2-amino-4,5,6,7-tetrahydrobenzothiazole hydroiodide | 118926-63-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 2-amino-4,5,6,7-tetrahydrobenzothiazole hydroiodide
• 英文别名: 4,5,6,7-tetrahydro-benzothiazol-2-ylamine; hydriodide；4,5,6,7-Tetrahydro-1,3-benzothiazol-3-ium-2-amine;iodide；4,5,6,7-tetrahydro-1,3-benzothiazol-3-ium-2-amine;iodide
• CAS: 118926-63-9
• 化学式: C₇H₁₀N₂S*HI
• 分子量: 282.148
• InChiKey: SRIBOJGMWSVQMR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.22
• 重原子数：
  11
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  67.2
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-amino-4,5,6,7-tetrahydrobenzothiazole hydroiodide 在 sodium carbonate 作用下， 以 水 为溶剂， 以3.39 g的产率得到4,5,6,7-四氢苯并噻唑-2-胺
  参考文献：
  名称：

  Identification of new aminoacid amides containing the imidazo[2,1-b]benzothiazol-2-ylphenyl moiety as inhibitors of tumorigenesis by oncogenic Met signaling

  摘要：

  The Met receptor tyrosine kinase is a promising target in anticancer therapies for its role during tumor evolution and resistance to treatment. It is characterized by an unusual structural plasticity as its active site accepts different inhibitor binding modes. Such feature can be exploited to identify distinct agents targeting tumor dependence and/or resistance by oncogenic Met. Here we report the identification of bioactive agents, featuring a new 4-(imidazo[2,1-b]benzothiazol-2-yl)phenyl moiety, targeting cancer cells dependent on oncogenic Met. One of these compounds (7c; Triflorcas) impairs survival, anchorage-independent growth, and in vivo tumorigenesis, without showing side effects. Our medicinal chemistry strategy was based on an in-house Met-focused library of aminoacid-amide derivatives enriched through structure-based computer modeling, taking into account the Met multiple-binding-mode feature. Altogether, our findings show how a rational structure-based drug design approach coupled to cell-based drug evaluation strategies can be applied in medicinal chemistry to identify new agents targeting a given oncogenic-dependency setting. (C) 2011 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2011.10.051
• 作为产物：
  描述：

  环己酮 、 硫脲 在 碘 作用下， 反应 12.0h， 以57%的产率得到2-amino-4,5,6,7-tetrahydrobenzothiazole hydroiodide
  参考文献：
  名称：

  具有神经保护作用的新型p53灭活剂：2-亚氨基-2,3,4,5,6,7-六氢苯并噻唑和2-亚氨基-2,3,4,5,6,7-六氢苯并恶唑衍生物的合成和药理评估。

  摘要：

  肿瘤抑制蛋白p53是一种细胞内蛋白，在生化级联反应中至关重要，可通过凋亡导致细胞死亡。最近的研究确定了四氢苯并噻唑类似物pifithrin-alpha（2）作为p53抑制剂，可有效保护神经元细胞免受各种致命伤害并减少抗癌药物的副作用。由于p53的上调已被描述为包括阿尔茨海默氏病在内的几种神经退行性疾病的共同特征，因此合成了2种和新型类似物（3-16）以（i）评估四氢苯并噻唑类似物作为神经保护剂的价值，以及（ii）定义p53失活的结构要求。不仅2在组织培养和体内中风模型中均表现出神经保护活性，而且化合物6、7、10、13、15

  DOI：

  10.1021/jm020044d

文献信息

• Novel p53 Inactivators with Neuroprotective Action:  Syntheses and Pharmacological Evaluation of 2-Imino-2,3,4,5,6,7-hexahydrobenzothiazole and 2-Imino-2,3,4,5,6,7-hexahydrobenzoxazole Derivatives
  作者：Xiaoxiang Zhu、Qian-sheng Yu、Roy G. Cutler、Carsten W. Culmsee、Harold W. Holloway、Debomoy K. Lahiri、Mark P. Mattson、Nigel H. Greig

  DOI：10.1021/jm020044d

  日期：2002.11.1

  feature of several neurodegenerative disorders, including Alzheimer's disease, 2 and novel analogues (3-16) were synthesized to (i) assess the value of tetrahydrobenzothiazole analogues as neuroprotective agents and (ii) define the structural requirements for p53 inactivation. Not only did 2 exhibit neuroprotective activity in both tissue culture and in vivo stroke models but also compounds 6, 7, 10, 13

  肿瘤抑制蛋白p53是一种细胞内蛋白，在生化级联反应中至关重要，可通过凋亡导致细胞死亡。最近的研究确定了四氢苯并噻唑类似物pifithrin-alpha（2）作为p53抑制剂，可有效保护神经元细胞免受各种致命伤害并减少抗癌药物的副作用。由于p53的上调已被描述为包括阿尔茨海默氏病在内的几种神经退行性疾病的共同特征，因此合成了2种和新型类似物（3-16）以（i）评估四氢苯并噻唑类似物作为神经保护剂的价值，以及（ii）定义p53失活的结构要求。不仅2在组织培养和体内中风模型中均表现出神经保护活性，而且化合物6、7、10、13、15
• Tetrahydrobenzothiazole analogues as neuroprotective agents
  申请人：——

  公开号：US20040067991A1

  公开（公告）日：2004-04-08

  This invention relates generally to tetrahydrobenzothiazole analogues and tetrahydrobenzooxyzole analogues, to pharmaceutical compositions which include these compounds and a pharmaceutically acceptable carrier, and to methods of treatment using these compounds. The invention also encompasses pharmaceutically acceptable esters, amides, and salts of such compounds. The invention further provides a method of reducing or delaying apoptosis in a population of cells, comprising contacting the population of cells with a tetrahydrobenzothiazole analogue or a tetrahydrobenzooxyzole analogue, thereby reducing or delaying apoptosis in the population of cells.

  本发明涉及四氢苯并噻唑类似物和四氢苯并噁唑类似物，包括这些化合物和药物可接受载体的制药组合物，以及使用这些化合物的治疗方法。本发明还包括这些化合物的药物可接受酯，酰胺和盐。本发明还提供一种减少或延迟细胞群中凋亡的方法，包括将四氢苯并噻唑类似物或四氢苯并噁唑类似物与细胞群接触，从而减少或延迟细胞群中的凋亡。
• TETRAHYDROBENZOTHIAZOLE ANALOGUES AS NEUROPROTECTIVE AGENTS
  申请人：Greig Nigel H

  公开号：US20080319032A1

  公开（公告）日：2008-12-25

  This invention relates generally to tetrahydrobenzothiazole analogues and tetrahydrobenzooxyzole analogues, to pharmaceutical compositions which include these compounds and a pharmaceutically acceptable carrier, and to methods of treatment using these compounds. The invention also encompasses pharmaceutically acceptable esters, amides, and salts of such compounds. The invention further provides a method of reducing or delaying apoptosis in a population of cells, comprising contacting the population of cells with a tetrahydrobenzothiazole analogue or a tetrahydrobenzooxyzole analogue, thereby reducing or delaying apoptosis in the population of cells.

  本发明涉及四氢苯并噻唑类似物和四氢苯并噁唑类似物，以及包括这些化合物和药用可接受载体的制药组合物和使用这些化合物的治疗方法。本发明还包括这些化合物的药用可接受酯、酰胺和盐。本发明还提供一种减少或延迟细胞群体凋亡的方法，包括将细胞群体与四氢苯并噻唑类似物或四氢苯并噁唑类似物接触，从而减少或延迟细胞群体的凋亡。
• Imino-tetrahydro-benzothiazole Derivatives as p53 Inhibitors:  Discovery of a Highly Potent in Vivo Inhibitor and Its Action Mechanism
  作者：Nicolas Pietrancosta、Anice Moumen、Rosanna Dono、Paul Lingor、Veronique Planchamp、Fabienne Lamballe、Mathias Bähr、Jean-Louis Kraus、Flavio Maina

  DOI：10.1021/jm060318n

  日期：2006.6.1

  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.
• 2-Aminothiazoles: A new class of agonist allosteric enhancers of A1 adenosine receptors
  作者：Mahendra D. Chordia、Lauren J. Murphree、Timothy L. Macdonald、Joel Linden、Ray A. Olsson

  DOI：10.1016/s0960-894x(02)00236-6

  日期：2002.6

  This report describes the synthesis and structure-activity relationships of a new class of A(1) adenosine receptor agonist allosteric enhancers, 2-aminothiazolium salts. The EC50 of compounds 6a, 6b, 7, and 8 were 0.3, 4.5, 3.8, and 1.2 muM, substantially lower than that of the 'Gold Standard' 2-amino-3-benzoyl thiophene (PD 81,723), which has an EC50 of 38 muM. (C) 2002 Elsevier Science Ltd. All rights reserved.