Tert-butyl 3-[(4-cyano-2,5-difluorophenyl)carbamoyl]-1-oxa-2,8-diazaspiro[4.5]dec-2-ene-8-carboxylate | 1415730-95-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 氮杂螺癸烷衍生物
• 英文名称: Tert-butyl 3-[(4-cyano-2,5-difluorophenyl)carbamoyl]-1-oxa-2,8-diazaspiro[4.5]dec-2-ene-8-carboxylate
• 英文别名: tert-butyl 3-[(4-cyano-2,5-difluorophenyl)carbamoyl]-1-oxa-2,8-diazaspiro[4.5]dec-2-ene-8-carboxylate
• CAS: 1415730-95-8
• 化学式: C₂₀H₂₂F₂N₄O₄
• 分子量: 420.416
• InChiKey: VLAWYUXSYNOAQE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  30
• 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：
  104
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  8-(叔丁氧基羰基)-1-噁-2,8-二氮杂螺[4.5]-2-癸烯-3-羧酸 、 4-氨基-2,5-二氟苯甲腈 在 N,N,N',N'-tetramethylchloroformamidinium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 为溶剂， 反应 12.75h， 以33%的产率得到Tert-butyl 3-[(4-cyano-2,5-difluorophenyl)carbamoyl]-1-oxa-2,8-diazaspiro[4.5]dec-2-ene-8-carboxylate
  参考文献：
  名称：

  Identification of New Potent GPR119 Agonists by Combining Virtual Screening and Combinatorial Chemistry

  摘要：

  Virtual screening in a huge collection of virtual combinatorial libraries has led to the identification of two new structural classes of GPR119 agonists with submicromolar in vitro potencies. Herein, we describe the virtual screening process involving feature trees fragment space searches followed by a 3D postprocessing step. The in silico findings were then filtered and prioritized, and finally, combinatorial libraries of target molecules were synthesized. Furthermore the so-called "activity-anchor principle" is introduced as an element to increase the chance to generate true hits. An activity anchor is a structural element expected to provide key contributions to a certain biological activity. Application of this technique has led to the discovery of two new GPR119-agonist hit series, one of which was further optimized to progress as a novel lead class.

  DOI：

  10.1021/jm301549a

文献信息

• Identification of New Potent GPR119 Agonists by Combining Virtual Screening and Combinatorial Chemistry
  作者：Bernd Wellenzohn、Uta Lessel、Andreas Beller、Timo Isambert、Christoph Hoenke、Bernd Nosse

  DOI：10.1021/jm301549a

  日期：2012.12.27

  Virtual screening in a huge collection of virtual combinatorial libraries has led to the identification of two new structural classes of GPR119 agonists with submicromolar in vitro potencies. Herein, we describe the virtual screening process involving feature trees fragment space searches followed by a 3D postprocessing step. The in silico findings were then filtered and prioritized, and finally, combinatorial libraries of target molecules were synthesized. Furthermore the so-called "activity-anchor principle" is introduced as an element to increase the chance to generate true hits. An activity anchor is a structural element expected to provide key contributions to a certain biological activity. Application of this technique has led to the discovery of two new GPR119-agonist hit series, one of which was further optimized to progress as a novel lead class.