6,7-dimethoxy-1-isopropyl-3,4-dihydroisoquinoline-2(1H)-sulfonamide | 1215113-23-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 四氢异喹啉
• 英文名称: 6,7-dimethoxy-1-isopropyl-3,4-dihydroisoquinoline-2(1H)-sulfonamide
• 英文别名: 6,7-dimethoxy-1-propan-2-yl-3,4-dihydro-1H-isoquinoline-2-sulfonamide
• CAS: 1215113-23-7
• 化学式: C₁₄H₂₂N₂O₄S
• 分子量: 314.406
• InChiKey: BTHWOLGXBUFQAB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  21
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  90.2
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  1‐isopropyl‐6,7‐dimethoxy‐1,2,3,4‐tetrahydroisoquinoline 在 磺酰胺 作用下， 以 dimethoxyethane, 1,1- 为溶剂， 90.0 ℃ 、1.38 MPa 条件下， 反应 0.67h， 以44%的产率得到6,7-dimethoxy-1-isopropyl-3,4-dihydroisoquinoline-2(1H)-sulfonamide
  参考文献：
  名称：

  Identification of 3,4-Dihydroisoquinoline-2(1H)-sulfonamides as Potent Carbonic Anhydrase Inhibitors: Synthesis, Biological Evaluation, and Enzyme−Ligand X-ray Studies

  摘要：

  Following previous studies we herein report the exploration of the carbonic anhydrase (CA, EC 4.2.1.1) inhibitory effects and enzyme selectivity of a small class of 1-(cyclo)alkylisoquinolines containing a sulfonamide function considered a key feature for inhibiting CA. The results of enzymatic assays against human (h) CA isoforms, hCA I and hCA II (cytosolic, ubiquitous enzymes), hCA IX (transmembrane, tumor-associated), and hCA XIV (transmembrane), suggested that the presence of C-1 small substituents on isoquinoline scaffold controls both inhibitory potency and selectivity. Some derivatives showed potent hCA IX and hCA. XIV inhibitory effects at nanomolar concentrations as well as low affinity for the ubiquitous hCA II. Moreover, we report the X-ray crystal structure of one of these derivatives in complex with dominant human isoform II, thus confirming the sulfonamide zinc interactions. Finally, the results of docking experiments suggested the hypothetic interactions in the catalytic binding site for the most active and selective hCA IX and hCA XIV inhibitor.

  DOI：

  10.1021/jm9014026

文献信息

• Identification of 3,4-Dihydroisoquinoline-2(1<i>H</i>)-sulfonamides as Potent Carbonic Anhydrase Inhibitors: Synthesis, Biological Evaluation, and Enzyme−Ligand X-ray Studies
  作者：Rosaria Gitto、Stefano Agnello、Stefania Ferro、Laura De Luca、Daniela Vullo、Jiri Brynda、Pavel Mader、Claudiu T. Supuran、Alba Chimirri

  DOI：10.1021/jm9014026

  日期：2010.3.25

  Following previous studies we herein report the exploration of the carbonic anhydrase (CA, EC 4.2.1.1) inhibitory effects and enzyme selectivity of a small class of 1-(cyclo)alkylisoquinolines containing a sulfonamide function considered a key feature for inhibiting CA. The results of enzymatic assays against human (h) CA isoforms, hCA I and hCA II (cytosolic, ubiquitous enzymes), hCA IX (transmembrane, tumor-associated), and hCA XIV (transmembrane), suggested that the presence of C-1 small substituents on isoquinoline scaffold controls both inhibitory potency and selectivity. Some derivatives showed potent hCA IX and hCA. XIV inhibitory effects at nanomolar concentrations as well as low affinity for the ubiquitous hCA II. Moreover, we report the X-ray crystal structure of one of these derivatives in complex with dominant human isoform II, thus confirming the sulfonamide zinc interactions. Finally, the results of docking experiments suggested the hypothetic interactions in the catalytic binding site for the most active and selective hCA IX and hCA XIV inhibitor.