非洛地平杂质C | 79925-38-5

• 物质功能分类: 分析化学 - 标准品 - 药典标准品和杂质标准品
• 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
• 中文名称: 非洛地平杂质C
• 中文别名: 4-(2,3-二氯苯基)-2,6-二甲基-1,4-二氢吡啶-3,5-二羧酸二乙酯；非洛地平杂质C(EP)标准品；二乙基4-(2,3-二氯苯基)-2,6-二甲基-1,4-二氢吡啶-3,5-二羧酸；非洛地平EP杂质C
• 英文名称: 4-(2,3-dichloro-phenyl)-2,6-dimethyl-1,4-dihydro-pyridine-3,5-dicarboxylic acid diethyl ester
• 英文别名: 4-(2,3-dichlorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylic acid diethyl ester；4-(2,3-dichlorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylicacid diethyl ester；diethyl 4-(2,3-dichlorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate；2,6-dimethyl-3,5-dicarboethoxy-4-(2,3-dichlorophenyl)-1,4-dihydropyridine；nemadipine B；diethyl 4-(2,3-dichlorophenyl)-1,4-dihydro-2,6-dimethylpyridine-3,5-dicarboxylate
• CAS: 79925-38-5
• 化学式: C₁₉H₂₁Cl₂NO₄
• 分子量: 398.286
• InChiKey: BLLWOXSSRQPDAT-UHFFFAOYSA-N

物化性质

• 熔点：
  122-124°C
• 沸点：
  483.3±45.0 °C(Predicted)
• 密度：
  1?+-.0.06 g/cm3(Predicted)
• 溶解度：
  可溶于氯仿（少许）、DMSO（少许）、甲醇（少许）

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  26
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.37
• 拓扑面积：
  64.6
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  非洛地平杂质C 在 吡啶 、 pyridinium hydrobromide perbromide 、 potassium carbonate 作用下， 以 四氢呋喃 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 14.67h， 生成
  参考文献：
  名称：

  1,4-Dihydropyridines bearing a pharmacophoric fragment of lidoflazine

  摘要：

  A series of 1,4-dihydropyridines bearing a pharmacophoric fragment of Iidoflazine was synthesized. The compounds were evaluated for inotropic, chronotropic, and calcium antagonist activities. All compounds behave as inotropic and chronotropic agents, except for compounds 4b, 5a, and 5b, which exibit a rather weak calcium antagonism in vascular smooth muscle (like aorta). Compound 5b is about twofold more potent in decreasing both chronotropy and inotropy, while compound 5c is about fivefold more potent in decreasing inotropy than nifedipine. Moreover, compound 5b is the most potent calcium antagonist derivative of the series. Copyright (C) 1996 Elsevier Science Ltd

  DOI：

  10.1016/0968-0896(96)00155-1
• 作为产物：
  描述：

  乙酰乙酸乙酯 、 2,3-二氯苯甲醛 在 ammonium acetate 作用下， 生成 非洛地平杂质C
  参考文献：
  名称：

  用于合成 Hantzsch 1,4-二氢吡啶和药物分子的高度化学稳定性的 3D 互穿 MOF 多相催化剂

  摘要：

  金属有机框架（MOF）作为比其他固体催化剂更高效的多相催化剂而引起了极大的关注，然而，其化学环境的不稳定性往往限制了其催化潜力。在此，利用灵活的未开发的四酸配体并采用混合配体方法，战略性地开发了一种3D互穿的稳健框架IITKGP-51（IITKGP代表印度理工学院卡拉格普尔分校），它在很宽的pH范围内保持其结晶度解决方案（4-12）。 IITKGP-51具有充足的开放金属位点 (OMS)，可作为一锅 Hantzsch 缩合反应中的多相催化剂，且催化剂负载量低，适用于多种底物。药物分子的合成仍然是有机化学和药物化学最重要和最新兴的领域之一。考虑到这种实用性，首次使用该催化剂合成了具有重要生物学意义的Nemadipine B和Nifedipine药物分子（钙通道蛋白抑制剂），并通过SC-XRD和其他光谱方法进行了全面表征。该报告首次使用 MOF 材料作为药物分子合成的催化剂。

  DOI：

  10.1002/smll.202309281

文献信息

• A new In–SiO2 composite catalyst in the solvent-free multicomponent synthesis of Ca2+ channel blockers nifedipine and nemadipine B
  作者：Ricardo F. Affeldt、Edilson V. Benvenutti、Dennis Russowsky

  DOI：10.1039/c2nj40060j

  日期：——

  An In–SiO2 composite was prepared by the sol–gel method and was applied as a heterogeneous Lewis acid catalyst in the multicomponent Hantzsch synthesis of symmetrical and non-symmetrical 1,4-DHPs. The Ca2+ channel blockers nifedipine and nemadipine B were synthesized in a single step through a solvent-free protocol.

  采用溶胶凝胶法制备了一种 InâSiO2 复合材料，并将其用作多组分 Hantzsch 合成对称和非对称 1,4-DHPs 的异相路易斯酸催化剂。通过无溶剂方案，一步合成了钙离子通道阻滞剂硝苯地平和奈马地平 B。
• Process to prepare 1,4-dihydropyridine intermediates and derivatives thereof
  申请人：——

  公开号：US20040204604A1

  公开（公告）日：2004-10-14

  An improved catalyst is disclosed for a process involving the preparation of benzylidene intermediates useful in the preparation of 1,4-dihydropyridine compounds and derivatives thereof useful as medicines such as for example felodipine. This is accomplished by the condensation of an aldehyde and an acetoacetate in the presence of a novel catalyst system that includes a pyridyl carboxylic acid and a secondary amine. It has been found that through the use of the present invention the purity and yield of the desired isomer of the benzylidene intermediate can be maximized, thus avoiding the requirement of additional purification steps. The use of these intermediates can then be further reacted to form the required dihydropyridines, again having a very high purity and yield compared with the prior art.

  本发明公开了一种改进的催化剂，用于涉及制备苄亚甲基中间体的过程，该中间体在制备1,4-二氢吡啶化合物及其衍生物中有用，如例如非洛地平。这是通过在新型催化剂体系的存在下对醛和乙酰乙酸酯进行缩合来实现的，该催化剂体系包括吡啶基羧酸和二级胺。通过使用本发明，发现所需苄亚甲基中间体的异构体的纯度和产率可以最大化，从而避免了额外的纯化步骤的要求。然后可以进一步将这些中间体用于反应形成所需的二氢吡啶，与先前技术相比，其纯度和产率非常高。
• First Report About the Use of Micellar Keggin Heteropolyacids as Catalysts in the Green Multicomponent Synthesis of Nifedipine Derivatives
  作者：Valeria Palermo、Ángel G. Sathicq、Thierry Constantieux、Jean Rodríguez、Patricia G. Vázquez、Gustavo P. Romanelli

  DOI：10.1007/s10562-016-1784-8

  日期：2016.9

  determined by potentiometric titration with n-butylamine. A series of bioactive 1,4-dihydropyridine derivatives such as nifedipine and nemadipine B were synthesized using these new materials, in a one-pot procedure in ethanol. This methodology requires a reaction time of 8 h, and a temperature of 78 °C to obtain good to excellent yields of 1,4-dihydropyridine derivatives. The micellar Keggin catalysts

  胶束 Keggin 杂多酸催化剂使用十六烷基三甲基溴化铵（十六烷基三甲基溴化铵-CTAB）、1-十六烷基氯化吡啶和 Keggin 杂多酸 H3PMo12O40 和 H4PMo11VO40 作为前体制备。制备了四种催化剂（PMo12C16、PMo11VC16、PMo12C16Py和PMo11VC16Py）并通过31P NMR、FT-IR、XRD、SEM分析和结构特性（SBET）进行表征。催化剂的酸性特性通过用正丁胺进行电位滴定来确定。使用这些新材料，在乙醇中的单锅程序中合成了一系列生物活性 1,4-二氢吡啶衍生物，例如硝苯地平和奈马地平 B。该方法需要 8 小时的反应时间和 78 °C 的温度才能获得良好至极好的 1,4-二氢吡啶衍生物收率。胶束 Keggin 催化剂不溶于极性介质，因此可以轻松去除反应产物而不影响其催化活性。浸出试验表明它们具有优异的稳定性，可以作为非均相催化剂使用五次而催
• 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。