N',N'-dimethyl-N-[3-[[(2R)-oxolan-2-yl]methyl]-5-(trifluoromethyl)triazolo[4,5-d]pyrimidin-7-yl]ethane-1,2-diamine | 1397685-92-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 三唑并嘧啶类
• 英文名称: N',N'-dimethyl-N-[3-[[(2R)-oxolan-2-yl]methyl]-5-(trifluoromethyl)triazolo[4,5-d]pyrimidin-7-yl]ethane-1,2-diamine
• CAS: 1397685-92-5
• 化学式: C₁₄H₂₀F₃N₇O
• 分子量: 359.354
• InChiKey: ZREFLSZDTFZOSF-SECBINFHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  25
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.71
• 拓扑面积：
  81
• 氢给体数：
  1
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  2-三氟甲基-4,6-二羟基嘧啶 在 硝酸 、 铁粉 、 溶剂黄146 、 N,N-二异丙基乙胺 、 N,N-二乙基苯胺 、 sodium nitrite 、 三氯氧磷 作用下， 以 1,4-二氧六环 、 N-甲基吡咯烷酮 、 二氯甲烷 、 水 为溶剂， 反应 29.5h， 生成 N',N'-dimethyl-N-[3-[[(2R)-oxolan-2-yl]methyl]-5-(trifluoromethyl)triazolo[4,5-d]pyrimidin-7-yl]ethane-1,2-diamine
  参考文献：
  名称：

  Discovery of triazolopyrimidine-based PDE8B inhibitors: Exceptionally ligand-efficient and lipophilic ligand-efficient compounds for the treatment of diabetes

  摘要：

  PDE8B is a cAMP-specific isoform of the broader class of phosphodiesterases (PDEs). As no selective PDE8B inhibitors had been reported, a high throughput screen was run with the goal of identifying selective tools for exploring the potential therapeutic utility of PDE8B inhibition. Of the numerous hits, one was particularly attractive since it was amenable to rapid deconstruction leading to inhibitors with very high ligand efficiency (LE) and lipophilic ligand efficiency (LLE). These triazolopyrimidines were optimized for potency, selectivity and ADME properties ultimately leading to compound 42. This compound was highly potent and selective with good bioavailability and advanced into pre-clinical development. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.06.079

文献信息

• Discovery of triazolopyrimidine-based PDE8B inhibitors: Exceptionally ligand-efficient and lipophilic ligand-efficient compounds for the treatment of diabetes
  作者：Michael P. DeNinno、Stephen W. Wright、John B. Etienne、Thanh V. Olson、Benjamin N. Rocke、Jeffrey W. Corbett、Daniel W. Kung、Kenneth J. DiRico、Kim M. Andrews、Michele L. Millham、Janice C. Parker、William Esler、Maria van Volkenburg、David D. Boyer、Karen L. Houseknecht、Shawn D. Doran

  DOI：10.1016/j.bmcl.2012.06.079

  日期：2012.9

  PDE8B is a cAMP-specific isoform of the broader class of phosphodiesterases (PDEs). As no selective PDE8B inhibitors had been reported, a high throughput screen was run with the goal of identifying selective tools for exploring the potential therapeutic utility of PDE8B inhibition. Of the numerous hits, one was particularly attractive since it was amenable to rapid deconstruction leading to inhibitors with very high ligand efficiency (LE) and lipophilic ligand efficiency (LLE). These triazolopyrimidines were optimized for potency, selectivity and ADME properties ultimately leading to compound 42. This compound was highly potent and selective with good bioavailability and advanced into pre-clinical development. (C) 2012 Elsevier Ltd. All rights reserved.