3-O-methyl 5-O-(2-methylpropyl) 2,6-dimethyl-4-(1-phenoxycarbonyl-2H-pyridin-4-yl)-1,4-dihydropyridine-3,5-dicarboxylate | 106457-78-7

• 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: 3-O-methyl 5-O-(2-methylpropyl) 2,6-dimethyl-4-(1-phenoxycarbonyl-2H-pyridin-4-yl)-1,4-dihydropyridine-3,5-dicarboxylate
• CAS: 106457-78-7
• 化学式: C₂₆H₃₀N₂O₆
• 分子量: 466.534
• InChiKey: ABVITGXCXRRBPE-UHFFFAOYSA-N

物化性质

• 熔点：
  168-169 °C
• 沸点：
  592.6±50.0 °C(Predicted)
• 密度：
  1.211±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  34
• 可旋转键数：
  9
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  94.2
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  3-isobutyl 5-methyl 1,4-dihydro-2,6-dimethyl-4-(4-pyridyl)-3,5-pyridinedicarboxylate 、 氯甲酸苯酯 在 sodium tetrahydroborate 作用下， 生成 3-O-methyl 5-O-(2-methylpropyl) 2,6-dimethyl-4-(1-phenoxycarbonyl-2H-pyridin-4-yl)-1,4-dihydropyridine-3,5-dicarboxylate
  参考文献：
  名称：

  Synthesis and calcium channel antagonist activity of dialkyl 4-(dihydropyridinyl)-1,4-dihydro-2,6-dimethyl-3,5-pyridinedicarboxylates

  摘要：

  The sodium borohydride reduction of 3,5-disubstituted 1,4-dihydro-2,6-dimethyl-4-(pyridinyl)pyridines 2 and 5 in the presence of methyl, phenyl, or tert-butyl chloroformate afforded the respective 4-(dihydropyridinyl)-1,4-dihydropyridines 4 and 6 in good yield. Products 4 comprised a mixture of the 1,2- and 1,6-dihydropyridinyl regioisomers 4a and 4b where 4a was always the predominant regioisomer. Compounds possessing a 4-[dihydro-1-(phenoxycarbonyl)-3-pyridinyl] substituent, such as 26, were also a mixture of two regioisomers 26a and 26b, and each regioisomer existed as a mixture of two rotamers in Me2SO-d6 at 25 degrees C (26a', 26a'', and 26b', 26b'') due to restricted rotation about the nitrogen-to-carbonyl carbamate bond. The calcium antagonist activities for 4 and 6 were determined by using the muscarinic receptor-mediated Ca2+-dependent contraction of guinea pig ileal longitudinal smooth muscle. The relative order of activities for the 4-(dihydropyridinyl) analogues was 4-(dihydro-3-pyridinyl) greater than 4-(dihydro-4-pyridinyl). Increasing the size of the C-3(5) alkyl ester substituents increased activity. Compounds having nonidentical ester substituents were more active than those having identical ester substituents. Replacement of the C-3 and/or C-5 ester substituents by a cyano substituent(s) decreased activity significantly. An approximate 1:1 correlation between the IC50 value for inhibition of [3H]nitrendipine binding and inhibition of the tonic component of the muscarinic-induced contractile response was observed. The test results suggest that a 4-(dihydropyridinyl) substituent is bioisosteric with a 4-(nitrophenyl) substituent on a 1,4-dihydropyridine ring where m- and p-nitrophenyl are bioisosteric with the 4-[1,2(1,6)-dihydro-3-pyridinyl] 4 and 4-(1,2-dihydro-4-pyridinyl) 6 isomers, respectively.

  DOI：

  10.1021/jm00387a010

文献信息

• DAGNINO L.; LI-KWONG-KEN MOY CH.; WYNN HLA; WOLOWYK M. W.; TRIGGLE CH. R.+, J. MED. CHEM., 30,(1987) N 4, 640-646
  作者：DAGNINO L.、 LI-KWONG-KEN MOY CH.、 WYNN HLA、 WOLOWYK M. W.、 TRIGGLE CH. R.+

  DOI：——

  日期：——
• Synthesis and calcium channel antagonist activity of dialkyl 4-(dihydropyridinyl)-1,4-dihydro-2,6-dimethyl-3,5-pyridinedicarboxylates
  作者：Lina Dagnino、Moy Cheong Li-Kwong-Ken、Hla Wynn、Michael W. Wolowyk、Christopher R. Triggle、Edward E. Knaus

  DOI：10.1021/jm00387a010

  日期：1987.4

  The sodium borohydride reduction of 3,5-disubstituted 1,4-dihydro-2,6-dimethyl-4-(pyridinyl)pyridines 2 and 5 in the presence of methyl, phenyl, or tert-butyl chloroformate afforded the respective 4-(dihydropyridinyl)-1,4-dihydropyridines 4 and 6 in good yield. Products 4 comprised a mixture of the 1,2- and 1,6-dihydropyridinyl regioisomers 4a and 4b where 4a was always the predominant regioisomer. Compounds possessing a 4-[dihydro-1-(phenoxycarbonyl)-3-pyridinyl] substituent, such as 26, were also a mixture of two regioisomers 26a and 26b, and each regioisomer existed as a mixture of two rotamers in Me2SO-d6 at 25 degrees C (26a', 26a'', and 26b', 26b'') due to restricted rotation about the nitrogen-to-carbonyl carbamate bond. The calcium antagonist activities for 4 and 6 were determined by using the muscarinic receptor-mediated Ca2+-dependent contraction of guinea pig ileal longitudinal smooth muscle. The relative order of activities for the 4-(dihydropyridinyl) analogues was 4-(dihydro-3-pyridinyl) greater than 4-(dihydro-4-pyridinyl). Increasing the size of the C-3(5) alkyl ester substituents increased activity. Compounds having nonidentical ester substituents were more active than those having identical ester substituents. Replacement of the C-3 and/or C-5 ester substituents by a cyano substituent(s) decreased activity significantly. An approximate 1:1 correlation between the IC50 value for inhibition of [3H]nitrendipine binding and inhibition of the tonic component of the muscarinic-induced contractile response was observed. The test results suggest that a 4-(dihydropyridinyl) substituent is bioisosteric with a 4-(nitrophenyl) substituent on a 1,4-dihydropyridine ring where m- and p-nitrophenyl are bioisosteric with the 4-[1,2(1,6)-dihydro-3-pyridinyl] 4 and 4-(1,2-dihydro-4-pyridinyl) 6 isomers, respectively.