环丙硫蛋白-α-对硝基 | 60477-38-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 中文名称: 环丙硫蛋白-α-对硝基
• 英文名称: 2-(4-nitrophenyl)-5,6,7,8-tetrahydrobenzo[d]imidazo[2,1-b]thiazole
• 英文别名: 2-(4-nitrophenyl)-5,6,7,8-tetrahydroimidazo[2,1-b]benzothiazole；5,6,7,8-tetrahydro-2-(4-nitrophenyl)imidazo[2,1-b]benzothiazole；2-(4-nitro-phenyl)-5,6,7,8-tetrahydro-benz[d]imidazo[2,1-b]thiazole；2-(4-Nitro-phenyl)-5,6,7,8-tetrahydro-benz[d]imidazo[2,1-b]thiazol；2-(4-Nitrophenyl)-5,6,7,8-tetrahydroimidazo[2,1-b][1,3]benzothiazole
• CAS: 60477-38-5
• 化学式: C₁₅H₁₃N₃O₂S
• 分子量: 299.353
• InChiKey: XMFNSEDROOHGBY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  21
• 可旋转键数：
  1
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  91.4
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  环丙硫蛋白-α-对硝基 在 盐酸 、 硫酸 、 铁粉 作用下， 以 甲醇 、 水 为溶剂， 反应 1.0h， 生成 4-(5,6,7,8-tetrahydroimidazo[2,1-b]benzothiazol-2-yl)benzenamine hydrochloride
  参考文献：
  名称：

  Synthesis and biological evaluation of imidazolo[2,1-b]benzothiazole derivatives, as potential p53 inhibitors

  摘要：

  Since activation of p53 in response to cytotoxic stress may have proapoptotic or protective effects depending on the nature of the injury, inhibitors of p53 may have therapeutic interest as modulators of chemotherapy toxicity or efficacy. In an attempt to identify novel p53 inhibitors, a quality collection of compounds structurally related to pifithrin-beta were designed and synthesized as potential inhibitors of p53. The biochemical and biological evaluations supported that compounds of the tetrahydrobenzothiazole series were inhibitors of the p53 transcriptional activity and were effective in enhancing paclitaxel-induced apoptosis. In contrast, in spite of the increased cytotoxic potency, selected compounds of the benzothiazole series were not able to modulate the transcriptional activity of p53, as indicated by lack of change of p21 expression. The therapeutic interest of the compounds of the former series in combination with taxanes was confirmed in a human tumor xenograft model. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.01.039
• 作为产物：
  描述：

  4,5,6,7-四氢苯并噻唑-2-胺 在 biological medium 作用下， 以 甲苯 为溶剂， 反应 54.0h， 生成 环丙硫蛋白-α-对硝基
  参考文献：
  名称：

  Imino-tetrahydro-benzothiazole Derivatives as p53 Inhibitors:  Discovery of a Highly Potent in Vivo Inhibitor and Its Action Mechanism

  摘要：

  Several neurological disorders manifest symptoms that result from the degeneration and death of specific neurons. p53 is an important modulator of cell death, and its inhibition could be a therapeutic approach to several neuropathologies. Here, we report the design, synthesis, and biological evaluation of novel p53 inhibitors based on the imino-tetrahydrobenzothiazole scaffold. By performing studies on their mechanism of action, we find that cyclic analogue 4b and its open precursor 2b are more potent than pifithrin-alpha (PFT-R), which is known to block p53 pro-apoptotic activity in vitro and in vivo without acting on other proapoptotic pathways. Using spectroscopic methods, we also demonstrate that open form 2b is more stable than 4b in biological media. Compound 2b is converted into its corresponding active cyclic form through an intramolecular dehydration process and was found two log values more active in vivo than PFT-alpha. Thus, 2b can be considered as a new prodrug prototype that prevents in vivo p53-triggered cell death in several neuropathologies and possibly reduces cancer therapy side effects.

  DOI：

  10.1021/jm060318n

文献信息

• Imidazothiazole compound
  申请人：Nikken Chemicals Co., Ltd.

  公开号：US05919799A1

  公开（公告）日：1999-07-06

  An imidazothiazole compound having the formula (A): ##STR1## wherein R.sub.1 is a phenyl or napthyl which may have a substituent, R.sub.2 is an acyl, and the two bonds at dotted line portions may or may not exist simultaneously, or a pharmacologically acceptable salt thereof and an agent for overcoming resistance to an anti-neoplastic agent or an enhancer for the effect of an anti-neoplastic agent comprising said compound or a pharmacologically acceptable salt thereof as an active ingredient.

  一种具有以下结构式（A）的咪唑噻唑化合物：其中R.sub.1是苯或萘基，可能带有取代基；R.sub.2是酰基；虚线部分的两个键可以同时存在也可以不存在；或者其药理学上可接受的盐，以及克服抗肿瘤药物的耐药性或增强抗肿瘤药物效果的药剂，包括所述化合物或其药理学上可接受的盐作为活性成分。
• IMIDAZOTHIAZOLE COMPOUNDS
  申请人：Nikken Chemicals Company, Limited

  公开号：EP0816366A1

  公开（公告）日：1998-01-07

  An imidazothiazole compound having the formula (A): wherein R1 is a phenyl or napthyl which may have a substituent, R2 is an acyl, and the two bonds at dotted line portions may or may not exist simultaneously, or a pharmacologically acceptable salt thereof and an agent for overcoming resistance to an anti-neoplastic agent or an enhancer for the effect of an anti-neoplastic agent comprising said compound or a pharmacologically acceptable salt thereof as an active ingredient.

  一种咪唑噻唑化合物，其式为(A)： 其中 R1 是苯基或萘基，可以有取代基，R2 是酰基，虚线部分的两个键可以同时存在，也可以不存在，或其药理上可接受的盐，以及一种用于克服抗肿瘤药物抗药性的制剂或一种抗肿瘤药物效果增强剂，其活性成分包括上述化合物或其药理上可接受的盐。
• Use of P53 inhibitors for the treatment of side effects of cancer therapy
  申请人：BOARD OF TRUSTEES OF THE UNIVERSITY OF ILLINOIS

  公开号：EP1797880A2

  公开（公告）日：2007-06-20

  The therapeutic use of temporary p53 inhibitors in the treatment of p53-mediated diseases, conditions, and injuries is disclosed.

  本研究公开了临时 p53 抑制剂在治疗 p53 介导的疾病、病症和损伤中的治疗用途。
• p53 Inhibitors and therapeutic use of the same
  申请人：The Board of Trustees of the University of Illinois

  公开号：US20020019425A1

  公开（公告）日：2002-02-14

  The therapeutic use of temporary p53 inhibitors in the treatment of p53-mediated diseases, conditions, and injuries is disclosed.

  本研究公开了临时 p53 抑制剂在治疗 p53 介导的疾病、病症和损伤中的治疗用途。
• p53 inhibitors and therapeutic use of the same
  申请人：The Board of Trustees of the University of Illinois

  公开号：US20020006941A1

  公开（公告）日：2002-01-17

  The therapeutic use of temporary p53 inhibitors in the treatment of p53-mediated diseases, conditions, and injuries is disclosed.

  本研究公开了临时 p53 抑制剂在治疗 p53 介导的疾病、病症和损伤中的治疗用途。