4-(aminosulfonyl)-N-[2-(3-ethoxyphenyl)ethyl]benzamide | 1372808-79-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 4-(aminosulfonyl)-N-[2-(3-ethoxyphenyl)ethyl]benzamide
• 英文别名: N-[2-(3-ethoxyphenyl)ethyl]-4-sulfamoylbenzamide
• CAS: 1372808-79-1
• 化学式: C₁₇H₂₀N₂O₄S
• 分子量: 348.423
• InChiKey: HUTCTQGBOFUZJI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  24
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  107
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  4-(aminosulfonyl)-N-[2-(3-ethoxyphenyl)ethyl]benzamide 在 sodium tetrahydroborate 、 三氯氧磷 作用下， 以 甲醇 、 甲苯 为溶剂， 反应 7.0h， 生成 4-(6-ethoxy-1,2,3,4-tetrahydroisoquinolin-1-yl)benzenesulfonamide
  参考文献：
  名称：

  Synthesis, Structure–Activity Relationship Studies, and X-ray Crystallographic Analysis of Arylsulfonamides as Potent Carbonic Anhydrase Inhibitors

  摘要：

  A series of arylsulfonamides has been synthesized and investigated for the inhibition of some selected human carbonic anhydrase isoforms. The studied compounds showed significant inhibitory effects in the nanomolar range toward druggable isoforms (hCA VII, hCA IX, and hCA XIV) (K-i values from 4.8 to 61.7 nM), whereas they generally exhibited significant selectivity over hCA I and hCA II, that are ubiquitous and considered off-target isoforms. On the basis of biochemical data, we herein discussed structure-affinity relationships for this series of arylsulfonamides, suggesting a key role for alkoxy substituents in CA inhibition. Furthermore, X-ray crystal structures of complexes of two active inhibitors (1 and 2a) with hCA II allowed us to elucidate the main interactions between the inhibitor and specific amino acid residues within the catalytic site.

  DOI：

  10.1021/jm300112w
• 作为产物：
  描述：

  对羧基苯磺酰胺 、 3-乙氧基苯乙胺 在 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 1.0h， 以65%的产率得到4-(aminosulfonyl)-N-[2-(3-ethoxyphenyl)ethyl]benzamide
  参考文献：
  名称：

  Synthesis, Structure–Activity Relationship Studies, and X-ray Crystallographic Analysis of Arylsulfonamides as Potent Carbonic Anhydrase Inhibitors

  摘要：

  A series of arylsulfonamides has been synthesized and investigated for the inhibition of some selected human carbonic anhydrase isoforms. The studied compounds showed significant inhibitory effects in the nanomolar range toward druggable isoforms (hCA VII, hCA IX, and hCA XIV) (K-i values from 4.8 to 61.7 nM), whereas they generally exhibited significant selectivity over hCA I and hCA II, that are ubiquitous and considered off-target isoforms. On the basis of biochemical data, we herein discussed structure-affinity relationships for this series of arylsulfonamides, suggesting a key role for alkoxy substituents in CA inhibition. Furthermore, X-ray crystal structures of complexes of two active inhibitors (1 and 2a) with hCA II allowed us to elucidate the main interactions between the inhibitor and specific amino acid residues within the catalytic site.

  DOI：

  10.1021/jm300112w

文献信息

• Synthesis, Structure–Activity Relationship Studies, and X-ray Crystallographic Analysis of Arylsulfonamides as Potent Carbonic Anhydrase Inhibitors
  作者：Rosaria Gitto、Francesca M. Damiano、Pavel Mader、Laura De Luca、Stefania Ferro、Claudiu T. Supuran、Daniela Vullo、Jiří Brynda、Pavlína Řezáčová、Alba Chimirri

  DOI：10.1021/jm300112w

  日期：2012.4.26

  A series of arylsulfonamides has been synthesized and investigated for the inhibition of some selected human carbonic anhydrase isoforms. The studied compounds showed significant inhibitory effects in the nanomolar range toward druggable isoforms (hCA VII, hCA IX, and hCA XIV) (K-i values from 4.8 to 61.7 nM), whereas they generally exhibited significant selectivity over hCA I and hCA II, that are ubiquitous and considered off-target isoforms. On the basis of biochemical data, we herein discussed structure-affinity relationships for this series of arylsulfonamides, suggesting a key role for alkoxy substituents in CA inhibition. Furthermore, X-ray crystal structures of complexes of two active inhibitors (1 and 2a) with hCA II allowed us to elucidate the main interactions between the inhibitor and specific amino acid residues within the catalytic site.