminum hydride (LiAl(OPr)3H), sodium trimethoxyaluminum hydride (NaAl(OMe)3H), sodium triethoxyaluminum hydride (NaAl(OEt)3H) and sodium tripropoxyaluminum hydride (NaAl(OPr)3H) to yield a maytansinol; (2) purifying the maytansinol to remove side products when present; (3) esterifying the purified maytansinol with a carboxylic acid to yield a mixture of an L- and a D-aminoacyl ester of maytansinol; (4) separating the L-aminoacyl ester of maytansinol from the reaction mixture in (3); (5) reducing the L-aminoacyl ester of maytansinol to yield a thiol-containing maytansinoid; and (6) purifying the thiol-containing maytansinoid.

  本发明提供了一种制备和纯化含硫醇马坦西酮类化合物的方法，包括以下步骤：(1) 使用选择自锂三甲氧基铝氢化物（LiAl(OMe)3H）、锂三乙氧基铝氢化物（LiAl(OEt)3H）、锂三异丙氧基铝氢化物（LiAl(OPr)3H）、钠三甲氧基铝氢化物（NaAl(OMe)3H）、钠三乙氧基铝氢化物（NaAl(OEt)3H）和钠三异丙氧基铝氢化物（NaAl(OPr)3H）的还原剂对马坦西酮类化合物C-3酯进行还原水解，得到马坦西醇；(2) 纯化马坦西醇以去除可能存在的副产物；(3) 将纯化的马坦西醇与羧酸酯化，得到马坦西醇的L-和D-氨基酰酯混合物；(4) 从步骤(3)中的反应混合物中分离出马坦西醇的L-氨基酰酯；(5) 将马坦西醇的L-氨基酰酯还原，得到含硫醇的马坦西酮类化合物；(6) 纯化含硫醇的马坦西酮类化合物。
• Cytotoxic agents comprising new C-2 modified taxanes
  申请人：Aventis Pharma S.A.

  公开号：EP1688415A1

  公开（公告）日：2006-08-09

  The present invention relates to novel cytotoxic agents and their therapeutic use. More specifically, the invention relates to novel cytotoxic agents comprising taxanes and their therapeutic use. These novel cytotoxic agents have therapeutic use as a result of delivering the taxanes to a specific cell population in a targeted fashion by chemically linking the taxane to a cell binding agent.

  本发明涉及新型细胞毒性剂及其治疗应用。更具体地，本发明涉及包括紫杉醇的新型细胞毒性剂及其治疗应用。这些新型细胞毒性剂具有治疗用途，因为它们通过将紫杉醇化学连接到细胞结合剂，以有针对性的方式将紫杉醇传递到特定的细胞群体。
• Cytotoxic agents comprising new taxanes
  申请人：Aventis Pharma S.A.

  公开号：EP1669358A1

  公开（公告）日：2006-06-14

  The present invention relates to novel cytotoxic agents and their therapeutic use. More specifically, the invention relates to novel cytotoxic agents comprising taxanes and their therapeutic use. These novel cytotoxic agents have therapeutic use as a result of delivering the taxanes to a specific cell population in a targeted fashion by chemically linking the taxane to a cell binding agent.

  本发明涉及新型细胞毒性药剂及其治疗用途。更具体地说，本发明涉及包含紫杉醇的新型细胞毒性药剂及其治疗用途。这些新型细胞毒性药剂具有治疗用途，因为通过化学连接细胞结合剂将紫杉醇传递到特定的细胞群体，以有针对性的方式靶向治疗。
• Synthetic and computational investigation of neighboring group participation by a nucleophilic disulfide bond
  作者：Takuhei Yamamoto、Koki Fukuta、Yuki Kariya、Taiki Matsuura、Hiroaki Hagiwara、Bunji Uno、Yukihiro Esaka

  DOI：10.1039/d2ob01574a

  日期：——

  Disulfide bonds of 2-isocyanatophenyl methyl disulfide and 2-endo-isocyanato-6-endo-(methyldisulfanyl)bicyclo[2.2.1]heptane showed neighboring group participation in the formation of thiocarbamates. Natural Bond Orbital (NBO) analyses revealed that the unusual nucleophilicity requires a rigid through-space interaction between a lone pair of the disulfide bond and an antibonding orbital of isocyanate

  2-isocyanatophenyl methyl disulfide 和 2- endo -isocyanato -6- endo- (methyldisulfanyl)bicyclo[2.2.1]heptane 的二硫键显示相邻基团参与了硫代氨基甲酸酯的形成。自然键轨道 (NBO) 分析表明，不寻常的亲核性需要孤对二硫键和异氰酸酯的反键轨道之间存在刚性的空间相互作用。