N²'-deacetyl N²'-[4-[[4-[[(1S)-2-amino-1-carboxypentyl]amino]-4-oxobutyl]dithio]-4-methyl-1-oxopentyl]maytansine | 1280215-91-9

• 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: N²'-deacetyl N²'-[4-[[4-[[(1S)-2-amino-1-carboxypentyl]amino]-4-oxobutyl]dithio]-4-methyl-1-oxopentyl]maytansine
• 英文别名: lysine-Nε-SPDB-DM4；DM4-spdb-L-lysine；(2S)-2-amino-6-[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]butanoylamino]hexanoic acid
• CAS: 1280215-91-9
• 化学式: C₄₈H₇₂ClN₅O₁₃S₂
• 分子量: 1026.71
• InChiKey: VUAUZOXSQKWNNO-NBSRGMMNSA-N

物化性质

• 沸点：
  1158.3±65.0 °C(Predicted)
• 密度：
  1.32±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  69
• 可旋转键数：
  21
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  300
• 氢给体数：
  5
• 氢受体数：
  16

反应信息

• 作为产物：
  描述：

  5-二氧代吡咯烷-1-基4-(吡啶-2-基二硫烷基)丁酸乙酯 、 DM4 、 L-赖氨酸盐酸盐 以 aq. phosphate buffer 、 N,N-二甲基乙酰胺 为溶剂， 反应 4.0h， 以29%的产率得到N²'-deacetyl N²'-[4-[[4-[[(1S)-2-amino-1-carboxypentyl]amino]-4-oxobutyl]dithio]-4-methyl-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