α,α-difluoro-3,4,5-trimethoxyphenylacetic acid | 251909-12-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: α,α-difluoro-3,4,5-trimethoxyphenylacetic acid
• 英文别名: 2,2-difluoro-3,4,5-trimethoxyphenylacetic acid；2,2-difluoro-2-(3,4,5-trimethoxyphenyl)acetic Acid
• CAS: 251909-12-3
• 化学式: C₁₁H₁₂F₂O₅
• 分子量: 262.21
• InChiKey: TZIPEWWHYMLTOX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  18
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  65
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  α,α-difluoro-3,4,5-trimethoxyphenylacetic acid 在 草酰氯 、 N,N-二异丙基乙胺 、 N,N-二甲基甲酰胺 作用下， 以 二氯甲烷 为溶剂， 反应 3.0h， 生成 1-[2,2-difluoro-2-(3,4,5-trimethoxyphenyl)acetyl]piperidine-2-carboxylic acid 4-phenyl-1-(2-pyridin-3-yl-ethyl)butyl ester
  参考文献：
  名称：

  2-Aryl-2,2-difluoroacetamide FKBP12 Ligands:  Synthesis and X-ray Structural Studies

  摘要：

  [GRAPHICS]2-Aryl-2,2-difluoroacetamido-proline and pipecolate esters are high affinity FKBP12 ligands whose rotamase inhibitory activity is comparable to that seen for the corresponding ketoamides. X-ray structural studies suggest that the fluorine atoms participate in discrete interactions with the Phe36 phenyl ring and the Tyr26 hydroxyl group, with the latter resembling a moderate-to-weak hydrogen bond.

  DOI：

  10.1021/ol0166909
• 作为产物：
  描述：

  3',4',5'-三甲氧基苯乙酮 在 吡啶 、 selenium(IV) oxide 作用下， 以 二氯甲烷 为溶剂， 生成 α,α-difluoro-3,4,5-trimethoxyphenylacetic acid
  参考文献：
  名称：

  2-Aryl-2,2-difluoroacetamide FKBP12 Ligands:  Synthesis and X-ray Structural Studies

  摘要：

  [GRAPHICS]2-Aryl-2,2-difluoroacetamido-proline and pipecolate esters are high affinity FKBP12 ligands whose rotamase inhibitory activity is comparable to that seen for the corresponding ketoamides. X-ray structural studies suggest that the fluorine atoms participate in discrete interactions with the Phe36 phenyl ring and the Tyr26 hydroxyl group, with the latter resembling a moderate-to-weak hydrogen bond.

  DOI：

  10.1021/ol0166909

文献信息

• Design, Synthesis, and Biological Activity of Novel Polycyclic Aza-Amide FKBP12 Ligands
  作者：Raymond A. Hudack,、Nancy S. Barta、Chuangxing Guo、Judith Deal、Liming Dong、Lorraine K. Fay、Bradley Caprathe、Arindam Chatterjee、Darin Vanderpool、Christopher Bigge、Richard Showalter、Steve Bender、Corinne E. Augelli-Szafran、Elizabeth Lunney、Xinjun Hou

  DOI：10.1021/jm049161u

  日期：2006.2.1

  Since the discovery that FK-506 promotes neurite outgrowth, considerable attention has been focused on the development of potent nonimmunosuppressive ligands for FK-506 binding proteins (FKBPs). Such neuroimmunophilin agents have been reported to show neuroregenerative activity in a variety of cell and animal models including neurite outgrowth, age-related cognitive decline, Parkinson's disease, peripheral nerve injury, optic nerve degeneration, and diabetic neuropathy. We have designed and synthesized a unique series of tetracyclic aza-amides that have been shown to be potent FKBP12 rotamase inhibitors. The structure-activity relationships established in this study have demonstrated diverse structural modifications that result in potent rotamase inhibitory activity.
• NEUROTROPHIC DIFLUOROAMIDE AGENTS
  申请人：BRISTOL-MYERS SQUIBB COMPANY

  公开号：EP1087763A1

  公开（公告）日：2001-04-04
• EP1087763A4
  申请人：——

  公开号：EP1087763A4

  公开（公告）日：2002-10-31
• NEUROTROPHIC DIAMIDE AND CARBAMATE AGENTS
  申请人：BRISTOL-MYERS SQUIBB COMPANY

  公开号：EP1129070A1

  公开（公告）日：2001-09-05
• EP1129070A4
  申请人：——

  公开号：EP1129070A4

  公开（公告）日：2005-03-02