bis(2-methoxyethyl) 4-(2-chlorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate | 165390-06-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: bis(2-methoxyethyl) 4-(2-chlorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate
• 英文别名: dimethyl bis(2-methoxyethyl) 4-(2-chlorophenyl)-1,4-dihydro-2,6-dimethylpyridine-3,5-dicarboxylate
• CAS: 165390-06-7
• 化学式: C₂₁H₂₆ClNO₆
• 分子量: 423.894
• InChiKey: WYRBORTXHPNNHT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  29
• 可旋转键数：
  11
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  83.1
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  乙酰乙酸甲氧乙酯 、 2-氯苯甲醛 在 氨 作用下， 以 乙醇 、 水 为溶剂， 反应 3.0h， 以49%的产率得到bis(2-methoxyethyl) 4-(2-chlorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate
  参考文献：
  名称：

  WO2008/6070

  摘要：

  公开号：

文献信息

• Synthesis, Evaluation of Pharmacological Activity, and Molecular Docking of 1,4-Dihydropyridines as Calcium Antagonists
  作者：Moataz Ahmed Shaldam、Mervat Hamed El-Hamamsy、Dalia Osama Saleh、Tarek Fathy El-Moselhy

  DOI：10.1248/cpb.c15-00737

  日期：——

  approximately three-fold more active than nifedipine as a calcium antagonist. A docking study with the DHP receptor model was performed to interpret the differences in calcium antagonist activities. The molecular docking study demonstrated that the lipophilicity of the substituted phenyl group at the 4-position of the DHP ring is an important factor that could increase the activity of the calcium antagonist

  1,4-二氢吡啶（DHP）是一类重要的钙拮抗剂。它通过L型电压依赖性钙通道抑制细胞外Ca + 2的流入。合成了两个系列的硝苯地平类似物并评估为钙拮抗剂。硝苯地平的邻硝基苯基环被邻或间氯苯基取代基取代。IC50值表明，某些化合物的活性类似于硝苯地平或比硝苯地平更具活性。在DHP环的3和5位上用适当体积的基团（如乙酯）取代，得到3h，其活性比硝苯地平作为钙拮抗剂高3倍。进行了与DHP受体模型的对接研究，以解释钙拮抗剂活性的差异。分子对接研究表明，DHP环4位上的取代苯基的亲脂性是一个重要因素，考虑到空间因素，它可以增加钙拮抗剂的活性。庞大的基团干扰了与Tyr1460的环到环疏水相互作用，并限制了增加DHP环3和5位上的酯烃链长度的效率，以此作为提高活性的一种方法。DHP环的4位上苯环上存在螯合取代基可确保与受体的牢固结合，从而确保闭通道构象的稳定。
• 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。
• [EN] COMPOUNDS AND COMBINATIONS THEREOF FOR INHIBITING BETA-AMYLOID PRODUCTION AND METHODS OF USE THEREOF<br/>[FR] COMPOSÉS ET COMBINAISONS DE CEUX-CI POUR INHIBER LA PRODUCTION DE BÊTA-AMYLOÏDE ET PROCÉDÉS D'UTILISATION DE CES COMPOSÉS ET COMBINAISONS
  申请人：ROSKAMP RES LLC

  公开号：WO2008006070A2

  公开（公告）日：2008-01-10

  [EN] 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 ß-amyloid production, ß-amyloid deposition, ß-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 ß-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.
  [FR] L'invention concerne des composés qui peuvent être utilisés en combinaison pour traiter des maladies associées à un état lié à une accumulation cérébrale de l'amyloïde d'Alzheimer, telles que la maladie d'Alzheimer. L'invention concerne également des procédés de traitement ou de réduction du risque de développement de la production de ß-amyloïde, du dépôt de ß-amyloïde, de la neurotoxicité par le ß-amyloïde (comprenant l'hyperphosphorylation anormale de tau) et de la microgliose associée à l'accumulation cérébrale de l'amyloïde d'Alzheimer, par l'administration de quantités thérapeutiquement efficaces de composés qui, en combinaison, peuvent diminuer la production du ß-amyloïde et l'entrée capacitative de calcium dans les cellules. L'invention concerne en outre des procédés de diagnostic des maladies associées à l'accumulation cérébrale de l'amyloïde d'Alzheimer chez l'animal ou l'humain par l'administration de quantités des composés efficaces du point de vue du diagnostic.