2-(2-(4-(4-chlorophenyl)-5,6-dihydropyridin-1(2H)-yl)ethyl)iso-indoline-1,3-dione | 1553930-00-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异吲哚及其衍生物
• 英文名称: 2-(2-(4-(4-chlorophenyl)-5,6-dihydropyridin-1(2H)-yl)ethyl)iso-indoline-1,3-dione
• 英文别名: N-{2-[4-(4-chlorophenyl)-1,2,3,6-tetrahydropyridin-1-yl]ethyl}phthalimide；2-[2-[4-(4-chlorophenyl)-3,6-dihydro-2H-pyridin-1-yl]ethyl]isoindole-1,3-dione
• CAS: 1553930-00-9
• 化学式: C₂₁H₁₉ClN₂O₂
• 分子量: 366.847
• InChiKey: WIRXLVFKWXZQIL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  26
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  40.6
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-(2-(4-(4-chlorophenyl)-5,6-dihydropyridin-1(2H)-yl)ethyl)iso-indoline-1,3-dione 在 一水合肼 作用下， 以 乙醇 为溶剂， 反应 2.0h， 以92%的产率得到2-(4-(4-chlorophenyl)-5,6-dihydropyridin-1(2H)-yl)ethanamine
  参考文献：
  名称：

  Synthesis and biological evaluation of 1-(isoxazol-5-ylmethylaminoethyl)-4-phenyl tetrahydropyridine and piperidine derivatives as potent T-type calcium channel blockers with antinociceptive effect in a neuropathic pain model

  摘要：

  New tetrahydropyridinyl and piperidinyl ethylamine derivatives were designed with hypothetical mapping on pharmacophore model generated from ligand-based virtual screening. The designed compounds were synthesized, and their inhibitory activities on T-type calcium channel were assayed using FDSS and patch-clamp assay. Among them, compounds 7b and 10b showed potent T-type calcium current blocking activity against Ca(v)3.1 (alpha(1G)) and Ca(v)3.2 (alpha(1H)) channel simultaneously. With hERG and pharmacokinetics studies, compounds 7b and 10b were evaluated for the antinociceptive effect on rat model of neuropathic pain. They were significantly effective in decreasing the pain responses to mechanical and cold allodynia induced by spinal nerve ligation. These results suggest that modulation of alpha(1G) and am subtype T-type calcium channels may provide a promising approach for the treatment of neuropathic pain. (C) 2014 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2013.12.056
• 作为产物：
  描述：

  tert-butyl 4-(4-chlorophenyl)-5,6-dihydropyridine-1(2H)-carboxylate 在 potassium carbonate 、 三氟乙酸 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 9.0h， 生成 2-(2-(4-(4-chlorophenyl)-5,6-dihydropyridin-1(2H)-yl)ethyl)iso-indoline-1,3-dione
  参考文献：
  名称：

  Synthesis and biological evaluation of 1-(isoxazol-5-ylmethylaminoethyl)-4-phenyl tetrahydropyridine and piperidine derivatives as potent T-type calcium channel blockers with antinociceptive effect in a neuropathic pain model

  摘要：

  New tetrahydropyridinyl and piperidinyl ethylamine derivatives were designed with hypothetical mapping on pharmacophore model generated from ligand-based virtual screening. The designed compounds were synthesized, and their inhibitory activities on T-type calcium channel were assayed using FDSS and patch-clamp assay. Among them, compounds 7b and 10b showed potent T-type calcium current blocking activity against Ca(v)3.1 (alpha(1G)) and Ca(v)3.2 (alpha(1H)) channel simultaneously. With hERG and pharmacokinetics studies, compounds 7b and 10b were evaluated for the antinociceptive effect on rat model of neuropathic pain. They were significantly effective in decreasing the pain responses to mechanical and cold allodynia induced by spinal nerve ligation. These results suggest that modulation of alpha(1G) and am subtype T-type calcium channels may provide a promising approach for the treatment of neuropathic pain. (C) 2014 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2013.12.056

文献信息

• Enhancing a CH−π Interaction to Increase the Affinity for 5-HT_1A Receptors
  作者：Jean-François Liégeois、Marc Lespagnard、Elsa Meneses Salas、Floriane Mangin、Jacqueline Scuvée-Moreau、Sébastien Dilly

  DOI：10.1021/ml4004843

  日期：2014.4.10

  An electrostatic interaction related to a favorable position of the distal phenyl ring and a phenylalanine residue in the binding pocket would explain the higher 5-HT1A affinity of a 4-phenyl-1,2,3,6-tetrahydropyridine (THP) analogue compared to the corresponding 4-phenylpiperazine analogue. To explore a possible reinforcement of this interaction to increase the affinity for 5-HT1A receptors, different 4-substituted-phenyl analogues were synthesized and tested. The most important increase of affinity is obtained with two electron-donating methyl groups in positions 3 and 5.