氨氯地平杂质29 | 93848-82-9

• 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: 氨氯地平杂质29
• 英文名称: N-acetylamlodipine
• 英文别名: 2-<<2-(N-acetylamino)ethoxy>methyl>-4-(2-chlorophenyl)-3-(ethoxycarbonyl)-5-(methoxycarbonyl)-6-methyl-1,4-dihydropyridine；2-[[2-(N-acetylamino)ethoxy]methyl]-4-(2-chlorophenyl)-3-(ethoxycarbonyl)-5-(methoxycarbonyl)-6-methyl-1,4-dihydropyridine；3-Ethyl 5-Methyl 2-((2-acetamidoethoxy)methyl)-4-(2-chlorophenyl)-6-methyl-1,4-dihydropyridine-3,5-dicarboxylate；3-O-ethyl 5-O-methyl 2-(2-acetamidoethoxymethyl)-4-(2-chlorophenyl)-6-methyl-1,4-dihydropyridine-3,5-dicarboxylate
• CAS: 93848-82-9
• 化学式: C₂₂H₂₇ClN₂O₆
• 分子量: 450.919
• InChiKey: MRDCCTCXJCVQFK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  31
• 可旋转键数：
  11
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  103
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  氨氯地平杂质29 在 lead(IV) acetate 作用下， 以 二氯甲烷 、 溶剂黄146 为溶剂， 反应 20.0h， 以91%的产率得到2-[2-(acetylamino)ethoxymethyl]-3-ethoxycarbonyl-4-(o-chlorophenyl)-5-methoxycarbonyl-6-methylpyridine
  参考文献：
  名称：

  乙酸铅 (IV) 对 Hantzsch 1,4-二氢吡啶的温和、选择性和高产氧化

  摘要：

  描述了在温和的反应条件下用乙酸铅 (IV) 芳构化 1, 4-二氢吡啶。该方法在不同取代吡啶的合成中选择性强、温和且通用。

  DOI：

  10.3987/com-04-10194
• 作为产物：
  描述：

  氨氯地平 、 乙酰辅酶A 在 三乙醇胺 、 乙二胺四乙酸 、 carnitine acetyltransferase 、 arylamine N-acetyltransferase 2*4, wild-type allele 、 乙酰基肉碱 、 1,4-二巯基-2,3-丁二醇 作用下， 以 水 为溶剂， 反应 18.0h， 生成 氨氯地平杂质29
  参考文献：
  名称：

  芳胺 N-乙酰转移酶 NAT2 对内源脂肪胺进行意外乙酰化。

  摘要：

  N-乙酰基转移酶在异生物质（包括临床药物）的失活和清除中发挥着关键作用。NAT2被归类为芳胺N-乙酰转移酶，主要转化芳香胺、羟胺和肼。在此，我们证明人芳胺N-乙酰转移酶 NAT2 也乙酰化脂肪族内源胺。代谢组学分析和化学合成表明，与慢速乙酰化NAT2表型相比，表达快速乙酰化剂NAT2表型的人类细胞系中单乙酰化亚精胺和二乙酰化亚精胺的细胞内浓度增加。NAT2 对单乙酰化亚精胺的区域选择性N 8乙酰化回答了二乙酰亚精胺来源这一长期存在的问题。我们还发现了 NAT2 对结构多样的含烷基胺药物的选择性乙酰化，这可能会导致患者反应的变化。结果表明 NAT2 具有以前未知的功能和潜在的调节作用，我们建议应考虑对该酶进行重新分类。

  DOI：

  10.1002/anie.202005915

文献信息

• Dihydropyridines Potentiate ATP-Induced Currents Mediated by the Full-Length Human P2X5 Receptor
  作者：Ida C. Schiller、Kenneth A. Jacobson、Zhiwei Wen、Aparna Malisetty、Günther Schmalzing、Fritz Markwardt

  DOI：10.3390/molecules27061846

  日期：——

  The P2X5 receptor, an ATP-gated cation channel, is believed to be involved in tumor development, inflammatory bone loss and inflammasome activation after bacterial infection. Therefore, it is a worthwhile pharmacological target to treat the corresponding diseases, especially in minority populations that have a gene variant coding for functional homotrimeric P2X5 channels. Here, we investigated the effects of dihydropyridines on the human full-length P2X5 receptor (hP2X5FL) heterologously expressed in Xenopus oocytes using the two-microelectrode voltage clamp method. Agonist dependency, kinetics and permeation behavior, including Cl− permeability, were similar to hP2X5FL expressed in HEK293 or 1321N1 cells. Additionally, 1,4-dihydropyridines have been shown to interact with various other purinergic receptors, and we have examined them as potential hP2X5 modulators. Of seven commercially available and four newly synthesized dihydropyridines tested at hP2X5FL, only amlodipine exerted an inhibitory effect, but only at a high concentration of 300 µM. Isradipine and—even more—nimodipine stimulated ATP-induced currents in the low micromolar range. We conclude that common dihydropyridines or four new derivatives of amlodipine are not suitable as hP2X5 antagonists, but amlodipine might serve as a lead for future synthesis to increase its affinity. Furthermore, a side effect of nimodipine therapy could be a stimulatory effect on inflammatory processes.

  P2X5受体是一种ATP门控阳离子通道，被认为参与肿瘤发展、炎性骨质流失和细菌感染后的炎症小体激活。因此，它是治疗相应疾病的有价值的药理靶点，尤其是那些具有编码功能同三聚体P2X5通道的基因变异的少数族裔人群。在这里，我们使用两电极电压钳方法，在异种卵母中异种表达的人类全长P2X5受体（hP2X5FL）上研究了二氢吡啶对其的影响。激动剂依赖性、动力学和渗透行为，包括Cl−渗透性，与在HEK293或1321N1细胞中表达的hP2X5FL类似。此外，已经显示1,4-二氢吡啶与各种其他嘌呤受体相互作用，我们已将它们作为潜在的hP2X5调节剂进行了研究。在测试了七种商业上可获得的和四种新合成的二氢吡啶后，只有氨氯地平在高浓度300µM时产生了抑制作用。异丙地平和尼莫地平在低微摩尔范围内刺激了ATP诱导的电流。我们得出结论，常见的二氢吡啶或四个新的氨氯地平衍生物不适合作为hP2X5拮抗剂，但氨氯地平可能作为未来合成的引物来增加其亲和力。此外，尼莫地平治疗的一个副作用可能是对炎症过程的刺激作用。
• Long-acting dihydropyridine calcium antagonists. 4. Synthesis and structure-activity relationships for a series of basic and nonbasic derivatives of 2[(2-aminoethoxy)methyl]-1,4-dihydropyridine calcium antagonists
  作者：David Alker、Simon F. Campbell、Peter E. Cross、Roger A. Burges、Anthony J. Carter、Donald G. Gardiner

  DOI：10.1021/jm00164a019

  日期：1990.2

  The preparation of a series of 1,4-dihydropyridines (DHPs) which have polar, acyclic, nonbasic substituents on an ethoxymethyl chain at the 2-position is described. In addition, in order to assess the effects of incorporating a basic center into DHPs of this type, a series of glycinamides were also prepared. The calcium antagonist activity on rat aorta of both these classes of DHP is compared with their negative inotropic activity as determined by using a Langendorff perfused guinea pig heart model. A number of the compounds evaluated have activity of the same order as nifedipine although those with more extended substituents have lower potency, particularly when a basic substituent is present. The compounds examined displayed a wide variation in selectivity for vascular over cardiac tissue. A number of structure-activity relationship trends were identified and possible explanations to account for the differences in selectivity observed are advanced. One of the compounds, 2-[[2-[[4-(2-chlorophenyl)-3-(ethoxycarbonyl)-5-(methoxycarbonyl)-6- methyl-1,4-dihydropyrid-2-yl]methoxy]ethyl]amino]acetamide (26, UK-51,656), was identified as a potent (IC50 = 4 x 10(-9) M) calcium antagonist which is 20-fold selective for vascular over cardiac tissue and which has a markedly longer duration of action (greater than 5 h) than nifedipine in the anesthetized dog on intravenous administration. The pharmacokinetic half-life of 26 was established as 4.7 h and possible explanations are advanced to account for 26 having a shorter plasma half-life than amlodipine and a longer plasma half-life than felodipine.
• ALKER, DAVID;CAMPBELL, SIMON F.;CROSS, PETER E.;BURGES, ROGER A.;CARTER, +, J. MED. CHEM., 33,(1990) N, C. 585-591
  作者：ALKER, DAVID、CAMPBELL, SIMON F.、CROSS, PETER E.、BURGES, ROGER A.、CARTER, +

  DOI：——

  日期：——
• Unexpected Acetylation of Endogenous Aliphatic Amines by Arylamine <i>N</i> ‐Acetyltransferase NAT2
  作者：Louis P. Conway、Veronica Rendo、Mário S. P. Correia、Ingvar A. Bergdahl、Tobias Sjöblom、Daniel Globisch

  DOI：10.1002/anie.202005915

  日期：2020.8.17

  play critical roles in the deactivation and clearance of xenobiotics, including clinical drugs. NAT2 has been classified as an arylamine N‐acetyltransferase that mainly converts aromatic amines, hydroxylamines, and hydrazines. Herein, we demonstrate that the human arylamine N‐acetyltransferase NAT2 also acetylates aliphatic endogenous amines. Metabolomic analysis and chemical synthesis revealed increased

  N-乙酰基转移酶在异生物质（包括临床药物）的失活和清除中发挥着关键作用。NAT2被归类为芳胺N-乙酰转移酶，主要转化芳香胺、羟胺和肼。在此，我们证明人芳胺N-乙酰转移酶 NAT2 也乙酰化脂肪族内源胺。代谢组学分析和化学合成表明，与慢速乙酰化NAT2表型相比，表达快速乙酰化剂NAT2表型的人类细胞系中单乙酰化亚精胺和二乙酰化亚精胺的细胞内浓度增加。NAT2 对单乙酰化亚精胺的区域选择性N 8乙酰化回答了二乙酰亚精胺来源这一长期存在的问题。我们还发现了 NAT2 对结构多样的含烷基胺药物的选择性乙酰化，这可能会导致患者反应的变化。结果表明 NAT2 具有以前未知的功能和潜在的调节作用，我们建议应考虑对该酶进行重新分类。
• Mild, Selective and High-Yield Oxidation of Hantzsch 1,4-Dihydropyridines with Lead(IV) Acetate
  作者：Mladen Litvić、Ivica Cepanec、Mirela Filipan、Karmen Kos、Anamarija Bartolinčić、Vinka Drušković、Mohamed Majed Tibi、Vladimir Vinković

  DOI：10.3987/com-04-10194

  日期：——

  Aromatization of 1, 4-dihydropyridines with lead(IV) acetate under mild reaction conditions is described. The method is very selective, mild and versatile in the synthesis of different substituted pyridines.

  描述了在温和的反应条件下用乙酸铅 (IV) 芳构化 1, 4-二氢吡啶。该方法在不同取代吡啶的合成中选择性强、温和且通用。