8-(2'-aminobiphenyl-4-ylmethoxy)-3,5,10-trioxatricyclo[6.2.1.0^2,6]undecane-4,9-dione | 859224-79-6

• 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: 8-(2'-aminobiphenyl-4-ylmethoxy)-3,5,10-trioxatricyclo[6.2.1.0^2,6]undecane-4,9-dione
• 英文别名: (1R,2S,6R,8R)-8-[[4-(2-aminophenyl)phenyl]methoxy]-3,5,10-trioxatricyclo[6.2.1.02,6]undecane-4,9-dione
• CAS: 859224-79-6
• 化学式: C₂₁H₁₉NO₆
• 分子量: 381.385
• InChiKey: KMPQRTDLVKRAMX-DCXXXQMHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  28
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  97.1
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  8-(2'-aminobiphenyl-4-ylmethoxy)-3,5,10-trioxatricyclo[6.2.1.0^2,6]undecane-4,9-dione 在 lithium hydroxide 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 乙腈 为溶剂， 反应 48.0h， 生成 (3R,5R)-3,4,5-trihydroxy-1-{2'-[(5-methyl-2-phenyl-2H-[1,2,3]triazole-4-carbonyl)amino]biphenyl-4-ylmethoxy}cyclohexanecarboxylic acid
  参考文献：
  名称：

  Quinic Acid Derivatives as Sialyl Lewis^x-Mimicking Selectin Inhibitors:  Design, Synthesis, and Crystal Structure in Complex with E-Selectin

  摘要：

  A search for noncarbohydrate sLe(x) mimics led to the development of quinic acid derivatives as selectin inhibitors. At Wyeth we solved the first cocrystal structure of a small molecule, quinic acid, with E-selectin. In the cocomplex two hydroxyls of quinic acid mimic the calcium-bound fucose of the tetrasaccharide sLe(x). The X-ray structure, together with structure based computational methods, was used to design quinic acid based libraries that were synthesized and evaluated for their ability to block the interaction of sLex with P-selectin. A large number of analogues were prepared using solution-phase parallel synthesis. Selected compounds showed decrease in leukocyte rolling in the IVM mouse model. Compound 2 inhibited neutrophil influx in the murine TIP model and demonstrated good plasma exposure.

  DOI：

  10.1021/jm050049l
• 作为产物：
  描述：

  右旋奎宁酸 在 吡啶 、 sodium hydride 、 对甲苯磺酸 、 tin(ll) chloride 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 、 苯 为溶剂， 反应 29.5h， 生成 8-(2'-aminobiphenyl-4-ylmethoxy)-3,5,10-trioxatricyclo[6.2.1.0^2,6]undecane-4,9-dione
  参考文献：
  名称：

  Quinic Acid Derivatives as Sialyl Lewis^x-Mimicking Selectin Inhibitors:  Design, Synthesis, and Crystal Structure in Complex with E-Selectin

  摘要：

  A search for noncarbohydrate sLe(x) mimics led to the development of quinic acid derivatives as selectin inhibitors. At Wyeth we solved the first cocrystal structure of a small molecule, quinic acid, with E-selectin. In the cocomplex two hydroxyls of quinic acid mimic the calcium-bound fucose of the tetrasaccharide sLe(x). The X-ray structure, together with structure based computational methods, was used to design quinic acid based libraries that were synthesized and evaluated for their ability to block the interaction of sLex with P-selectin. A large number of analogues were prepared using solution-phase parallel synthesis. Selected compounds showed decrease in leukocyte rolling in the IVM mouse model. Compound 2 inhibited neutrophil influx in the murine TIP model and demonstrated good plasma exposure.

  DOI：

  10.1021/jm050049l

文献信息

• Quinic Acid Derivatives as Sialyl Lewis^x-Mimicking Selectin Inhibitors:  Design, Synthesis, and Crystal Structure in Complex with E-Selectin
  作者：Neelu Kaila、William S. Somers、Bert E. Thomas、Paresh Thakker、Kristin Janz、Silvano DeBernardo、Steve Tam、William J. Moore、Ruiyang Yang、Wojciech Wrona、Patricia W. Bedard、Deidre Crommie、James C. Keith,、Desiree H. H. Tsao、Juan C. Alvarez、Heyu Ni、Erik Marchese、John T. Patton、John L. Magnani、Raymond T. Camphausen

  DOI：10.1021/jm050049l

  日期：2005.6.1

  A search for noncarbohydrate sLe(x) mimics led to the development of quinic acid derivatives as selectin inhibitors. At Wyeth we solved the first cocrystal structure of a small molecule, quinic acid, with E-selectin. In the cocomplex two hydroxyls of quinic acid mimic the calcium-bound fucose of the tetrasaccharide sLe(x). The X-ray structure, together with structure based computational methods, was used to design quinic acid based libraries that were synthesized and evaluated for their ability to block the interaction of sLex with P-selectin. A large number of analogues were prepared using solution-phase parallel synthesis. Selected compounds showed decrease in leukocyte rolling in the IVM mouse model. Compound 2 inhibited neutrophil influx in the murine TIP model and demonstrated good plasma exposure.