2,6-dichloro-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-N-(1,3,5-trimethyl-1H-pyrazol-4-yl)benzenesulfonamide | 1215013-78-7

• 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: 2,6-dichloro-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-N-(1,3,5-trimethyl-1H-pyrazol-4-yl)benzenesulfonamide
• 英文别名: 2,6-dichloro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-N-(1,3,5-trimethylpyrazol-4-yl)benzenesulfonamide
• CAS: 1215013-78-7
• 化学式: C₁₈H₂₄BCl₂N₃O₄S
• 分子量: 460.189
• InChiKey: UKFMLPPTKZGXJW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.44
• 重原子数：
  29
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  90.8
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  2,6-dichloro-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-N-(1,3,5-trimethyl-1H-pyrazol-4-yl)benzenesulfonamide 、 5-溴-1,2,3,4-四氢异喹啉 在 potassium phosphate 、 四(三苯基膦)钯 作用下， 以 水 、 N,N-二甲基甲酰胺 为溶剂， 生成 2,6-dichloro-4-(1,2,3,4-tetrahydroisoquinolin-5-yl)-N-(1,3,5-trimethyl-1H-pyrazol-4-yl)benzenesulfonamide
  参考文献：
  名称：

  Discovery of a Novel Class of Orally Active Trypanocidal N-Myristoyltransferase Inhibitors

  摘要：

  N-Myristoyltransferase (NMT) represents a promising drug target for human African trypanosomiasis (HAT), which is caused by the parasitic protozoa Trypanosoma brucei. We report the optimization of a high throughput screening hit (1) to give a lead molecule DDD85646 (63), which has potent activity against the enzyme (IC50 = 2 nM) and T. brucei (EC50 = 2 nM) in culture. The compound has good oral pharmacokinetics and cures rodent models of peripheral HAT infection. This compound provides an excellent tool for validation of T. brucei NMT as a drug target for HAT as well as a valuable lead for further optimization.

  DOI：

  10.1021/jm201091t
• 作为产物：
  描述：

  4-溴-2,6-二氯苯磺酰氯 在 吡啶 、 potassium phosphate 、 四(三苯基膦)钯 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 生成 2,6-dichloro-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-N-(1,3,5-trimethyl-1H-pyrazol-4-yl)benzenesulfonamide
  参考文献：
  名称：

  Discovery of a Novel Class of Orally Active Trypanocidal N-Myristoyltransferase Inhibitors

  摘要：

  N-Myristoyltransferase (NMT) represents a promising drug target for human African trypanosomiasis (HAT), which is caused by the parasitic protozoa Trypanosoma brucei. We report the optimization of a high throughput screening hit (1) to give a lead molecule DDD85646 (63), which has potent activity against the enzyme (IC50 = 2 nM) and T. brucei (EC50 = 2 nM) in culture. The compound has good oral pharmacokinetics and cures rodent models of peripheral HAT infection. This compound provides an excellent tool for validation of T. brucei NMT as a drug target for HAT as well as a valuable lead for further optimization.

  DOI：

  10.1021/jm201091t

文献信息

• N-myristoyl transferase inhibitors
  申请人：Brand Stephen

  公开号：US09156811B2

  公开（公告）日：2015-10-13

  The present invention relates to N-heterocyclic sulphonamide compounds, in particular pyrazole sulphonamide compounds, and their use as N-myristoyl transferase inhibitors.

  本发明涉及N-杂环磺胺化合物，特别是吡唑磺胺化合物，以及它们作为N-肟酰基转移酶抑制剂的用途。