3-Hydroxymethyl-8-oxo-7-phenylacetylamino-5-thia-1-aza-bicyclo[4.2.0]oct-2-ene-2-carboxylic acid benzhydryl ester | 35246-64-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 内酰胺类
• 英文名称: 3-Hydroxymethyl-8-oxo-7-phenylacetylamino-5-thia-1-aza-bicyclo[4.2.0]oct-2-ene-2-carboxylic acid benzhydryl ester
• 英文别名: Benzhydryl 3-(hydroxymethyl)-8-oxo-7-[(2-phenylacetyl)amino]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate
• CAS: 35246-64-1
• 化学式: C₂₉H₂₆N₂O₅S
• 分子量: 514.602
• InChiKey: YLOQFPCGJCRAPQ-UHFFFAOYSA-N

物化性质

• 熔点：
  174.5-176 °C(Solv: ethyl acetate (141-78-6); hexane (110-54-3))
• 沸点：
  810.3±65.0 °C(Predicted)
• 密度：
  1.40±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  37
• 可旋转键数：
  9
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  121
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  7-[(2-phenylacetyl)amino]-3-hydroxymethyl cephalosporanic acid 、 N,N'-diisopropyl-O-benzhydrylisourea 以 四氢呋喃 为溶剂， 反应 2.0h， 以50%的产率得到3-Hydroxymethyl-8-oxo-7-phenylacetylamino-5-thia-1-aza-bicyclo[4.2.0]oct-2-ene-2-carboxylic acid benzhydryl ester
  参考文献：
  名称：

  N,N'-Diisopropyl-O-Diphenylmethyl Isourea: A Mild and Convenient Alkylating Agent for the Formation of Cephalosporin Derivatives

  摘要：

  N,N'-Diisopropyl-O-diphenylmethyl isourea reacts with cephalosporin-4-carboxylic acid in tetrahydrofuran at room temperature to give the diphenylmethyl (DPM) ester in good yields without isomerization of the double bond from C-3 to C-2.

  DOI：

  10.1080/00397919808007035

文献信息

• Prodrugs for beta-lactamase and uses thereof
  申请人：Bristol-Myers Squibb Company

  公开号：EP0484870A2

  公开（公告）日：1992-05-13

  The instant invention relates to a novel method for the delivery of antitumor drugs to tumor cells by the administration of a tumor-selective antibody- β-lactamase conjugate that binds to tumor cells, and the additional administration of a cephalosporin prodrug that is converted at the tumor site, in the presence of the antibody-β-lactamase, to an active cytotoxic drug. According to the preferred embodiment of this invention, a cephalosporin mustard has been constructed which when cleaved by β-lactamase yields a cytotoxic nitrogen mustard. The methods, antibody-enzyme conjugate, prodrugs, pharmaceutical compositions, and combinations of this invention provide for enhanced selective killing of tumor cells and are thus useful in the treatment of cancers and other tumors.

  本发明涉及一种向肿瘤细胞递送抗肿瘤药物的新方法，该方法是通过给药与肿瘤细胞结合的肿瘤选择性抗体-β-内酰胺酶共轭物，以及额外给药头孢菌素原药，在抗体-β-内酰胺酶存在的情况下，该原药在肿瘤部位转化为活性细胞毒性药物。根据本发明的优选实施方案，已经构建了一种头孢菌素芥子气，当它被β-内酰胺酶裂解时，会产生一种具有细胞毒性的氮芥。本发明的方法、抗体-酶结合物、原药、药物组合物和组合物可增强对肿瘤细胞的选择性杀伤，因此可用于治疗癌症和其他肿瘤。