(6-Naphthalen-1-ylpyrrolo[2,1-d][1,5]benzothiazepin-7-yl) pyridine-4-carboxylate

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并硫氮卓类
• 英文名称: (6-Naphthalen-1-ylpyrrolo[2,1-d][1,5]benzothiazepin-7-yl) pyridine-4-carboxylate
• 化学式: C₂₈H₁₈N₂O₂S
• 分子量: 446.529
• InChiKey: CXXXYGZWAQWPAQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.9
• 重原子数：
  33
• 可旋转键数：
  4
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  69.4
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  Alpha-溴代-1-萘乙酸乙酯 在 sodium hydroxide 、 五氯化磷 、 potassium hydride 、 sodium hydride 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 为溶剂， 反应 29.0h， 生成 (6-Naphthalen-1-ylpyrrolo[2,1-d][1,5]benzothiazepin-7-yl) pyridine-4-carboxylate
  参考文献：
  名称：

  Pyrrolo[1,5]benzoxa(thia)zepines as a New Class of Potent Apoptotic Agents. Biological Studies and Identification of an Intracellular Location of Their Drug Target

  摘要：

  We have recently developed five novel pyrrolo-1,5-benzoxazepines as proapoptotic agents. Their JNK-dependent induction of apoptosis in tumor cells suggested their potential as novel anticancer agents. The core structure of the apoptotic agent 6 was investigated, and the SARs were expanded with the design and synthesis of several analogues. To define the apoptotic mechanism of the new compounds and the localization of their drug target, two analogues of 6 were designed and synthesized to delineate events leading to JNK activation. The cell-penetrating compound 16 induced apoptosis in tumor cells, while its nonpenetrating analogue, 17, was incapable of inducing apoptosis or activating JNK. Plasma membrane permeabilization of tumor cells resulted in 17-induced JNK activation, suggesting that the pyrrolo-1,5-benzoxazepine molecular target is intracellular. Interestingly, compound 6 displayed cytotoxic activity against a panel of human tumor cell lines but demonstrated negligible toxicity in vivo with no effect on the animals' hematology parameters.

  DOI：

  10.1021/jm049402y

文献信息

• [EN] MICROTUBULE TARGETING AGENTS<br/>[FR] AGENTS DE CIBLAGE DE MICROTUBULES
  申请人：TRINITY COLLEGE DUBLIN

  公开号：WO2007088528A1

  公开（公告）日：2007-08-09

  [EN] The present invention provides for the use of a compound having the general formula (I), wherein: (i) A represents O or S; (ii) the cyclic group labelled F represents a benzyl group, a 2,3-naphthyl group or a benzyl group substituted with ethoxycarbonyl at the 2-position; (iii) and Y represents N(CH₃)₂, NHCH₃, CH₃ or pyridine; as an agent for one or more of the group consisting of an attenuating microtubule growth, depolymerising microtubules, arresting G2/M transition, activation of CDK1 activity, treatment of coronary heart disease, treatment of restenosis, treatment of arteriosclerosis and treatment of malaria.
  [FR] L'invention concerne l'utilisation d'un composé représenté par la formule générale (I), dans laquelle: (i) A représente O ou S; (ii) le groupe cyclique désigné F représente un groupe benzyle, un groupe 2,3-naphtyle ou un groupe benzyle substitué par éthoxycarbonyle en position 2; (iii) Y représente N(CH₃)₂, NHCH_3,CH₃ ou pyridine; en tant qu'agent d'un ou plusieurs du groupe consistant en l'atténuation de la croissance de microtubules, la dépolymérisation de microtubules, l'arrêt de la transition de G2/M, l'activation de CDK1, le traitement de la maladie cardiaque coronarienne, le traitement de la resténose, le traitement de l'athérosclérose et le traitement de la malaria.