2-<<2-amino>ethoxy>methyl>-4-(2-chlorophenyl)-3-(ethoxycarbonyl)-5-(methoxycarbonyl)-6-methyl-1,4-dihydropyridine | 123700-30-1

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: 2-<<2-amino>ethoxy>methyl>-4-(2-chlorophenyl)-3-(ethoxycarbonyl)-5-(methoxycarbonyl)-6-methyl-1,4-dihydropyridine
• 英文别名: 3-O-ethyl 5-O-methyl 2-[2-[bis(2-methoxy-2-oxoethyl)amino]ethoxymethyl]-4-(2-chlorophenyl)-6-methyl-1,4-dihydropyridine-3,5-dicarboxylate
• CAS: 123700-30-1
• 化学式: C₂₆H₃₃ClN₂O₉
• 分子量: 553.009
• InChiKey: TUBHGUSROCNICA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.96
• 重原子数：
  38.0
• 可旋转键数：
  13.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  129.7
• 氢给体数：
  1.0
• 氢受体数：
  11.0

反应信息

• 作为反应物：
  描述：

  2-<<2-amino>ethoxy>methyl>-4-(2-chlorophenyl)-3-(ethoxycarbonyl)-5-(methoxycarbonyl)-6-methyl-1,4-dihydropyridine 在 ammonium hydroxide 作用下， 以 甲醇 为溶剂， 反应 2.0h， 以64%的产率得到2-<<2-amino>ethoxy>methyl>-4-(2-chlorophenyl)-3-(ethoxycarbonyl)-5-(methoxycarbonyl)-6-methyl-1,4-dihydropyridine
  参考文献：
  名称：

  Long-acting dihydropyridine calcium antagonists. 4. Synthesis and structure-activity relationships for a series of basic and nonbasic derivatives of 2[(2-aminoethoxy)methyl]-1,4-dihydropyridine calcium antagonists

  摘要：

  The preparation of a series of 1,4-dihydropyridines (DHPs) which have polar, acyclic, nonbasic substituents on an ethoxymethyl chain at the 2-position is described. In addition, in order to assess the effects of incorporating a basic center into DHPs of this type, a series of glycinamides were also prepared. The calcium antagonist activity on rat aorta of both these classes of DHP is compared with their negative inotropic activity as determined by using a Langendorff perfused guinea pig heart model. A number of the compounds evaluated have activity of the same order as nifedipine although those with more extended substituents have lower potency, particularly when a basic substituent is present. The compounds examined displayed a wide variation in selectivity for vascular over cardiac tissue. A number of structure-activity relationship trends were identified and possible explanations to account for the differences in selectivity observed are advanced. One of the compounds, 2-[[2-[[4-(2-chlorophenyl)-3-(ethoxycarbonyl)-5-(methoxycarbonyl)-6- methyl-1,4-dihydropyrid-2-yl]methoxy]ethyl]amino]acetamide (26, UK-51,656), was identified as a potent (IC50 = 4 x 10(-9) M) calcium antagonist which is 20-fold selective for vascular over cardiac tissue and which has a markedly longer duration of action (greater than 5 h) than nifedipine in the anesthetized dog on intravenous administration. The pharmacokinetic half-life of 26 was established as 4.7 h and possible explanations are advanced to account for 26 having a shorter plasma half-life than amlodipine and a longer plasma half-life than felodipine.

  DOI：

  10.1021/jm00164a019
• 作为产物：
  描述：

  氨氯地平 、 溴乙酸甲酯 在 potassium carbonate 作用下， 以 乙腈 为溶剂， 反应 2.0h， 以30%的产率得到2-<<2-amino>ethoxy>methyl>-4-(2-chlorophenyl)-3-(ethoxycarbonyl)-5-(methoxycarbonyl)-6-methyl-1,4-dihydropyridine
  参考文献：
  名称：

  Long-acting dihydropyridine calcium antagonists. 4. Synthesis and structure-activity relationships for a series of basic and nonbasic derivatives of 2[(2-aminoethoxy)methyl]-1,4-dihydropyridine calcium antagonists

  摘要：

  The preparation of a series of 1,4-dihydropyridines (DHPs) which have polar, acyclic, nonbasic substituents on an ethoxymethyl chain at the 2-position is described. In addition, in order to assess the effects of incorporating a basic center into DHPs of this type, a series of glycinamides were also prepared. The calcium antagonist activity on rat aorta of both these classes of DHP is compared with their negative inotropic activity as determined by using a Langendorff perfused guinea pig heart model. A number of the compounds evaluated have activity of the same order as nifedipine although those with more extended substituents have lower potency, particularly when a basic substituent is present. The compounds examined displayed a wide variation in selectivity for vascular over cardiac tissue. A number of structure-activity relationship trends were identified and possible explanations to account for the differences in selectivity observed are advanced. One of the compounds, 2-[[2-[[4-(2-chlorophenyl)-3-(ethoxycarbonyl)-5-(methoxycarbonyl)-6- methyl-1,4-dihydropyrid-2-yl]methoxy]ethyl]amino]acetamide (26, UK-51,656), was identified as a potent (IC50 = 4 x 10(-9) M) calcium antagonist which is 20-fold selective for vascular over cardiac tissue and which has a markedly longer duration of action (greater than 5 h) than nifedipine in the anesthetized dog on intravenous administration. The pharmacokinetic half-life of 26 was established as 4.7 h and possible explanations are advanced to account for 26 having a shorter plasma half-life than amlodipine and a longer plasma half-life than felodipine.

  DOI：

  10.1021/jm00164a019

文献信息

• ALKER, DAVID;CAMPBELL, SIMON F.;CROSS, PETER E.;BURGES, ROGER A.;CARTER, +, J. MED. CHEM., 33,(1990) N, C. 585-591
  作者：ALKER, DAVID、CAMPBELL, SIMON F.、CROSS, PETER E.、BURGES, ROGER A.、CARTER, +

  DOI：——

  日期：——