13-debromo-13-iodoagelastatin A | 1613128-33-8

• 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: 13-debromo-13-iodoagelastatin A
• 英文别名: (1R,9S,10S,14S)-14-hydroxy-3-iodo-13-methyl-2,8,11,13-tetrazatetracyclo[7.6.0.02,6.010,14]pentadeca-3,5-diene-7,12-dione
• CAS: 1613128-33-8
• 化学式: C₁₂H₁₃IN₄O₃
• 分子量: 388.165
• InChiKey: ZXFWJADVBRPYSU-WJOUQXRDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.6
• 重原子数：
  20
• 可旋转键数：
  0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  86.6
• 氢给体数：
  3
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  debromoagelastatin A 在 N-碘代丁二酰亚胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 36.0h， 以21%的产率得到13-debromo-13-iodoagelastatin A
  参考文献：
  名称：

  Potent Fluorinated Agelastatin Analogues for Chronic Lymphocytic Leukemia: Design, Synthesis, and Pharmacokinetic Studies

  摘要：

  Chronic lymphocytic leukemia (CLL) is the most common lymphoid neoplasia in Western societies and is currently incurable. Multiple treatment options are practiced, but the available small molecule drugs suffer from dose-limiting toxicity and undesirable side effects. The need for new, less toxic treatments is a pressing concern. Here, we demonstrate that (-)-agelastatin A (1a), a pyrrole-imidazole alkaloid obtained from a marine sponge, exhibits potent in vitro activity against primary cell lines of CLL and disclose the synthesis of several analogues that are equipotent or exceed the potency of the natural product. The novel synthetic analogue, 13-debromo-13-trifluoromethyl agelastatin A (1j), showed higher activity than the natural product when tested against the same cell lines and is the most potent agelastatin derivative reported to date. A detailed in vitro structure-activity relationship of 1a in CLL compared to that of 22 synthetic analogues is described along with preliminary in vivo pharmacokinetic and metabolism studies on the most potent compounds.

  DOI：

  10.1021/jm4016922

文献信息

• Potent Fluorinated Agelastatin Analogues for Chronic Lymphocytic Leukemia: Design, Synthesis, and Pharmacokinetic Studies
  作者：E. Paige Stout、Michael Y. Choi、Januario E. Castro、Tadeusz F. Molinski

  DOI：10.1021/jm4016922

  日期：2014.6.26

  Chronic lymphocytic leukemia (CLL) is the most common lymphoid neoplasia in Western societies and is currently incurable. Multiple treatment options are practiced, but the available small molecule drugs suffer from dose-limiting toxicity and undesirable side effects. The need for new, less toxic treatments is a pressing concern. Here, we demonstrate that (-)-agelastatin A (1a), a pyrrole-imidazole alkaloid obtained from a marine sponge, exhibits potent in vitro activity against primary cell lines of CLL and disclose the synthesis of several analogues that are equipotent or exceed the potency of the natural product. The novel synthetic analogue, 13-debromo-13-trifluoromethyl agelastatin A (1j), showed higher activity than the natural product when tested against the same cell lines and is the most potent agelastatin derivative reported to date. A detailed in vitro structure-activity relationship of 1a in CLL compared to that of 22 synthetic analogues is described along with preliminary in vivo pharmacokinetic and metabolism studies on the most potent compounds.