Dimethyl 4-[6-(2,5-dimethoxy-4-nitrophenyl)imidazo[2,1-b][1,3]thiazol-5-yl]-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate | 1015756-50-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: Dimethyl 4-[6-(2,5-dimethoxy-4-nitrophenyl)imidazo[2,1-b][1,3]thiazol-5-yl]-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate
• CAS: 1015756-50-9
• 化学式: C₂₄H₂₄N₄O₈S
• 分子量: 528.543
• InChiKey: SMZFRGYJZKEHFJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  37
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  174
• 氢给体数：
  1
• 氢受体数：
  11

反应信息

• 作为产物：
  描述：

  6-(2,5-Dimethoxy-4-nitrophenyl)imidazo[2,1-b][1,3]thiazole-5-carbaldehyde 、 乙酰乙酸甲酯 在 ammonium hydroxide 作用下， 以 异丙醇 为溶剂， 以20%的产率得到Dimethyl 4-[6-(2,5-dimethoxy-4-nitrophenyl)imidazo[2,1-b][1,3]thiazol-5-yl]-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate
  参考文献：
  名称：

  Imidazo[2,1-b]thiazole System: A Scaffold Endowing Dihydropyridines with Selective Cardiodepressant Activity

  摘要：

  The synthesis, characterization, and functional in vitro assays in cardiac tissues and smooth muscle (vascular and nonvascular) of a number of 4-imidazo[2,1-b]thiazole-1,4-dihydropyridines are reported. The binding properties for the novel compounds have been investigated and the interaction with the binding site common to other aryl-dihydropyridines has been demonstrated. Interestingly, the novel 4-aryl-dihydropyridines are L-type calcium channel blockers with a peculiar pharmacological behavior. Indeed, the imidazo[2,1-b]thiazole system is found to confer to the dihydropyridine scaffold an inotropic and/or chronotropic cardiovascular activity with a high selectivity toward the nonvascular tissue. Finally, molecular modeling studies were undertaken for the most representative compounds with the aim of describing the binding properties of the new ligands at molecular level and to rationalize the found structure-activity relationship data. Due to the observed pharmacological behavior of our compounds, they might be promising agents for the treatment of specific cardiovascular pathologies such as cardiac hypertrophy and ischemia.

  DOI：

  10.1021/jm070681+

文献信息

• Ligand Based Approach to L-Type Calcium Channel by Imidazo[2,1-<i>b</i>]thiazole-1,4-Dihydropyridines: from Heart Activity to Brain Affinity
  作者：Alessandra Locatelli、Sandro Cosconati、Matteo Micucci、Alberto Leoni、Luciana Marinelli、Andrea Bedini、Pierfranco Ioan、Santi Mario Spampinato、Ettore Novellino、Alberto Chiarini、Roberta Budriesi

  DOI：10.1021/jm301839q

  日期：2013.5.23

  The synthesis, characterization, and functional in vitro assay in cardiac and smooth muscle (vascular and nonvascular) of a series of 4-imidazo[2,1-b]thiazole-1,4-dihydropyridines are reported. To define the calcium blocker nature of the imidazo[2,1-b]thiazole-1,4-DHPs and their selectivity on Ca(v)1.2 and Ca(v)1.3 isoforms, we performed binding studies on guinea pig atrial and ventricular membranes on intact cells expressing the cloned Ca(v)1.2a subunit and on rat brain cortex. To get major insights into the reasons for the affinity for Ca(v)1.2 and/or Ca(v)1.3, molecular modeling studies were also undertaken. Some physicochemical and pharmacokinetic properties of selected compounds were calculated and compared. All the biological data collected and reported herein allowed us to rationalize the structure-activity relationship of the 4-imidazo[2,1-b]thiazole-1,4-DHPs and to identify which of these enhanced the activity at the central level.