3-(3-(4,6-bis(4-chlorophenyl)pyrimidin-2-ylamino)phenoxy)propanoic acid

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: 3-(3-(4,6-bis(4-chlorophenyl)pyrimidin-2-ylamino)phenoxy)propanoic acid
• 英文别名: 3-[3-[[4,6-Bis(4-chlorophenyl)pyrimidin-2-yl]amino]phenoxy]propanoic acid；3-[3-[[4,6-bis(4-chlorophenyl)pyrimidin-2-yl]amino]phenoxy]propanoic acid
• 化学式: C₂₅H₁₉Cl₂N₃O₃
• 分子量: 480.35
• InChiKey: KAKOBHZFNTVNCR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.1
• 重原子数：
  33
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  84.3
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  3-(3-(4,6-bis(4-chlorophenyl)pyrimidin-2-ylamino)phenoxy)propanoic acid 、 甲氧基胺盐酸盐 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43%的产率得到3-(3-(4,6-bis(4-chlorophenyl)pyrimidin-2-ylamino)-phenoxy)-N-methoxypropanamide
  参考文献：
  名称：

  Fine tuning of 4,6-bisphenyl-2-(3-alkoxyanilino)pyrimidine focusing on the activity-sensitive aminoalkoxy moiety for a therapeutically useful inhibitor of receptor for advanced glycation end products (RAGE)

  摘要：

  Through the fine tuning of the activity-sensitive aminoalkoxy moiety of 4,6-bisphenyl-2-(3-alkoxyanilino)pyrimidine as a novel inhibitor of the receptor for advanced glycation end products (RAGE), the tertiary amine was elucidated as an essential part associated with RAGE inhibition. On the basis of this finding, a 3-(N,N-dimethylamino)pyrrolidine analog 12o was identified as a therapeutically useful RAGE inhibitor with improved activity and solubility. Molecular modeling studies predicted that the improved inhibitory activity is induced by additional hydrogen bonds between the nitrogen atom of the pyrrolidine ring and Arg48 and by an interaction between the dimethylamino-substituent of the pyrrolidine moiety and a relatively hydrophobic groove in the RAGE binding site. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2014.12.003
• 作为产物：
  描述：

  3-(3-氨基苯氧基)-1-丙醇 在 chromium(VI) oxide 、 盐酸 、 硫酸 作用下， 以 1,4-二氧六环 、 水 、 丙酮 、 正丁醇 为溶剂， 反应 1.5h， 生成 3-(3-(4,6-bis(4-chlorophenyl)pyrimidin-2-ylamino)phenoxy)propanoic acid
  参考文献：
  名称：

  Fine tuning of 4,6-bisphenyl-2-(3-alkoxyanilino)pyrimidine focusing on the activity-sensitive aminoalkoxy moiety for a therapeutically useful inhibitor of receptor for advanced glycation end products (RAGE)

  摘要：

  Through the fine tuning of the activity-sensitive aminoalkoxy moiety of 4,6-bisphenyl-2-(3-alkoxyanilino)pyrimidine as a novel inhibitor of the receptor for advanced glycation end products (RAGE), the tertiary amine was elucidated as an essential part associated with RAGE inhibition. On the basis of this finding, a 3-(N,N-dimethylamino)pyrrolidine analog 12o was identified as a therapeutically useful RAGE inhibitor with improved activity and solubility. Molecular modeling studies predicted that the improved inhibitory activity is induced by additional hydrogen bonds between the nitrogen atom of the pyrrolidine ring and Arg48 and by an interaction between the dimethylamino-substituent of the pyrrolidine moiety and a relatively hydrophobic groove in the RAGE binding site. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2014.12.003

文献信息

• Fine tuning of 4,6-bisphenyl-2-(3-alkoxyanilino)pyrimidine focusing on the activity-sensitive aminoalkoxy moiety for a therapeutically useful inhibitor of receptor for advanced glycation end products (RAGE)
  作者：Young Taek Han、Kyeojin Kim、Dohyun Son、Hongchan An、Hee Kim、Jeeyeon Lee、Hyun-Ju Park、Jeewoo Lee、Young-Ger Suh

  DOI：10.1016/j.bmc.2014.12.003

  日期：2015.2

  Through the fine tuning of the activity-sensitive aminoalkoxy moiety of 4,6-bisphenyl-2-(3-alkoxyanilino)pyrimidine as a novel inhibitor of the receptor for advanced glycation end products (RAGE), the tertiary amine was elucidated as an essential part associated with RAGE inhibition. On the basis of this finding, a 3-(N,N-dimethylamino)pyrrolidine analog 12o was identified as a therapeutically useful RAGE inhibitor with improved activity and solubility. Molecular modeling studies predicted that the improved inhibitory activity is induced by additional hydrogen bonds between the nitrogen atom of the pyrrolidine ring and Arg48 and by an interaction between the dimethylamino-substituent of the pyrrolidine moiety and a relatively hydrophobic groove in the RAGE binding site. (C) 2014 Elsevier Ltd. All rights reserved.