2-amino-4,4a,5,6,7,8,8a,9-octahydro-naphtho[2,3-d]thiazole | 850733-08-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 萘并噻唑类
• 英文名称: 2-amino-4,4a,5,6,7,8,8a,9-octahydro-naphtho[2,3-d]thiazole
• 英文别名: 4,4a,5,6,7,8,8a,9-octahydrobenzo[f][1,3]benzothiazol-2-amine
• CAS: 850733-08-3
• 化学式: C₁₁H₁₆N₂S
• 分子量: 208.327
• InChiKey: JHUMDYXYRRVVRQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  14
• 可旋转键数：
  0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.73
• 拓扑面积：
  67.2
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-amino-4,4a,5,6,7,8,8a,9-octahydro-naphtho[2,3-d]thiazole 在 biological medium 作用下， 以 甲苯 为溶剂， 反应 54.0h， 生成 2-(4-Nitro-phenyl)-4,4a,5,6,7,8,8a,9-octahydro-10-thia-1,3a-diaza-pentaleno[1,2-b]naphthalene
  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
• 作为产物：
  描述：

  2-萘烷酮 、 硫脲 在 碘 作用下， 反应 12.0h， 以47%的产率得到2-amino-4,4a,5,6,7,8,8a,9-octahydro-naphtho[2,3-d]thiazole
  参考文献：
  名称：

  Novel cyclized Pifithrin-α p53 inactivators: synthesis and biological studies

  摘要：

  Starting from various cyclic or bicyclic ketones, we have synthesized novel Pifithrin-a analogues bearing different methyl substituted phenyl ketone groups at the N-3-position of the 2-iminothiazole heterocycle. From stability studies in a biological medium as well as under specific chemical conditions, we have shown by NMR techniques that through a dehydration process, some derivatives can generate their corresponding cyclized analogues. All of the new analogues, Pifithrin-like and polycyclic dehydrated derivatives were assessed for their p53 inactivation potency by measuring survival of cortical neurons, whose death was induced by the DNA-damaging agent etoposide. Pifithrin-alpha like 2f as well as the cyclic dehydrated 6b analogue were found to be one log more potent p53 inactivators than reference compound Pft-alpha, with EC50 values ranging around 30 nM. These results support the finding that p53 inactivation by Pft-alpha analogues could be also due to the presence of the cyclic dehydrated Pft-alpha forms, generated in situ in the biological assay incubation medium. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2005.01.075