di(phenylpropyl) 4-(4-chloro-1H-imidazol-5-yl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate | 1342885-02-2

• 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: di(phenylpropyl) 4-(4-chloro-1H-imidazol-5-yl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate
• 英文别名: bis(3-phenylpropyl) 4-(4-chloro-1H-imidazol-5-yl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate
• CAS: 1342885-02-2
• 化学式: C₃₀H₃₂ClN₃O₄
• 分子量: 534.055
• InChiKey: JYSXMMNBILWKHC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.3
• 重原子数：
  38
• 可旋转键数：
  13
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  93.3
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  3-苯丙醇 在 ammonium acetate 作用下， 以 甲醇 、 5,5-dimethyl-1,3-cyclohexadiene 为溶剂， 反应 26.0h， 生成 di(phenylpropyl) 4-(4-chloro-1H-imidazol-5-yl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate
  参考文献：
  名称：

  含 4(5)-chloro-5(4)-imidazolyl 取代基的新型 1,4-dihydropyridines 作为新型钙通道阻滞剂的设计与合成

  摘要：

  设计、合成了硝苯地平的新类似物，其中 4 位的邻硝基苯基已被 4(5)-氯-5(4)-咪唑基取代，并且能够通过氢键与受体相互作用，并评估为钙通道拮抗剂。设计的二氢吡啶是使用 Hantzsch 缩合合成的，并使用豚鼠回肠纵向平滑肌的高 K+ 收缩评估为钙通道拮抗剂。使用 AutoDock4 程序进行对接研究，并使用多元线性回归获得 QSAR 方程。我们的计算研究表明，酯的氧 (O10) 和咪唑环的 N3' 分别与 HIS 363 的 NH 和 LYS354 的 NH 形成氢键相互作用，BEHp5 和 RDF075p 的总和是最重要的描述符。钙通道拮抗剂评估的结果表明，增加 C3 和 C5 酯取代基的链长会增加活性。最有效的化合物是双苯丙酯 (5l) 衍生物，因为它比参考药物硝苯地平的活性更强，而且双苯乙酯 (5k) 衍生物的活性与硝苯地平相当。目前的研究表明，4(5)-氯-5(4)-咪唑基部

  DOI：

  10.1007/s12272-011-0902-9

文献信息

• Molecular modeling and protection against pentylenetetrazole-induced seizure of new 1,4-dihydropyridines containing 5(4)-imidazolyl substituent
  作者：Asghar Davood、Hamed Shafaroodi、Maryam Iman、Abbas Shafiee

  DOI：10.1007/s00044-011-9904-x

  日期：2012.11

  A group of symmetrical and asymmetrical esters of nifedipine analogs, in which the ortho-nitro phenyl group at position 4 was replaced by 2-ethyl(or H)-4(5)-chloro-5(4)-imidazolyl substituent, was designed and evaluated as anticonvulsant against pentylenetetrazole (PTZ)-induced seizure. Our molecular modeling studies reveals that 4-chloro tautomeric form is the main one and has good compatibility with nifedipine and that 4-H is syn-perpendicular. Docking studies reveal that the oxygen atoms of carbonyl group and the N3' of imidazole ring of dihydropyridine form a hydrogen-bonding interaction with the receptor. The time-course of anticonvulsant' effect on PTZ-induced seizure threshold was assessed, and it showed that increasing the lipophilicity decreases the time need for maximum effect. All those mice, treated with intraperitoneal injection of 5, 10, and 20 mg/kg of these derivatives, exhibited increased seizure threshold as compared with control. Based on in vivo results of symmetrical and unsymmetrical ester series, increasing the length of the chain in C3- and C5-ester substituents increases the protection activity. The most active compounds were 2c and 3b, which were more active than the reference drug nifedipine, and compound 2e had comparable activity with nifedipine. QSAR studies indicate that size, hydrophobicity, and topology of DHPs have main effects in the respective biological activities of these compounds.
• Design and synthesis of new 1,4-dihydropyridines containing 4(5)-chloro-5(4)-imidazolyl substituent as a novel calcium channel blocker
  作者：Maryam Iman、Asghar Davood、Ali Reza Nematollahi、Ahmad Rerza Dehpoor、Abbas Shafiee

  DOI：10.1007/s12272-011-0902-9

  日期：2011.9

  New analogues of nifedipine, in which the ortho-nitro phenyl group at position 4 has been replaced by 4(5)-chloro-5(4)-imidazolyl substituent and which are able to interact with the receptor by hydrogen binding were designed, synthesized, and evaluated as calcium channel antagonists. The designed dihydropyridines were synthesized using the Hantzsch condensation and evaluated as calcium channel antagonists

  设计、合成了硝苯地平的新类似物，其中 4 位的邻硝基苯基已被 4(5)-氯-5(4)-咪唑基取代，并且能够通过氢键与受体相互作用，并评估为钙通道拮抗剂。设计的二氢吡啶是使用 Hantzsch 缩合合成的，并使用豚鼠回肠纵向平滑肌的高 K+ 收缩评估为钙通道拮抗剂。使用 AutoDock4 程序进行对接研究，并使用多元线性回归获得 QSAR 方程。我们的计算研究表明，酯的氧 (O10) 和咪唑环的 N3' 分别与 HIS 363 的 NH 和 LYS354 的 NH 形成氢键相互作用，BEHp5 和 RDF075p 的总和是最重要的描述符。钙通道拮抗剂评估的结果表明，增加 C3 和 C5 酯取代基的链长会增加活性。最有效的化合物是双苯丙酯 (5l) 衍生物，因为它比参考药物硝苯地平的活性更强，而且双苯乙酯 (5k) 衍生物的活性与硝苯地平相当。目前的研究表明，4(5)-氯-5(4)-咪唑基部