2,6-二甲基-4-(2-硝基苯基)-1,4-二氢-3,5-吡啶二甲酸甲乙酯 | 53055-15-5

• 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: 2,6-二甲基-4-(2-硝基苯基)-1,4-二氢-3,5-吡啶二甲酸甲乙酯
• 中文别名: 硝苯地平杂质F
• 英文名称: 3-ethyl 5-methyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate
• 英文别名: 2,6-dimethyl-4-(2'-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylic acid 3-methyl ester 5-ethyl ester；methyl ethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate；1,4-dihydro-2,6-dimethyl-4-(2-nitrophenyl)pyridine-3,5-dicarboxylic acid ethyl methyl ester；4-(2-nitro)phenyl-2,6-dimethyl-3-carboethoxy-5-carbomethoxy-1,4-dihydropyridine；2,6-Dimethyl-4-(2'-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylic acid 3-ethyl ester-5-methyl ester；5-O-ethyl 3-O-methyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate
• CAS: 53055-15-5
• 化学式: C₁₈H₂₀N₂O₆
• 分子量: 360.367
• InChiKey: ZZVDQTCQGYISLQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  26
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  110
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  ethyl 5-(2-nitrophenyl)-3-oxo-4-pentenoate 、 aminocrotonic acid methyl ester 以 乙醇 为溶剂， 以58%的产率得到2,6-二甲基-4-(2-硝基苯基)-1,4-二氢-3,5-吡啶二甲酸甲乙酯
  参考文献：
  名称：

  Pharmaceutical compositions containing unsymmetrical esters of

  摘要：

  含有不对称酯化的1,4-二氢吡啶-3,5-二羧酸的药物组合物作为活性成分，并使用方法。所述成分是在二氢吡啶核的4位被苯基取代的不对称1,4-二氢吡啶-3,5-二羧酸酯，该苯基含有至少一个硝基、氰基、叠氮基、烷基硫醚或烷基磺酰基取代基。这些组合物具有心血管活性，可用于促进冠状血管扩张，并且在治疗高血压方面具有用途。

  公开号：

  US03932645A1

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。
• [EN] PROCESS FOR THE PREPARATION OF 1,4-DIHYDROPYRIDINES AND NOVEL 1,4-DIHYDROPYRIDINES USEFUL AS THERAPEUTIC AGENTS<br/>[FR] PROCEDE DE PREPARATION DE 1,4-DIHYDROPYRIDINES ET NOUVELLES 1,4-DIHYDROPYRIDINES UTILES EN TANT QU'AGENTS THERAPEUTIQUES
  申请人：COUNCIL SCIENT IND RES

  公开号：WO2003099790A1

  公开（公告）日：2003-12-04

  The present invention provides a process for the preparation of 1,4-dihydropyridines of the formula (1), wherein R1 is H, NO2, Cl, OAc, OH, R2 is H, NO2, Cl, -O-CH2-O-, OMe, OAc, OEt, OH, R3 is H, NO2, Cl, N(Me)2, -O- CH2 -O-, OMe, OAc, OH, R4 is H, OMe, OAc, OH, R5 is H, Cl, I, and R6 and R7 are either methyl, ethyl or both by preparing a mixture of an aromatic aldehyde, alkyl acetoacetate and a source of ammonia, adsorbing the prepared mixture and adsorbent till adsorbent becomes free flowing, heating the material so obtained under microwave irradiation, cooling the reaction mixture and recovering the compound of formula (1). The present invention also relates to novel 1,4-dihydropyridines with cardiovascular activity.

  本发明提供了一种制备1,4-二氢吡啶的方法，其化学式为（1），其中R1为H、NO2、Cl、OAc、OH，R2为H、 、Cl、-O-CH2-O-、OMe、OAc、OEt、OH，R3为H、 、Cl、N(Me)2、-O- -O-、OMe、OAc、OH，R4为H、OMe、OAc、OH，R5为H、Cl、I，R6和R7为甲基、乙基或两者的混合物，通过制备芳香醛、醋酸烯酮酯和氨源的混合物，吸附制备的混合物和吸附剂直至吸附剂变得自由流动，加热所得材料在微波辐射下，冷却反应混合物，并回收化合物的方法。该发明还涉及具有心血管活性的新型1,4-二氢吡啶。
• Synthesis, Docking Simulation, Biological Evaluations and 3D-QSAR Study of 1,4-Dihydropyridines as Calcium Channel Blockers
  作者：Tarek Fathy El-Moselhy、Peter Ayoub Sidhom、Eman Ahmed Esmat、Nageh Ahmed El-Mahdy

  DOI：10.1248/cpb.c17-00186

  日期：——

  chelating effects of the C3 and C5 substituents. Bulky groups interfere with ring-to-ring hydrophobic interaction with tyrosine (Tyr)4311 and limit the efficiency of increasing the length of the hydrocarbon chain of esters at the 3- and 5-positions of the DHP ring as an approach to increasing the activity. The presence of a chelating substituent on the phenyl ring at the 4-position of the DHP ring ensures

  通过合成保留邻位或间位硝基苯环的两个系列硝苯地平类似物，已恢复了对靶L型电压依赖性钙通道的作用。对受体模型进行了先合成后的分子对接研究，然后进行分子比对，对47种化合物进行了预测，以预测活性最高的成员。IC50值表明某些化合物与硝苯地平相似或更具活性。在二氢吡啶（DHP）环的3位和5位上取代基团得到3k，它比硝苯地平更具活性。我们有效的三维定量构效关系（3D-QSAR）模型预示了亲脂性，蓬松度和C3和C5取代基的螯合效应的影响。庞大的基团会干扰酪氨酸（Tyr）4311的环对环疏水相互作用，并限制增加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方法。DHP环的4位上苯环上的螯合取代基的存在可确保与受体的牢固结合，从而确保闭通道构象的稳定。3D-QSAR模型的验证表明其在预测属于同一化学类别的新化合物的活性方面的熟练程度。DHP环的4位上苯环上的螯合取代基的存在可确保与受体的牢固结
• Process for the preparation of 1,4 - dihydropyridines and novel 1,4-dihydropyridines useful as therapeutic agents
  申请人：COUNCIL OF SCIENTIFIC AND INDUSTRIAL RESEARCH

  公开号：US20030230478A1

  公开（公告）日：2003-12-18

  The present invention provides a process for the preparation of 1,4-dihydropyridines of the formula 1 1 wherein R 1 is H, NO 2 , Cl, OAc, OH, R 2 is H, NO 2 , Cl, —O—CH 2 —O—, OMe, OAc, OEt, OH, R 3 is H, NO 2 , Cl, N(Me) 2 , —O—CH 2 —O—, OMe, OAc, OH, R 4 is H, OMe, OAc, OH, R 5 is H, Cl, I, and R 6 and R 7 are either methyl, ethyl or both by preparing a mixture of an aromatic aldehyde, alkyl acetoacetate and a source of ammonia, adsorbing the prepared mixture on adsorbent till adsorbent becomes free flowing, heating the material so obtained under microwave irradiation, cooling the reaction mixture and recovering the compound of formula I. The present invention also relates to novel 1,4-dihydropyridines.

  本发明提供了一种制备式11中R1为H、NO2、Cl、OAc、OH，R2为H、 、Cl、—O—CH2—O—、OMe、OAc、OEt、OH，R3为H、 、Cl、N(Me)2、—O— —O—、OMe、OAc、OH，R4为H、OMe、OAc、OH，R5为H、Cl、I，R6和R7为甲基、乙基或两者的1,4-二氢吡啶的制备方法，包括制备芳香醛、醋酸酯和氨源的混合物，将制备好的混合物吸附在吸附剂上直至吸附剂变得自由流动，将所得材料在微波辐射下加热，冷却反应混合物并回收式I的化合物。本发明还涉及新型的1,4-二氢吡啶。
• Combinatorial synthesis and screening of a chemical library of 1,4-dihydropyridine calcium channel blockers
  作者：Mikhail F. Gordeev、Dinesh V. Patel、Bruce P. England、Supriya Jonnalagadda、Jesse D. Combs、Eric M. Gordon

  DOI：10.1016/s0968-0896(98)00048-0

  日期：1998.7

  Solid-phase synthesis of a 300-member pharmacophore library of 1,4-dihydropyridines from keto ester, diketone and aldehyde building blocks on a cleavable amine polymeric support is described. Screening and serial deconvolution of the combinatorial library has resulted in identification of known and new potent calcium channel blockers.

  描述了在可裂解的胺聚合物载体上由酮酯，二酮和醛结构单元固相合成1,4-二氢吡啶的300人药效团数据库。组合文库的筛选和连续反卷积已导致鉴定出已知和新的有效钙通道阻滞剂。