2,6-Dimethyl-4-[2-(4-methyl-2-oxy-furazan-3-ylmethoxy)-phenyl]-1,4-dihydro-pyridine-3,5-dicarboxylic acid dimethyl ester | 220270-98-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 2,6-Dimethyl-4-[2-(4-methyl-2-oxy-furazan-3-ylmethoxy)-phenyl]-1,4-dihydro-pyridine-3,5-dicarboxylic acid dimethyl ester
• 英文别名: dimethyl 2,6-dimethyl-4-[2-[(4-methyl-2-oxido-1,2,5-oxadiazol-2-ium-3-yl)methoxy]phenyl]-1,4-dihydropyridine-3,5-dicarboxylate
• CAS: 220270-98-4
• 化学式: C₂₁H₂₃N₃O₇
• 分子量: 429.43
• InChiKey: XANHNMPVLVGGJP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  31
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  125
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  2,6-Dimethyl-4-[2-(4-methyl-2-oxy-furazan-3-ylmethoxy)-phenyl]-1,4-dihydro-pyridine-3,5-dicarboxylic acid dimethyl ester 在 三甲氧基磷 作用下， 反应 9.0h， 生成 2,6-Dimethyl-4-[2-(4-methyl-furazan-3-ylmethoxy)-phenyl]-1,4-dihydro-pyridine-3,5-dicarboxylic acid dimethyl ester
  参考文献：
  名称：

  New 1,4-Dihydropyridines Conjugated to Furoxanyl Moieties, Endowed with Both Nitric Oxide-like and Calcium Channel Antagonist Vasodilator Activities

  摘要：

  A series of 4-phenyl-1,4-dihydropyridines substituted at the ortho and meta positions of the phenyl ring with NO-donating furoxan moieties and their non-NO-releasing furazan analogues were synthesized and pharmacologically characterized. The vasodilator activities of these compounds were evaluated on rat aorta and expressed as EC50 values or as EC50iGC values when obtained in the presence of inhibitors of guanylate cyclase methylene blue (MB) and 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-(ODQ). Affinities to 1,4-DHP receptors on Ca2+ channels, expressed as IC50 values, were determined through displacement experiments of [H-3]-nitrendipine on rat cortex homogenates. A linear correlation between IC50 and EC50 values was found for compounds unable to release NO. EC50calcd values for derivatives containing NO-donor moieties, expression of the Ca2+-blocking component of their vasodilator activity, were interpolated on this linear regression. They showed a good correspondence with EC50iGC values determined in the presence of soluble guanylate cyclase inhibitors. Analysis of (EC50EC50)-E-iGC/ ratios provided a useful tool to distinguish well-balanced hybrids from derivatives biased toward Ca2+-blocking or NO-dependent vasodilator activity. A detrimental effect on affinity to the 1,4-DHP receptor, due to substitution at the ortho and meta positions of the 4-phenyl ring, was observed. SAR to explain this effect is proposed.

  DOI：

  10.1021/jm9803267
• 作为产物：
  描述：

  methyl (E)-3-aminocrotonate 、 2-<(4-methylfuroxan-3-yl)methoxy>benzaldehyde 在 三氟乙酸 作用下， 以 乙醇 为溶剂， 反应 3.0h， 生成 2,6-Dimethyl-4-[2-(4-methyl-2-oxy-furazan-3-ylmethoxy)-phenyl]-1,4-dihydro-pyridine-3,5-dicarboxylic acid dimethyl ester
  参考文献：
  名称：

  New 1,4-Dihydropyridines Conjugated to Furoxanyl Moieties, Endowed with Both Nitric Oxide-like and Calcium Channel Antagonist Vasodilator Activities

  摘要：

  A series of 4-phenyl-1,4-dihydropyridines substituted at the ortho and meta positions of the phenyl ring with NO-donating furoxan moieties and their non-NO-releasing furazan analogues were synthesized and pharmacologically characterized. The vasodilator activities of these compounds were evaluated on rat aorta and expressed as EC50 values or as EC50iGC values when obtained in the presence of inhibitors of guanylate cyclase methylene blue (MB) and 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-(ODQ). Affinities to 1,4-DHP receptors on Ca2+ channels, expressed as IC50 values, were determined through displacement experiments of [H-3]-nitrendipine on rat cortex homogenates. A linear correlation between IC50 and EC50 values was found for compounds unable to release NO. EC50calcd values for derivatives containing NO-donor moieties, expression of the Ca2+-blocking component of their vasodilator activity, were interpolated on this linear regression. They showed a good correspondence with EC50iGC values determined in the presence of soluble guanylate cyclase inhibitors. Analysis of (EC50EC50)-E-iGC/ ratios provided a useful tool to distinguish well-balanced hybrids from derivatives biased toward Ca2+-blocking or NO-dependent vasodilator activity. A detrimental effect on affinity to the 1,4-DHP receptor, due to substitution at the ortho and meta positions of the 4-phenyl ring, was observed. SAR to explain this effect is proposed.

  DOI：

  10.1021/jm9803267