2-[[2-(乙酰氧基甲氧基)-2-氧代乙基]-[2-[2-[2-(二(羧甲基)氨基)苯氧基]乙氧基]苯基]氨基]乙酸 | 139890-68-9

• 物质功能分类: 生物化工 - 生化试剂 - 激动剂抑制剂
• 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
• 中文名称: 2-[[2-(乙酰氧基甲氧基)-2-氧代乙基]-[2-[2-[2-(二(羧甲基)氨基)苯氧基]乙氧基]苯基]氨基]乙酸
• 英文名称: 1,2-Bis(2-aminophenoxy)ethane N,N,N',N'-tetraacetic acid acetoxymethyl ester
• 英文别名: 2-[2-[2-[2-[[2-(acetyloxymethoxy)-2-oxoethyl]-(carboxymethyl)amino]phenoxy]ethoxy]-N-(carboxymethyl)anilino]acetic acid
• CAS: 139890-68-9
• 化学式: C₂₅H₂₈N₂O₁₂
• 分子量: 548.5
• InChiKey: ZYOUCRHWAYJCPN-UHFFFAOYSA-N

物化性质

• 熔点：
  84-96°C
• 沸点：
  775.0±60.0 °C(Predicted)
• 密度：
  1.440±0.06 g/cm3(Predicted)
• 溶解度：
  氯仿（微溶）、DMSO（微溶）、乙酸乙酯（微溶）

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  39
• 可旋转键数：
  19
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  189
• 氢给体数：
  3
• 氢受体数：
  14

安全信息

• 危险品标志：
  Xi

制备方法与用途

细胞透性螯合剂：BAPTA-AM

BAPTA-AM 是一种细胞透性螯合剂，对 Ca2+ 的选择性超过 Mg2+，能够有效控制胞内 Ca2+ 水平。与 EDTA 和 EGTA 相比，BAPTA 对 Ca2+ 的选择性更强，并且金属螯合作用在 pH 值变化时更为稳定。

生物活性

体外研究显示：

• BAPTA/AM 作为一种已知可渗透的钙螯合剂，能够防止自由基介导的毒性作用，促进非神经元细胞凋亡，并通过保护神经元免受缺血性损伤产生有益效果。
• 还有人提出，BAPTA/AM 可能诱导 I-IL-60 肿瘤细胞中晚期但不是早期的钙内流增加。
• 混合皮层细胞培养物（DIV 13-16）暴露于 10 μM BAPTA/AM 24 或 48 小时后，神经元损伤程度为 45-70%，可通过在 24-48 小时后的乳酸脱氢酶（LDH）释放量增加来评估。
• 在 3-10 μM BAPTA/AM 暴露下，皮质培养物在 48 小时时表现出剂量依赖性神经元损伤。

用途

**BAPTA 是一种钙选择性螯合剂，对 Ca2+ 的亲和力是 Mg2+ 的 100 倍以上。其基本的螯合单位与 EDTA 相似，只是两个脂肪氮被芳香氮替代。因此，在生理 pH 下 BAPTA 不会被质子化。BAPTA 的 pKa3 为 5.47，pKa4 为 6.36，这表明去质子化步骤并不包括 Ca2+ 螯合过程。由于不受质子的干扰，它的螯合作用比 EGTA 更强。

BAPTA-AM 是 BAPTA 的乙酰甲酯衍生物，通过 AM 法能够轻易地负载到细胞中，使其成为监控细胞内钙离子的理想工具。

文献信息

• Compounds for inhibiting beta-amyloid production and methods of identifying the compounds
  申请人：Mullan J. Michael

  公开号：US20060188938A1

  公开（公告）日：2006-08-24

  Provided are compounds useful for treating diseases associated with a cerebral accumulation of Alzheimer's amyloid, such as Alzheimer's disease. Also provided are methods for screening for such compounds, by measuring capacitative calcium entry in cells which optionally overexpress APP or a fragment thereof. Also provided are methods of treating or reducing the risk of developing β-amyloid production, β-amyloid deposition, β-amyloid neurotoxicity (including abnormal hyperphosphorylation of tau) and microgliosis associated with cerebral accumulation of Alzheimer's amyloid by administering therapeutically effective amounts of compounds which decrease β-amyloid production and capacitative calcium entry in cells. Further provided are methods for diagnosing diseases associated with cerebral accumulation of Alzheimer's amyloid in animals or humans by administering diagnostically effective amounts of compounds which inhibit capacitative calcium entry in cells.

  提供了对治疗与阿尔茨海默病相关的脑部淀粉样蛋白沉积疾病（如阿尔茨海默病）有用的化合物。还提供了筛选此类化合物的方法，通过测量细胞中的电容性钙离子入流，该细胞可选择过表达APP或其片段。还提供了通过给予治疗有效量的化合物来治疗或降低β-淀粉样蛋白产生、β-淀粉样蛋白沉积、β-淀粉样蛋白神经毒性（包括tau异常的超磷酸化）和与阿尔茨海默病相关的微胶质细胞病的风险的方法，这些化合物降低细胞中的β-淀粉样蛋白产生和电容性钙离子入流。此外，还提供了通过给予诊断有效量的化合物来诊断动物或人类中与阿尔茨海默病相关的脑部淀粉样蛋白沉积疾病的方法，这些化合物抑制细胞中的电容性钙离子入流。
• Compounds and Combinations Thereof for Inhibiting Beta-Amyloid Production and Methods of Use Thereof
  申请人：Paris Daniel

  公开号：US20080058330A1

  公开（公告）日：2008-03-06

  Provided are compounds which can be used in combination for treating diseases associated with a condition associated with cerebral accumulation of Alzheimer's amyloid, such as Alzheimer's disease. Also provided are methods of treating or reducing the risk of developing β-amyloid production, β-amyloid deposition, β-amyloid neurotoxicity (including abnormal hyperphosphorylation of tau) and microgliosis associated with cerebral accumulation of Alzheimer's amyloid by administering therapeutically effective amounts of compounds which in combination can decrease β-amyloid production and capacitative calcium entry in cells. Further provided are methods for diagnosing diseases associated with cerebral accumulation of Alzheimer's amyloid in animals or humans by administering diagnostically effective amounts of the compounds.

  提供了一些化合物，可以组合使用来治疗与阿尔茨海默病淀粉样蛋白相关的疾病，如阿尔茨海默病。还提供了一种方法，通过给予治疗有效量的化合物组合来减少β-淀粉样蛋白的产生和细胞中的电容性钙离子进入，从而治疗或降低发生β-淀粉样蛋白产生、β-淀粉样蛋白沉积、β-淀粉样蛋白神经毒性（包括tau异常过度磷酸化）和与阿尔茨海默病淀粉样蛋白相关的微胶质病变。此外，还提供了一种方法，通过给予诊断有效量的化合物来诊断动物或人类中与阿尔茨海默病淀粉样蛋白相关的疾病。
• Compounds for Inhibiting Beta-Amyloid Production and Methods of Identifying the Compounds
  申请人：Mullan Michael J.

  公开号：US20100215735A1

  公开（公告）日：2010-08-26

  Provided are compounds useful for treating diseases associated with a cerebral accumulation of Alzheimer's amyloid, such as Alzheimer's disease. Also provided are methods for screening for such compounds, by measuring capacitative calcium entry in cells which optionally overexpress APP or a fragment thereof. Also provided are methods of treating or reducing the risk of developing β-amyloid production, β-amyloid deposition, β-amyloid neurotoxicity (including abnormal hyperphosphorylation of tau) and microgliosis associated with cerebral accumulation of Alzheimer's amyloid by administering therapeutically effective amounts of compounds which decrease β-amyloid production and capacitative calcium entry in cells. Further provided are methods for diagnosing diseases associated with cerebral accumulation of Alzheimer's amyloid in animals or humans by administering diagnostically effective amounts of compounds which inhibit capacitative calcium entry in cells.

  提供了一些化合物，可用于治疗与阿尔茨海默氏淀粉样物质在大脑中积累有关的疾病，如阿尔茨海默病。还提供了筛选这些化合物的方法，通过测量在细胞中的电容性钙离子进入，这些细胞可以选择性地过表达APP或其片段。还提供了通过给予治疗有效量的化合物来治疗或降低发生β-淀粉样物质产生、β-淀粉样物质沉积、β-淀粉样物质神经毒性（包括tau异常过磷酸化）和与阿尔茨海默氏淀粉样物质在大脑中积累有关的小胶质细胞增生的风险的方法，这些化合物可以减少β-淀粉样物质产生和细胞中的电容性钙离子进入。此外，还提供了通过给动物或人体内给予诊断有效量的化合物来诊断与阿尔茨海默氏淀粉样物质在大脑中积累有关的疾病的方法，这些化合物可以抑制细胞中的电容性钙离子进入。
• Conductance of improperly folded proteins through the secretory pathway and related methods for treating disease
  申请人：——

  公开号：US20020132770A1

  公开（公告）日：2002-09-19

  This invention provides the methodology and agents for treating any disease or clinical condition which is at least partly the result of endoplasmic reticulum-associated retention of proteins. Thus, the methods and agents of the present invention provide for the release of normally retained proteins from the endoplasmic reticulum. The present invention is particularly useful for treating any disease or clinical condition which is at least partly the result of endoplasmic reticulum-associated retention or degradation of mis-assembled or mis-folded proteins.

  本发明提供了治疗任何疾病或临床症状的方法和制剂，这些疾病或临床症状至少部分是内质网相关蛋白质滞留的结果。因此，本发明的方法和制剂可将正常滞留的蛋白质从内质网中释放出来。本发明尤其适用于治疗至少部分是内质网相关性滞留或降解错误组装或错误折叠蛋白质所致的任何疾病或临床症状。
• Lipophilic diesters of chelating agent for inhibition of enzyme activity
  申请人：Striem Sarina

  公开号：US20060167092A1

  公开（公告）日：2006-07-27

  The present invention relates to the use of lipophilic diesters of the chelating agent 1,2-bis(2 aminophenoxy)ethane-N,N,N′,N′-tetraacetic acid (BAPTA) for inhibition of proteolytic activities of certain metalloproteinases and of calpain. The invention further relates to methods for preventing, treating or managing MMP-related and calpain-related diseases or disorders in mammals comprising administering to a mammal in need thereof, a pharmaceutical composition comprising a therapeutically effective amount of said lipophilic diesters of the chelating agent BAPTA.

  本发明涉及螯合剂1,2-双(2-氨基苯氧基)乙烷-N,N,N′,N′-四乙酸(BAPTA)亲脂二酯用于抑制某些金属蛋白酶和钙蛋白酶的蛋白水解活性的用途。本发明进一步涉及预防、治疗或控制哺乳动物中与金属蛋白酶相关和钙蛋白酶相关的疾病或失调的方法，包括向有需要的哺乳动物施用药物组合物，该药物组合物包含治疗有效量的所述螯合剂 BAPTA 的亲脂二酯。