N²'-deacetyl-N²'-[4-methyl-4-(3-carboxy-3-sulfopropyldithio)-1-oxopentyl]maytansine | 1461704-01-7

• 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: N²'-deacetyl-N²'-[4-methyl-4-(3-carboxy-3-sulfopropyldithio)-1-oxopentyl]maytansine
• 英文别名: Soravtansine；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]-2-sulfobutanoic acid
• CAS: 1461704-01-7
• 化学式: C₄₂H₆₀ClN₃O₁₅S₃
• 分子量: 978.6
• InChiKey: GQSPYHXXAXFCRB-DSIKUUPMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  64
• 可旋转键数：
  16
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.64
• 拓扑面积：
  307
• 氢给体数：
  4
• 氢受体数：
  17

反应信息

• 作为产物：
  描述：

  DM4 、 N-succinimidyl 4-(2-pyridyldithio)-2-sulfobutanoate 以 aq. phosphate buffer 、 二甲基亚砜 为溶剂， 反应 36.0h， 以11%的产率得到N²'-deacetyl-N²'-[4-methyl-4-(3-carboxy-3-sulfopropyldithio)-1-oxopentyl]maytansine
  参考文献：
  名称：

  Metabolites of Antibody–Maytansinoid Conjugates: Characteristics andin VitroPotencies

  摘要：

  Several antibody-maytansinoid conjugates (AMCs) are in clinical trials for the treatment of various cancers. Each of these conjugates can be metabolized by tumor cells to give cytotoxic maytansinoid metabolites that can kill targeted cells. In preclinical studies in mice, the cytotoxic metabolites initially formed in vivo are further processed in the mouse liver to give several oxidized metabolic species. In this work, the primary AMC metabolites were synthesized and incubated with human liver microsomes (HLMs) to determine if human liver would likely give the same metabolites as those formed in mouse liver. The results of these HLM metabolism studies as well as the subsequent syntheses of the resulting HLM oxidation products are presented. Syntheses of the minor impurities formed during the conjugation of AMCs were also conducted to determine their cytotoxicities and to establish how these impurities would be metabolized by HLM.

  DOI：

  10.1021/mp5007757

文献信息

• Metabolites of Antibody–Maytansinoid Conjugates: Characteristics and<i>in Vitro</i>Potencies
  作者：Wayne Widdison、Sharon Wilhelm、Karen Veale、Juliet Costoplus、Gregory Jones、Charlene Audette、Barbara Leece、Laura Bartle、Yelena Kovtun、Ravi Chari

  DOI：10.1021/mp5007757

  日期：2015.6.1

  Several antibody-maytansinoid conjugates (AMCs) are in clinical trials for the treatment of various cancers. Each of these conjugates can be metabolized by tumor cells to give cytotoxic maytansinoid metabolites that can kill targeted cells. In preclinical studies in mice, the cytotoxic metabolites initially formed in vivo are further processed in the mouse liver to give several oxidized metabolic species. In this work, the primary AMC metabolites were synthesized and incubated with human liver microsomes (HLMs) to determine if human liver would likely give the same metabolites as those formed in mouse liver. The results of these HLM metabolism studies as well as the subsequent syntheses of the resulting HLM oxidation products are presented. Syntheses of the minor impurities formed during the conjugation of AMCs were also conducted to determine their cytotoxicities and to establish how these impurities would be metabolized by HLM.