2-[benzyl-[(2R)-2-[(4-carbamimidoylphenoxy)methyl]-2,3-dihydro-1,4-benzodioxin-6-yl]amino]-2-oxoacetic acid | 1430559-50-4

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: 2-[benzyl-[(2R)-2-[(4-carbamimidoylphenoxy)methyl]-2,3-dihydro-1,4-benzodioxin-6-yl]amino]-2-oxoacetic acid
• CAS: 1430559-50-4
• 化学式: C₂₅H₂₃N₃O₆
• 分子量: 461.474
• InChiKey: CACQVXQRLSNTQI-HXUWFJFHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  34
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.16
• 拓扑面积：
  135
• 氢给体数：
  3
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  4-[[(2R)-6-amino-2,3-dihydro-1,4-benzodioxin-2-yl]methoxy]benzonitrile 在 盐酸 、 sodium tetrahydroborate 、 三乙胺 、 lithium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 二氯甲烷 为溶剂， 反应 64.5h， 生成 2-[benzyl-[(2R)-2-[(4-carbamimidoylphenoxy)methyl]-2,3-dihydro-1,4-benzodioxin-6-yl]amino]-2-oxoacetic acid
  参考文献：
  名称：

  Towards dual antithrombotic compounds – Balancing thrombin inhibitory and fibrinogen GPIIb/IIIa binding inhibitory activities of 2,3-dihydro-1,4-benzodioxine derivatives through regio- and stereoisomerism

  摘要：

  Enantiomers of 2,3-dihydro-1,4-benzodioxine derivatives possessing both thrombin and fibrinogen GPIIb/IIIa binding inhibitory activities were prepared from (R)- and (S)-glycidol as potential dual antithrombotic compounds. The influence of chirality and substitution pattern on thrombin inhibition and on inhibition of fibrinogen binding to GPIIb/IIIa was analyzed. Docking studies were used in an attempt to rationalize the results. The (S)-isomers of both 2,3-dihydro-1,4-benzodioxine regioisomers at positions 6 and 7 were found to be better thrombin inhibitors than the corresponding (R)-enantiomers, whereas we observed that stereochemistry does not display a consistent influence on fibrinogen GPIIb/IIIa binding inhibitory activity. Compound 11b, the (S)-isomer of the 6-substituted regioisomer, possessed the best balanced dual activity, with K-i(thrombin) = 1.67 +/- 0.27 mu M and IC50(GPIIb/IIIa) = 0.665 +/- 0.26 mu M, raising the hope that merging anticoagulant and platelet antiaggregatory activities in the same molecule could lead to successful multitarget antithrombotic agents. (C) 2013 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2013.01.002