1,4-dihydro-2,6-dimethyl-4-(3'-methylthiophen-2'-yl)pyridine-3,5-dicarboxylic acid diallyl ester

• 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: 1,4-dihydro-2,6-dimethyl-4-(3'-methylthiophen-2'-yl)pyridine-3,5-dicarboxylic acid diallyl ester
• 英文别名: Bis(prop-2-enyl) 2,6-dimethyl-4-(3-methylthiophen-2-yl)-1,4-dihydropyridine-3,5-dicarboxylate
• 化学式: C₂₀H₂₃NO₄S
• 分子量: 373.473
• InChiKey: RRIXMDDCPQUWIO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  26
• 可旋转键数：
  9
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  92.9
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  3-甲基噻吩醛 、 乙酰乙酸烯丙酯 在 氨 作用下， 以 甲醇 为溶剂， 以75%的产率得到1,4-dihydro-2,6-dimethyl-4-(3'-methylthiophen-2'-yl)pyridine-3,5-dicarboxylic acid diallyl ester
  参考文献：
  名称：

  Synthesis of 4-thiophen-2′-yl-1,4-dihydropyridines as potentiators of the CFTR chloride channel

  摘要：

  The gating of the CFTR chloride channel is altered by a group of mutations that cause cystic fibrosis. This gating defect may be corrected by small molecules called potentiators. Some 1,4-dihydropyridine (DHP) derivatives, bearing a thiophen-2-yl and a furanyl ring at the 4-position of the nucleus, were prepared and tested as CFTR potentiators. In particular, we evaluated the ability of novel DHPs to enhance the activity of the rescued Delta F508-CFTR as measured with a functional assay based on the halide-sensitive yellow fluorescent protein. Most DHPs showed an effect comparable to or better than that of the reference compound genistein. The potency was instead significantly improved, with some compounds, such as 3g, 3h, 3n, 4a, 4b, and 4d, having a half effective concentration in the submicromolar range. CoMFA analysis gave helpful suggestions to improve the activity of DHPs. (c) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2009.10.028

文献信息

• Synthesis and activities of a thienyl dihydropyridine series on intracellular calcium in a rat pituitary cell line (GH3/B6)
  作者：M Varache-Lembège、A Nuhrich、V Zemb、G Devaux、P Vacher、AM Vacher、B Dufy

  DOI：10.1016/0223-5234(96)89551-1

  日期：1996.1

  The synthesis of a thienyl dihydropyridine series according to the Hantzsch method is described. The influence of these derivatives on intracellular calcium ([Ca2+]i) in GH3 cells was evaluated in vitro using spectrofluorimetry with indol as Ca2+ fluorescent probe. We compared their effects on [Ca2+]i and hormone release with those of nifedipine. The most active tested compounds on [Ca2+]i were those methylated on the 3-position of the thienyl ring (activity was about 75% of nifedipine). Interestingly, the most efficient compounds on [Ca2+]i were also the most efficient on hormone release.
• Synthesis of 4-thiophen-2′-yl-1,4-dihydropyridines as potentiators of the CFTR chloride channel
  作者：Francesca Cateni、Marina Zacchigna、Nicoletta Pedemonte、Luis J.V. Galietta、Marco T. Mazzei、Paola Fossa、Michele Giampieri、Mauro Mazzei

  DOI：10.1016/j.bmc.2009.10.028

  日期：2009.12

  The gating of the CFTR chloride channel is altered by a group of mutations that cause cystic fibrosis. This gating defect may be corrected by small molecules called potentiators. Some 1,4-dihydropyridine (DHP) derivatives, bearing a thiophen-2-yl and a furanyl ring at the 4-position of the nucleus, were prepared and tested as CFTR potentiators. In particular, we evaluated the ability of novel DHPs to enhance the activity of the rescued Delta F508-CFTR as measured with a functional assay based on the halide-sensitive yellow fluorescent protein. Most DHPs showed an effect comparable to or better than that of the reference compound genistein. The potency was instead significantly improved, with some compounds, such as 3g, 3h, 3n, 4a, 4b, and 4d, having a half effective concentration in the submicromolar range. CoMFA analysis gave helpful suggestions to improve the activity of DHPs. (c) 2009 Elsevier Ltd. All rights reserved.