methyl (1R,3R,4R,5S)-5-acetamido-1-benzyloxy-3-[2-(4-chlorobenzamido)ethoxy]-4-(2-fluoroacetamido)-cyclohexane-1-carboxylate | 1257059-94-1

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: methyl (1R,3R,4R,5S)-5-acetamido-1-benzyloxy-3-[2-(4-chlorobenzamido)ethoxy]-4-(2-fluoroacetamido)-cyclohexane-1-carboxylate
• CAS: 1257059-94-1
• 化学式: C₂₈H₃₃ClFN₃O₇
• 分子量: 578.037
• InChiKey: LKMARNVMQQCZPL-ZJTSJXPUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.34
• 重原子数：
  40.0
• 可旋转键数：
  12.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  132.06
• 氢给体数：
  3.0
• 氢受体数：
  7.0

反应信息

• 作为反应物：
  描述：

  methyl (1R,3R,4R,5S)-5-acetamido-1-benzyloxy-3-[2-(4-chlorobenzamido)ethoxy]-4-(2-fluoroacetamido)-cyclohexane-1-carboxylate 在 lithium hydroxide monohydrate 、 水 、 溶剂黄146 作用下， 以 四氢呋喃 、 甲醇 、 水 为溶剂， 以83%的产率得到sodium (1R,3R,4R,5S)-5-acetamido-1-benzyloxy-3-[2-(4-chlorobenzamido)ethoxy]-4-(2-fluoroacetamido)-cyclohexane-1-carboxylate
  参考文献：
  名称：

  Design, synthesis, biological evaluation, and modeling of a non-carbohydrate antagonist of the myelin-associated glycoprotein

  摘要：

  Broad modifications of various positions of the minimal natural epitope recognized by the myelin-associated glycoprotein (MAG), a blocker of regeneration of neurite injuries, produced sialosides with nanomolar affinities. However, important pharmacokinetic issues, for example, the metabolic stability of these sialosides, remain to be addressed. For this reason, the novel non-carbohydrate mimic 3 was designed and synthesized from (-)-quinic acid. For the design of 3, previously identified beneficial modifications of side chains of Neu5Ac were combined with the replacement of the ring oxygen by a methylene group and the substitution of the C(4)-OH by an acetamide. Although docking experiments to a homology model of MAG revealed that mimic 3 forms all but one of the essential hydrogen bonds identified for the earlier reported lead 2, its affinity was substantially reduced. Extensive molecular-dynamics simulation disclosed that the missing hydrogen bond of the former C(8)-OH leads to a change of the orientation of the side chain. As a consequence, an important hydrophobic contact is compromised leading to a loss of affinity. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2010.08.027
• 作为产物：
  描述：

  氟代乙酰氯 、 在 4-二甲氨基吡啶 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 以19.7 mg的产率得到methyl (1R,3R,4R,5S)-5-acetamido-1-benzyloxy-3-[2-(4-chlorobenzamido)ethoxy]-4-(2-fluoroacetamido)-cyclohexane-1-carboxylate
  参考文献：
  名称：

  Design, synthesis, biological evaluation, and modeling of a non-carbohydrate antagonist of the myelin-associated glycoprotein

  摘要：

  Broad modifications of various positions of the minimal natural epitope recognized by the myelin-associated glycoprotein (MAG), a blocker of regeneration of neurite injuries, produced sialosides with nanomolar affinities. However, important pharmacokinetic issues, for example, the metabolic stability of these sialosides, remain to be addressed. For this reason, the novel non-carbohydrate mimic 3 was designed and synthesized from (-)-quinic acid. For the design of 3, previously identified beneficial modifications of side chains of Neu5Ac were combined with the replacement of the ring oxygen by a methylene group and the substitution of the C(4)-OH by an acetamide. Although docking experiments to a homology model of MAG revealed that mimic 3 forms all but one of the essential hydrogen bonds identified for the earlier reported lead 2, its affinity was substantially reduced. Extensive molecular-dynamics simulation disclosed that the missing hydrogen bond of the former C(8)-OH leads to a change of the orientation of the side chain. As a consequence, an important hydrophobic contact is compromised leading to a loss of affinity. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2010.08.027