N-(3-morpholinopropyl)-1-[4-(aminosulfonyl)phenyl]-2-methyl-5-(2-naphthyl)-1H-pyrrole-3-carboxamide | 1258267-87-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯
• 英文名称: N-(3-morpholinopropyl)-1-[4-(aminosulfonyl)phenyl]-2-methyl-5-(2-naphthyl)-1H-pyrrole-3-carboxamide
• 英文别名: 2-methyl-N-(3-morpholin-4-ylpropyl)-5-naphthalen-2-yl-1-(4-sulfamoylphenyl)pyrrole-3-carboxamide
• CAS: 1258267-87-6
• 化学式: C₂₉H₃₂N₄O₄S
• 分子量: 532.663
• InChiKey: RNVCNJNMDXFPJW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  38
• 可旋转键数：
  8
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  115
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  N-(3-氨丙基)吗啉 、 N3-[3-(4-Methylpiperazino)propyl]-1-[4-(aminosulfonyl)phenyl]-2-methyl-5-(4-biphenylyl)-1H-3-pyrrolecarboxamide 在 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 8.0h， 生成 N-(3-morpholinopropyl)-1-[4-(aminosulfonyl)phenyl]-2-methyl-5-(2-naphthyl)-1H-pyrrole-3-carboxamide
  参考文献：
  名称：

  Design, solid-phase synthesis, and biological evaluation of novel 1,5-diarylpyrrole-3-carboxamides as carbonic anhydrase IX inhibitors

  摘要：

  Following previous studies we herein report the synthesis and the pharmacological evaluation of a new class of human carbonic anhydrase (hCA) inhibitors, 1,5-diarylpyrrole-3-carboxamides prepared by a solid-phase strategy involving a PS(HOBt) resin. A molecular modeling study was conducted in order to simulate the binding mode of this new family of enzyme inhibitors within the active site of hCA IX. This study revealed that the 3-position of the pyrrole was opened to the solvent, so we introduced an amino side-chain, protonated at physiological pH both to enhance the aqueous solubility and to decrease the cell membrane penetration. This strategy consisted of preparing membrane-impermeant inhibitors that may selectively target the tumor-associated hCA IX. Physico-chemical characterizations including aqueous solubility and lipophilic parameters are described. Pharmacological studies revealed high hCA IX inhibitory potency in the nanomolar range. Some compounds are selective for hCA IX displaying hCA I/hCA IX and hCA II/hCA IX ratios higher than 20 and 5, respectively. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2010.09.007

文献信息

• Design, solid-phase synthesis, and biological evaluation of novel 1,5-diarylpyrrole-3-carboxamides as carbonic anhydrase IX inhibitors
  作者：Sébastien Gluszok、Raphaël Frédérick、Catherine Foulon、Frédérique Klupsch、Claudiu T. Supuran、Daniela Vullo、Andrea Scozzafava、Jean-François Goossens、Bernard Masereel、Patrick Depreux、Laurence Goossens

  DOI：10.1016/j.bmc.2010.09.007

  日期：2010.11

  Following previous studies we herein report the synthesis and the pharmacological evaluation of a new class of human carbonic anhydrase (hCA) inhibitors, 1,5-diarylpyrrole-3-carboxamides prepared by a solid-phase strategy involving a PS(HOBt) resin. A molecular modeling study was conducted in order to simulate the binding mode of this new family of enzyme inhibitors within the active site of hCA IX. This study revealed that the 3-position of the pyrrole was opened to the solvent, so we introduced an amino side-chain, protonated at physiological pH both to enhance the aqueous solubility and to decrease the cell membrane penetration. This strategy consisted of preparing membrane-impermeant inhibitors that may selectively target the tumor-associated hCA IX. Physico-chemical characterizations including aqueous solubility and lipophilic parameters are described. Pharmacological studies revealed high hCA IX inhibitory potency in the nanomolar range. Some compounds are selective for hCA IX displaying hCA I/hCA IX and hCA II/hCA IX ratios higher than 20 and 5, respectively. (C) 2010 Elsevier Ltd. All rights reserved.