N-(5,6-dihydrothiazolo[2,3-c][1,2,4]triazol-3-yl)-3-(2,6-dimethylphenyl)propionamide | 1449767-08-1

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: N-(5,6-dihydrothiazolo[2,3-c][1,2,4]triazol-3-yl)-3-(2,6-dimethylphenyl)propionamide
• 英文别名: N-(5,6-dihydro-[1,3]thiazolo[2,3-c][1,2,4]triazol-3-yl)-3-(2,6-dimethylphenyl)propanamide
• CAS: 1449767-08-1
• 化学式: C₁₅H₁₈N₄OS
• 分子量: 302.4
• InChiKey: LYJMTDMQIGWSDV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  21
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  85.1
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  3-amino-5,6-dihydro-thiazolo[2,3-c][1,2,4]triazole hydrobromide 、 3-(2,6-二甲基苯基)丙酸 在 4-二甲氨基吡啶 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 16.0h， 以64%的产率得到N-(5,6-dihydrothiazolo[2,3-c][1,2,4]triazol-3-yl)-3-(2,6-dimethylphenyl)propionamide
  参考文献：
  名称：

  Structure–Efficiency Relationship of [1,2,4]Triazol-3-ylamines as Novel Nicotinamide Isosteres that Inhibit Tankyrases

  摘要：

  Tankyrases 1 and 2 are members of the poly(ADP-ribose) polymerase (PARP) family of enzymes that modulate Wnt pathway signaling. While amide- and lactam-based nicotinamide mimetics that inhibit tankyrase activity, such as XAV939, are well-known, herein we report the discovery and evaluation of a novel nicotinamide isostere that demonstrates selectivity over,other PARP family members. We demonstrate the utilization of lipophilic efficiency-based structure efficiency relationships (SER) to rapidly drive the evaluation of this series. These efforts led to a series of selective, cell-active compounds with solubility, physicochemical, and in vitro properties suitable for further optimization.

  DOI：

  10.1021/jm400826j

文献信息

• Structure–Efficiency Relationship of [1,2,4]Triazol-3-ylamines as Novel Nicotinamide Isosteres that Inhibit Tankyrases
  作者：Michael D. Shultz、Dyuti Majumdar、Donovan N. Chin、Pascal D. Fortin、Yun Feng、Ty Gould、Christina A. Kirby、Travis Stams、Nigel J. Waters、Wenlin Shao

  DOI：10.1021/jm400826j

  日期：2013.9.12

  Tankyrases 1 and 2 are members of the poly(ADP-ribose) polymerase (PARP) family of enzymes that modulate Wnt pathway signaling. While amide- and lactam-based nicotinamide mimetics that inhibit tankyrase activity, such as XAV939, are well-known, herein we report the discovery and evaluation of a novel nicotinamide isostere that demonstrates selectivity over,other PARP family members. We demonstrate the utilization of lipophilic efficiency-based structure efficiency relationships (SER) to rapidly drive the evaluation of this series. These efforts led to a series of selective, cell-active compounds with solubility, physicochemical, and in vitro properties suitable for further optimization.