4-methoxy-2,3,6-trimethyl-N-((1,3,5-trimethyl-1H-pyrazol-4-yl)methyl)benzenesulfonamide | 1215009-01-0

• 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-methoxy-2,3,6-trimethyl-N-((1,3,5-trimethyl-1H-pyrazol-4-yl)methyl)benzenesulfonamide
• 英文别名: US9156811, Ddd71296；4-methoxy-2,3,6-trimethyl-N-[(1,3,5-trimethylpyrazol-4-yl)methyl]benzenesulfonamide
• CAS: 1215009-01-0
• 化学式: C₁₇H₂₅N₃O₃S
• 分子量: 351.47
• InChiKey: CTBXHFIQWUZMLK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  24
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  81.6
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  1,3,5-三甲基-吡唑-4-甲胺 、 4-甲氧基-2,3,6-三甲基苯磺酰氯 在 吡啶 作用下， 以89%的产率得到4-methoxy-2,3,6-trimethyl-N-((1,3,5-trimethyl-1H-pyrazol-4-yl)methyl)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：US20110312921A1

  公开（公告）日：2011-12-22

  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-肉豆蔻酰转移酶抑制剂的用途。
• N-MYRISTOYL TRANSFERASE INHIBITORS
  申请人：Brand Stephen

  公开号：US20160060224A1

  公开（公告）日：2016-03-03

  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-杂环磺酰胺化合物，特别是吡唑磺酰胺化合物，及其作为N-肉豆蔻酰转移酶抑制剂的用途。
• US9156811B2
  申请人：——

  公开号：US9156811B2

  公开（公告）日：2015-10-13
• US9828346B2
  申请人：——

  公开号：US9828346B2

  公开（公告）日：2017-11-28
• Discovery of a Novel Class of Orally Active Trypanocidal <i>N</i>-Myristoyltransferase Inhibitors
  作者：Stephen Brand、Laura A. T. Cleghorn、Stuart P. McElroy、David A. Robinson、Victoria C. Smith、Irene Hallyburton、Justin R. Harrison、Neil R. Norcross、Daniel Spinks、Tracy Bayliss、Suzanne Norval、Laste Stojanovski、Leah S. Torrie、Julie A. Frearson、Ruth Brenk、Alan H. Fairlamb、Michael A. J. Ferguson、Kevin D. Read、Paul G. Wyatt、Ian H. Gilbert

  DOI：10.1021/jm201091t

  日期：2012.1.12

  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.