1,4-dihydro-2,6-dimethyl-4-(pyridin-2-yl)pyridine-3,5-dicarboxylic acid dimethyl ester | 23125-32-8

• 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: 1,4-dihydro-2,6-dimethyl-4-(pyridin-2-yl)pyridine-3,5-dicarboxylic acid dimethyl ester
• 英文别名: 2,6-dimethyl-4-(2-pyridyl)-1,4-dihydropyridine-3,5-dicarboxylic acid dimethyl ester；2,6-dimethyl-3,5-dimethoxycarbonyl-4-(2-pyridyl)-1,4-dihydropyridine；3,5-dimethyl 2,6-dimethyl-4-(2'-pyridyl)-1,4-dihydropyridine-3,5-dicarboxylate；2',6'-dimethyl-1',4'-dihydro-[2,4']bipyridinyl-3',5'-dicarboxylic acid dimethyl ester；1,4-dihydro-2,6-dimethyl-4-(2-pyridyl)pyridine-3,5-dicarboxylic acid dimethyl ester；Dimethyl 1,4-dihydro-2,6-dimethyl-4-(2-pyridyl)pyridine-3,5-dicarboxylate；dimethyl 2,6-dimethyl-4-pyridin-2-yl-1,4-dihydropyridine-3,5-dicarboxylate
• CAS: 23125-32-8
• 化学式: C₁₆H₁₈N₂O₄
• 分子量: 302.33
• InChiKey: DJCQWHDYLUBTRW-UHFFFAOYSA-N

物化性质

• 熔点：
  239-241 °C
• 沸点：
  443.5±45.0 °C(Predicted)
• 密度：
  1.191±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  22
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  77.5
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  1,4-dihydro-2,6-dimethyl-4-(pyridin-2-yl)pyridine-3,5-dicarboxylic acid dimethyl ester 在 sodium tetrahydroborate 作用下， 以 乙醇 、 水 、 丙酮 为溶剂， 反应 12.0h， 生成 dimethyl 1,1',2,3,4',6-hexahydro-1,2,6'-trimethyl<2,4'-bipyridine>-3',5'-dicarboxylate
  参考文献：
  名称：

  Synthesis and calcium channel antagonist activity of dialkyl hexahydro-1,2′,6′-trimethyl[bipyridine]-3′,5′-dicarboxylates

  摘要：

  DOI：

  10.1016/0223-5234(87)90289-3
• 作为产物：
  描述：

  吡啶-2-甲醛 、 乙酰乙酸甲酯 在 zinc ferrite 、 ammonium acetate 作用下， 以 水 为溶剂， 反应 0.5h， 以90%的产率得到1,4-dihydro-2,6-dimethyl-4-(pyridin-2-yl)pyridine-3,5-dicarboxylic acid dimethyl ester
  参考文献：
  名称：

  非均相双金属ZnFe 2 O 4纳米粉末在水中催化合成Hantzsch 1,4-二氢吡啶

  摘要：

  已发现混合金属氧化物ZnFe 2 O 4纳米粉，双路易斯酸碱混合催化剂可有效催化水中的醛，乙酰乙酸乙酯和乙酸铵的多组分合成1,4-二氢吡啶。该程序具有许多优点，包括高收率，较短的反应时间，简单的后处理程序以及良好的生态足迹。该方法利用以下事实：将水，绿色溶剂与ZnFe 2 O 4纳米颗粒结合使用作为催化剂，可以容易地磁性回收并重新用于进一步运行。

  DOI：

  10.1016/j.tetlet.2016.07.071

文献信息

• Chemical compounds having ion channel blocking activity for the treatment of immune dysfunction
  申请人：——

  公开号：US20020119989A1

  公开（公告）日：2002-08-29

  The present invention relates to chemical compounds having inhibitory activity on an intermediate conductance Ca 2+ activated potassium channel (IK Ca), and the use of such compounds for the treatment or alleviation of diseases or conditions relating to immune dysfunction. Moreover, the invention relates to a method of screening a chemical compound for inhibitory activity on an intermediate conductance Ca 2+ activated potassium channel (IK Ca).

  本发明涉及具有对中间电导性Ca2+激活钾通道（IK Ca）具有抑制活性的化合物，以及利用这种化合物治疗或缓解与免疫功能紊乱相关的疾病或症状。此外，本发明涉及一种筛选化合物对中间电导性Ca2+激活钾通道（IK Ca）具有抑制活性的方法。
• Experimental and theoretical structural study of 2-pyridyl- and 4-hydroxyphenyl-1,4-dihydropyridine derivatives
  作者：Héctor Novoa De Armas、Norbert Blaton、Oswald M. Peeters、Camiel De Ranter、Margarita Suárez、Emilio Rolando、Yamila Verdecia、Estael Ochoa、Nazario Martín、Margarita Quinteiro、Carlos Seoane、José L. Soto

  DOI：10.1002/jhet.5570370627

  日期：2000.11

  symmetrical 1,4-DHP. The structures of these compounds have been thoroughly studied by X-ray crystallographic analysis and semiempirical (AMI) calculations. A good agreement is found between the theoretical and experimental results. In all cases, the most stable conformation fulfils all the requirements needed for exhibiting an antagonist calcium effect.

  按照众所周知的对称1,4-DHP的Hantzsch程序合成了一系列取代的1,4-二氢吡啶（1,4-DHP）。这些化合物的结构已通过X射线晶体学分析和半经验（AMI）计算进行了深入研究。在理论和实验结果之间找到了很好的一致性。在所有情况下，最稳定的构象均满足显示拮抗剂钙效应所需的所有要求。
• Synthesis and calcium channel antagonist activity of dialkyl 1,4-dihydro-2,6-dimethyl-4-(pyridinyl)-3,5-pyridinedicarboxylates
  作者：Lina Dagnino、Moy Cheong Li-Kwong-Ken、Michael W. Wolowyk、Hla Wynn、Christopher R. Triggle、Edward E. Knaus

  DOI：10.1021/jm00162a016

  日期：1986.12

  3-aminocrotonate (4) and pyridinecarboxaldehydes 5 afforded the unsymmetrical alkyl methyl 1,4-dihydro-2,6-dimethyl-4-(pyridinyl)-3,5-pyridinedicarboxylates 6, whereas condensation of 3 with 5 and ammonium hydroxide gave the symmetrical dialkyl 1,4-dihydro-2,6-dimethyl-4-(pyridinyl)-3,5-pyridinedicarboxylates 7. The calcium channel antagonist activities of disubstituted 1,4-dihydro-3,5-pyridinedicarboxylates

  乙酰乙酸烷基酯3与3-氨基巴豆酸甲酯（4）和吡啶甲醛5的汉茨缩合反应得到不对称的1,4-二氢-2,6-二甲基-4-（吡啶基）-3,5-吡啶二甲酸烷基甲基酯6，而缩合反应3与5和氢氧化铵反应得到对称的1,4-二氢-2,6-二甲基-4-（吡啶基）-3,5-吡啶二羧酸二烷基酯7。二取代的1,4-二氢-3的钙通道拮抗剂活性使用豚鼠回肠纵向平滑肌的毒蕈碱受体介导的Ca2 +依赖性收缩测定1,5-吡啶二甲酸6,7和9。异构吡啶基类似物6和7的相对效价顺序是2-吡啶基大于3-吡啶基大于4-吡啶基。增加烷基酯取代基的大小可增强活性。具有相同酯取代基的化合物比具有相同酯取代基的化合物更有效。用氰基取代基代替C-3和/或C-5酯取代基明显降低了活性。观察到抑制[3H]硝苯地平结合的IC50值与抑制毒蕈碱诱导的收缩反应的补品成分之间的近似1：1关系。测试结果表明4-（吡啶基）取代基在1,4-二氢吡啶环系统上具有
• Reduced pyridyl derivatives with cardiovascular regulating properties
  申请人：University of Alberta

  公开号：US04771057A1

  公开（公告）日：1988-09-13

  Pharmaceutical compounds of the general formula (1): ##STR1## have been prepared and non-toxic pharmaceutically acceptable salts thereof, wherein the ring system is a 1,2- or 1,4-dihydropyridyl radical; R.sub.1 is a hydrogen, lower alkyl, lower alkyl carbonyl or lower alkoxy carbonyl substituent; R.sub.2 is a lower alkly or phenyl substituent; R.sub.3 is a lower alkoxy carbonyl, (N,N-lower dialkylamino) lower alkoxy carbonyl, (N-lower alkyl-N-phenyl lower alkyl amino) lower alkoxy carbonyl, lower alkoxy lower alkoxy carbonyl, nitro, or cyano substituent; R.sub.4 is a member selected from the group consisting of pyridyl, N-lower alkoxy carbonyl-1,2-dihydropyridyl, N-lower alkyl carbonyl-1,2-dihydropyridyl, N-phenyloxy carbonyl-1,2-dihydropyridyl, N-lower alkoxy carbonyl-1,6-dihydropyridyl, N-lower alkyl carbonyl-1,6-dihydropyridyl, N-lower alkyl carbonyl-1,6-dihydropyridyl, N-phenyloxy carbonyl-1,6-dihydropyridyl, N-lower alkoxy carbonyl-1,4-dihydropyridyl, N-lower alkyl carbonyl-1,4-dihydropyridyl, N-phenyloxy carbonyl-1,4-dihydropyridyl, N-lower alkyl 1,2,3,6-tetrahydropyridyl, N-lower alkoxy carbonyl-1,2,3,6-tetrahydropyridyl, N-lower alkyl carbonyl-1,2,3,6-tetrahydropyridyl, nitro substituted phenyl or trifluoromethyl substituted phenyl; R.sub.5 is a lower alkoxy carbonyl, (N,N-lower dialkylamino) lower alkoxy carbonyl, (N-lower alkyl-N-phenyl lower alkyl amino) lower alkoxy carbonyl, lower alkoxy lower alkoxy carbonyl, nitro, or cyano substitutent; R.sub.6 is a lower alkyl, or phenyl substituent, lower denoting a straight or branched chain having from 1-6 carbon atoms. These compounds regulate cardiovascular activity due to their ability to induce cerebral and peripheral vasodilation, decrease heart rate, and/or increase cardiac contractility, and are useful in the treatment of angina, arrhythmias, cerebralvascular disease and hypertension.

  通用公式（1）的药物化合物已经制备出来，以及其非毒性的药用可接受盐，其中环系统是1,2-或1,4-二氢吡啶基；R.sub.1是氢、低烷基、低烷基羰基或低烷氧羰基取代基；R.sub.2是低烷基或苯基取代基；R.sub.3是低烷氧羰基、（N,N-低二烷基氨基）低烷氧羰基、（N-低烷基-N-苯基低烷基氨基）低烷氧羰基、低烷氧低烷氧羰基、硝基或氰基取代基；R.sub.4是从吡啶基、N-低烷氧羰基-1,2-二氢吡啶基、N-低烷基羰基-1,2-二氢吡啶基、N-苯氧羰基-1,2-二氢吡啶基、N-低烷氧羰基-1,6-二氢吡啶基、N-低烷基羰基-1,6-二氢吡啶基、N-低烷基羰基-1,6-二氢吡啶基、N-苯氧羰基-1,6-二氢吡啶基、N-低烷氧羰基-1,4-二氢吡啶基、N-低烷基羰基-1,4-二氢吡啶基、N-苯氧羰基-1,4-二氢吡啶基、N-低烷基-1,2,3,6-四氢吡啶基、N-低烷氧羰基-1,2,3,6-四氢吡啶基、N-低烷基羰基-1,2,3,6-四氢吡啶基、硝基取代苯基或三氟甲基取代苯基中选择的成员；R.sub.5是低烷氧羰基、（N,N-低二烷基氨基）低烷氧羰基、（N-低烷基-N-苯基低烷基氨基）低烷氧羰基、低烷氧低烷氧羰基、硝基或氰基取代基；R.sub.6是低烷基或苯基取代基，低表示由1-6个碳原子组成的直链或支链。这些化合物通过其诱导脑部和周围血管扩张、降低心率和/或增加心脏收缩力的能力，调节心血管活动，并且在治疗心绞痛、心律失常、脑血管疾病和高血压方面是有用的。
• Antihypertensive reduced pyridyl derivatives
  申请人：The Governors of the University of Alberta

  公开号：EP0239186A1

  公开（公告）日：1987-09-30

  Pharmaceutical compounds of the general formula (1): have been prepared and non-toxic pharmaceutically acceptable salts thereof, wherein the ring system is a 1,2- or 1,4-dihydropyridyl radical; R1 is a hydrogen, lower alkyl, lower alkyl carbonyl or lower alkoxy carbonyl substituent; R2 is a lower alkyl or phenyl substituent; R3 is a lower alkoxy carbonyl, (N,N-lower dialkylamino) lower alkoxy carbonyl, (N-loweralkyl-N-phenyl lower alkyl amino) lower alkoxy carbonyl, lower alkoxy lower alkoxy carbonyl, nitro or cyano substituent; R4 is a member selected from the group consisting of pyridyl, N-lower alkoxy carbonyl-1,2-dihydropyridyl, N-lower alkyl carbonyl-1,2-dihydropyridyl, N-phenyloxy carbonyl-1,2-dihydropyridyl, N-lower alkoxy carbonyl-1,6-dihydropyridyl, N-lower alkyl carbonyl-1,6-dihydropyridyl, N-lower alkyl carbonyl-1,6-dihydropyridyl, N-phenyloxy carbonyl-1,6-dihydropyridyl, N-lower alkoxy carbonyl-1,4-dihydropyridyl, N-lower alkyl carbonyl-1,4-dihydropyridyl, N-phenyloxy carbonyl-1,4-dihydropyridyl, N-lower alkyl 1,2,3,6-tetrahydropyridyl, N-lower alkoxy carbonyl-1,2,3,6-tetrahydropyridyl, N-lower alkyl carbonyl-1,2,3,6-tetrahydropyridyl, nitro substituted phenyl or trifluoromethyl substituted phenyl; Rs is a lower alkoxy carbonyl, (N,N-lowerdialkylamino) lower alkoxycarbonyl, (N-loweralkyl-N-phenyl lower alkyl amino) lower alkoxy carbonyl, lower alkoxy lower alkoxy carbonyl, nitro, or cyano substitutent; R6 is a lower alkyl, or phenyl substituent, lower denoting a straight or branched chain having from 1-6 carbon atoms. The compounds exhibit antihypertensive activity due to their ability to induce cerebral and peripheral vasodilation, decrease heart rate, and/or increase cardiac contractility, and are useful in the treatment of angina, arrhythmias, cerebralvascular disease and hypertension.

  通式(1)的药用化合物： 已制备出的药物化合物及其无毒的药学上可接受的盐，其中环系统是 1，2-或 1，4-二氢吡啶基；R1 是氢、低级烷基、低级烷基羰基或低级烷氧基羰基取代基；R2 是低级烷基或苯基取代基；R3 是低级烷氧基羰基、（N，N-低级二烷基氨基）低级烷氧基羰基、（N-低级烷基-N-苯基低级烷基氨基）低级烷氧基羰基、低级烷氧基低级烷氧基羰基、硝基或氰基取代基；R4 是选自吡啶基、N-低级烷氧基羰基-1,2-二氢吡啶基、N-低级烷基羰基-1,2-二氢吡啶基、N-苯基氧基羰基-1,2-二氢吡啶基、N-低级烷氧基羰基-1,6-二氢吡啶基、N-低级烷基羰基-1,6-二氢吡啶基、N-低级烷基羰基-1,6-二氢吡啶基、N-苯基氧基羰基-1、6-二氢吡啶基、N-低级烷氧基羰基-1,4-二氢吡啶基、N-低级烷基羰基-1,4-二氢吡啶基、N-苯氧基羰基-1,4-二氢吡啶基、N-低级烷基 1,2,3、1,2,3,6-四氢吡啶基、N-低级烷氧基羰基-1,2,3,6-四氢吡啶基、N-低级烷基羰基-1,2,3,6-四氢吡啶基、硝基取代的苯基或三氟甲基取代的苯基；Rs 是低级烷氧基羰基、（N,N-低级二烷基氨基）低级烷氧基羰基、（N-低级烷基-N-苯基低级烷基氨基）低级烷氧基羰基、低级烷氧基低级烷氧基羰基、硝基或氰基取代基；R6 是低级烷基或苯基取代基，低级表示具有 1-6 个碳原子的直链或支链。这些化合物具有抗高血压活性，因为它们能够诱导脑血管和外周血管扩张、降低心率和/或增加心脏收缩力，可用于治疗心绞痛、心律失常、脑血管疾病和高血压。