(R)-N-[1-(4-methoxyphenyl)ethyl]-1H-indole-2-carboxamide

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: (R)-N-[1-(4-methoxyphenyl)ethyl]-1H-indole-2-carboxamide
• 英文别名: N-[(1R)-1-(4-methoxyphenyl)ethyl]-1H-indole-2-carboxamide
• 化学式: C₁₈H₁₈N₂O₂
• 分子量: 294.353
• InChiKey: MXJZPVOAIBCQBO-GFCCVEGCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.67
• 重原子数：
  22.0
• 可旋转键数：
  4.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  54.12
• 氢给体数：
  2.0
• 氢受体数：
  2.0

反应信息

• 作为反应物：
  描述：

  (R)-N-[1-(4-methoxyphenyl)ethyl]-1H-indole-2-carboxamide 在 aluminum (III) chloride 、 lithium aluminium tetrahydride 作用下， 以 四氢呋喃 为溶剂， 反应 20.0h， 以52%的产率得到(R)-N-(1H-indol-2-ylmethyl)-1-(4-methoxyphenyl)ethanamine
  参考文献：
  名称：

  Design and synthesis of calindol derivatives as potent and selective calcium sensing receptor agonists

  摘要：

  We report the first comprehensive structure-activity study of calindol (4, (R)-N-[(1H-indol-2-yl) methyl]1-(1-naphthyl) ethanamine), a positive allosteric modulator, or calcimimetic, of the calcium sensing receptor (CaSR). While replacement of the naphthyl moiety of calindol by other aromatic groups (phenyl, biphenyl) was largely detrimental to calcimimetic activity, incorporation of substituents on the 4, 5 or 7 position of the indole portion of calindol was found to provide either equipotent derivatives compared to calindol (e.g., 4-phenyl, 4-hydroxy, 5-hydroxycalindol 44, 52, 53) or, in the case of 7-nitrocalindol (51), a 6-fold more active calcimimetic displaying an EC50 of 20 nM. Unlike calindol, the more active CaSR calcimimetics were shown not to act as antagonists of the closely related GPRC6A receptor, suggesting a more selective profile for these new analogues. (c) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2015.12.019
• 作为产物：
  描述：

  吲哚-2-羧酸 、 (R)-(+)-1-(4-甲氧基苯)乙胺 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 以62%的产率得到(R)-N-[1-(4-methoxyphenyl)ethyl]-1H-indole-2-carboxamide
  参考文献：
  名称：

  Design and synthesis of calindol derivatives as potent and selective calcium sensing receptor agonists

  摘要：

  We report the first comprehensive structure-activity study of calindol (4, (R)-N-[(1H-indol-2-yl) methyl]1-(1-naphthyl) ethanamine), a positive allosteric modulator, or calcimimetic, of the calcium sensing receptor (CaSR). While replacement of the naphthyl moiety of calindol by other aromatic groups (phenyl, biphenyl) was largely detrimental to calcimimetic activity, incorporation of substituents on the 4, 5 or 7 position of the indole portion of calindol was found to provide either equipotent derivatives compared to calindol (e.g., 4-phenyl, 4-hydroxy, 5-hydroxycalindol 44, 52, 53) or, in the case of 7-nitrocalindol (51), a 6-fold more active calcimimetic displaying an EC50 of 20 nM. Unlike calindol, the more active CaSR calcimimetics were shown not to act as antagonists of the closely related GPRC6A receptor, suggesting a more selective profile for these new analogues. (c) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2015.12.019

文献信息

• Design and synthesis of calindol derivatives as potent and selective calcium sensing receptor agonists
  作者：Lionel Kiefer、Floriane Beaumard、Tatiana Gorojankina、Hélène Faure、Martial Ruat、Robert H. Dodd

  DOI：10.1016/j.bmc.2015.12.019

  日期：2016.2

  We report the first comprehensive structure-activity study of calindol (4, (R)-N-[(1H-indol-2-yl) methyl]1-(1-naphthyl) ethanamine), a positive allosteric modulator, or calcimimetic, of the calcium sensing receptor (CaSR). While replacement of the naphthyl moiety of calindol by other aromatic groups (phenyl, biphenyl) was largely detrimental to calcimimetic activity, incorporation of substituents on the 4, 5 or 7 position of the indole portion of calindol was found to provide either equipotent derivatives compared to calindol (e.g., 4-phenyl, 4-hydroxy, 5-hydroxycalindol 44, 52, 53) or, in the case of 7-nitrocalindol (51), a 6-fold more active calcimimetic displaying an EC50 of 20 nM. Unlike calindol, the more active CaSR calcimimetics were shown not to act as antagonists of the closely related GPRC6A receptor, suggesting a more selective profile for these new analogues. (c) 2015 Elsevier Ltd. All rights reserved.