(+/-)-Mebudipine | 103521-70-6

• 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: (+/-)-Mebudipine
• 英文别名: tert-butyl methyl 2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate；nebudipine；Mebudipine；5-O-tert-butyl 3-O-methyl 2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate
• CAS: 103521-70-6
• 化学式: C₂₀H₂₄N₂O₆
• 分子量: 388.42
• InChiKey: YXPRKGBMFPQBDH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  28
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  110
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (+/-)-Mebudipine 在 铁粉 、 氯化铵 作用下， 以 甲醇 为溶剂， 生成 4-(3-Aminophenyl)-1,4-dihydro-2,6-dimethyl-3,5-pyridine-dicarboxylic acid, 1,1-dimethylethyl methyl ester
  参考文献：
  名称：

  Dihydropyridine Neuropeptide Y Y1 Receptor Antagonists

  摘要：

  Dihydropyridine 5a was found to be an inhibitor of neuropeptide Y-1 binding in a high throughput I-125-PYY screening assay. Structure-activity studies around certain portions of the dihydropyridine chemotype identified BMS-193885 (6e) as a potent and selective Y-1 receptor antagonist. In a forskolin-stimulated c-AMP production assay using CHO cells expressing the human Y-1 receptor, 6e demonstrated full functional antagonism (K-b = 4.5 nM). Compound 6e inhibited NPY-induced feeding in satiated rats when dosed at 3.0 and 10.0 mg/kg (ip), and also decreased spontaneous overnight food consumption in rats at doses of 10 and 20 mg/kg (ip). (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(01)00761-2
• 作为产物：
  描述：

  间硝基苯甲醛 、 alkaline earth salt of/the/ methylsulfuric acid 在 哌啶 溶剂黄146 作用下， 以 甲醇 为溶剂， 反应 22.0h， 生成 (+/-)-Mebudipine
  参考文献：
  名称：

  两种新型钙通道阻滞剂美布地平和地布地平的合成和生物活性。

  摘要：

  二氢吡啶衍生物钙通道阻滞剂广泛用于高血压，心绞痛和其他心血管疾病的治疗。因为二氢吡啶衍生物的原型硝苯地平不具有最佳的药代动力学和药效学特性，所以已经尝试合成具有改进性质的此类其他药物。本文描述了两种新的钙通道阻滞剂，硝苯地平的非对称（美布地平）和对称（dibudipine）类似物的合成和生物活性。通过研究其对离体豚鼠回肠和大鼠主动脉环收缩的作用，评估了这些化合物的药理作用。将结果与硝苯地平的结果进行比较。新的类似物和硝苯地平抑制了豚鼠回肠对电刺激的收缩反应，并且化合物的pIC50值没有显着差异。该化合物还拮抗K +去极化的豚鼠回肠对钙的累积浓度的收缩反应。Mebudipine的抑制作用明显高于硝苯地平，而dibudipine和硝苯地平的抑制作用没有差别。所有这三种化合物均松弛了用KCl（40 mM）处理的分离的主动脉环。舒张的pIC50值为：美布地平>硝苯地平>杜布地平。结论是这些新的二氢

  DOI：

  10.1111/j.2042-7158.1997.tb06075.x

文献信息

• Stereochemical Requirements for the Mineralocorticoid Receptor Antagonist Activity of Dihydropyridines
  作者：Graciela B. Arhancet、Scott S. Woodard、Jessica D. Dietz、Danny J. Garland、Grace M. Wagner、Kaliappan Iyanar、Joe T. Collins、James R. Blinn、Randal E. Numann、Xiao Hu、Horng-Chih Huang

  DOI：10.1021/jm1002827

  日期：2010.5.27

  A number of known 1,4-dihydropyridine CCBs were identified as having comparable potency to the steroidal MR antagonist eplerenone. Chiral resolution of mebudipine revealed that MR and CCB activity reside in opposite enantiomers. Small molecule X-ray crystal structures showed that the C4 stereochemistry of optimized selective MR analogues, e.g. 5, is consistent with MR-active mebudipine. Molecular modeling supports a binding pose consistent with that previously proposed for DHP diesters.
• Dihydropyridine Neuropeptide Y Y1 Receptor Antagonists
  作者：Graham S. Poindexter、Marc A. Bruce、Karen L. LeBoulluec、Ivo Monkovic、Scott W. Martin、Eric M. Parker、Larry G. Iben、Rachel T. McGovern、Astrid A. Ortiz、Jennifer A. Stanley、Gail K. Mattson、Michael Kozlowski、Meredith Arcuri、Ildiko Antal-Zimanyi

  DOI：10.1016/s0960-894x(01)00761-2

  日期：2002.2

  Dihydropyridine 5a was found to be an inhibitor of neuropeptide Y-1 binding in a high throughput I-125-PYY screening assay. Structure-activity studies around certain portions of the dihydropyridine chemotype identified BMS-193885 (6e) as a potent and selective Y-1 receptor antagonist. In a forskolin-stimulated c-AMP production assay using CHO cells expressing the human Y-1 receptor, 6e demonstrated full functional antagonism (K-b = 4.5 nM). Compound 6e inhibited NPY-induced feeding in satiated rats when dosed at 3.0 and 10.0 mg/kg (ip), and also decreased spontaneous overnight food consumption in rats at doses of 10 and 20 mg/kg (ip). (C) 2002 Elsevier Science Ltd. All rights reserved.
• Synthesis and Biological Activity of Two New Calcium-channel Blockers, Mebudipine and Dibudipine
  作者：M Mahmoudian、H Mirkhani、Z Nehardani、S Ghiaee

  DOI：10.1111/j.2042-7158.1997.tb06075.x

  日期：2011.4.12

  derivatives, nifedipine, does not have the optimum pharmacokinetic and pharmacodynamic characteristics, attempts have been made to synthesize other drugs in this class with improved properties. The synthesis and biological activity of two new calcium-channel blockers, non-symmetrical (mebudipine) and symmetrical (dibudipine) analogues of nifedipine, is described herein. The pharmacological potencies

  二氢吡啶衍生物钙通道阻滞剂广泛用于高血压，心绞痛和其他心血管疾病的治疗。因为二氢吡啶衍生物的原型硝苯地平不具有最佳的药代动力学和药效学特性，所以已经尝试合成具有改进性质的此类其他药物。本文描述了两种新的钙通道阻滞剂，硝苯地平的非对称（美布地平）和对称（dibudipine）类似物的合成和生物活性。通过研究其对离体豚鼠回肠和大鼠主动脉环收缩的作用，评估了这些化合物的药理作用。将结果与硝苯地平的结果进行比较。新的类似物和硝苯地平抑制了豚鼠回肠对电刺激的收缩反应，并且化合物的pIC50值没有显着差异。该化合物还拮抗K +去极化的豚鼠回肠对钙的累积浓度的收缩反应。Mebudipine的抑制作用明显高于硝苯地平，而dibudipine和硝苯地平的抑制作用没有差别。所有这三种化合物均松弛了用KCl（40 mM）处理的分离的主动脉环。舒张的pIC50值为：美布地平>硝苯地平>杜布地平。结论是这些新的二氢