4-((9-fluorenylmethoxy)carboxamido)phenylacetic acid N-hydroxysuccinimidate | 147227-80-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 芴
• 英文名称: 4-((9-fluorenylmethoxy)carboxamido)phenylacetic acid N-hydroxysuccinimidate
• 英文别名: (2,5-dioxopyrrolidin-1-yl) 2-[4-(9H-fluoren-9-ylmethoxycarbonylamino)phenyl]acetate
• CAS: 147227-80-3
• 化学式: C₂₇H₂₂N₂O₆
• 分子量: 470.481
• InChiKey: ITUNZLDXBVJCPQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  35
• 可旋转键数：
  8
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  102
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  4-((9-fluorenylmethoxy)carboxamido)phenylacetic acid N-hydroxysuccinimidate 在 吗啉 、 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 21.0h， 生成 N-(4-aminophenylacetyl)doxorubicin
  参考文献：
  名称：

  Prodrugs of doxorubicin and melphalan and their activation by a monoclonal antibody-penicillin-G amidase conjugate

  摘要：

  The syntheses and cytotoxic activities of substituted N-phenylacetamido derivatives of doxorubicin and melphalan are described. The derivatives were designed as prodrugs which could be activated in a site-specific manner by monoclonal antibody-penicillin-G amidase (mAb-PGA) conjugates. N-(Phenylacetamido)doxorubicin (2) and N-(phenylacetyl)melphalan (6) were found to be 10- and 20-fold less cytotoxic against H2981 lung adenocarcinoma cells than doxorubicin and melphalan, respectively. When incubated with PGA, the cytotoxicity of 2 and 6 increased and became equivalent to that of the corresponding drugs from which they were made. The poor solubility characteristics of 2 in aqueous solutions provided the basis for the development of the more soluble doxorubicin derivatives, N-(4-aminophenylacetyl)doxorubicin (3) and N-(4-phosphonooxy)phenylacetyl)-doxorubicin (4). In vitro cytotoxicity assays indicated that 3 and 4 were at least 1000-fold less toxic than doxorubicin against H2981 cells. PGA and the mAb conjugate L6-PGA were able to effect the activation of 3 and 6 on H2981 cells (L6-antigen positive). Hydrolysis of the phosphate group of 4 was required prior to activation with PGA or L6-PGA. This was achieved using alkaline phosphatase, or by exposing 4 to phosphatases present in cell culture medium. The activation of 3, 4, and 6 on H2981 cells by L6-PGA occurred in an immunologically specific manner, since activation could be blocked by saturating cell surface antigens with L6 prior to treatment with L6-PGA. These results demonstrate that 3, 4, and 6 are prodrugs that can be specifically activated to release clinically approved anticancer agents by a mAb-PGA conjugate.

  DOI：

  10.1021/jm00059a018
• 作为产物：
  描述：

  N,N'-二琥珀酰亚胺基碳酸酯 、 Sodium; [4-(9H-fluoren-9-ylmethoxycarbonylamino)-phenyl]-acetate 以 N,N-二甲基甲酰胺 为溶剂， 反应 1.0h， 以57%的产率得到4-((9-fluorenylmethoxy)carboxamido)phenylacetic acid N-hydroxysuccinimidate
  参考文献：
  名称：

  Prodrugs of doxorubicin and melphalan and their activation by a monoclonal antibody-penicillin-G amidase conjugate

  摘要：

  The syntheses and cytotoxic activities of substituted N-phenylacetamido derivatives of doxorubicin and melphalan are described. The derivatives were designed as prodrugs which could be activated in a site-specific manner by monoclonal antibody-penicillin-G amidase (mAb-PGA) conjugates. N-(Phenylacetamido)doxorubicin (2) and N-(phenylacetyl)melphalan (6) were found to be 10- and 20-fold less cytotoxic against H2981 lung adenocarcinoma cells than doxorubicin and melphalan, respectively. When incubated with PGA, the cytotoxicity of 2 and 6 increased and became equivalent to that of the corresponding drugs from which they were made. The poor solubility characteristics of 2 in aqueous solutions provided the basis for the development of the more soluble doxorubicin derivatives, N-(4-aminophenylacetyl)doxorubicin (3) and N-(4-phosphonooxy)phenylacetyl)-doxorubicin (4). In vitro cytotoxicity assays indicated that 3 and 4 were at least 1000-fold less toxic than doxorubicin against H2981 cells. PGA and the mAb conjugate L6-PGA were able to effect the activation of 3 and 6 on H2981 cells (L6-antigen positive). Hydrolysis of the phosphate group of 4 was required prior to activation with PGA or L6-PGA. This was achieved using alkaline phosphatase, or by exposing 4 to phosphatases present in cell culture medium. The activation of 3, 4, and 6 on H2981 cells by L6-PGA occurred in an immunologically specific manner, since activation could be blocked by saturating cell surface antigens with L6 prior to treatment with L6-PGA. These results demonstrate that 3, 4, and 6 are prodrugs that can be specifically activated to release clinically approved anticancer agents by a mAb-PGA conjugate.

  DOI：

  10.1021/jm00059a018

文献信息

• Radiolabeled platelet GPIIb/IIIa receptor antagonists as imaging agents for the diagnosis of thromboembolic disorders
  申请人：Dupont Pharmaceuticals Company

  公开号：EP0995761A2

  公开（公告）日：2000-04-26

  This invention provides novel radiopharmaceuticals that are radiolabeled cyclic compounds containing carbocyclic or heterocyclic ring systems which act as antagonists of the platelet glycoprotein IIb/IIIa complex; to the methods of using said radiopharmaceuticals as imaging agents for the diagnosis of arterial and venous thrombi; to novel reagents for the preparation of said radiopharmaceuticals; and to kits comprising said reagents.

  本发明提供了新型放射性药物，它们是含有碳环或杂环环系统的放射性标记环状化合物，可作为血小板糖蛋白 IIb/IIIa 复合物的拮抗剂；提供了将所述放射性药物用作诊断动脉和静脉血栓的成像剂的方法；提供了制备所述放射性药物的新型试剂；以及提供了包含所述试剂的试剂盒。
• RADIOLABELED PLATELET GPIIb/IIIa RECEPTOR ANTAGONISTS AS IMAGING AGENTS FOR THE DIAGNOSIS OF THROMBOEMBOLIC DISORDERS
  申请人：Dupont Pharmaceuticals Company

  公开号：EP0692982B1

  公开（公告）日：2000-07-05
• EP0692982A4
  申请人：——

  公开号：EP0692982A4

  公开（公告）日：1998-03-11
• US5879657A
  申请人：——

  公开号：US5879657A

  公开（公告）日：1999-03-09
• US6022523A
  申请人：——

  公开号：US6022523A

  公开（公告）日：2000-02-08