3-[(2S)-1-hydroxypropan-2-yl]oxy-5-[4-[(4-methoxyphenyl)methoxy]pyrimidin-2-yl]phenol | 1448788-57-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 3-[(2S)-1-hydroxypropan-2-yl]oxy-5-[4-[(4-methoxyphenyl)methoxy]pyrimidin-2-yl]phenol
• CAS: 1448788-57-5
• 化学式: C₂₁H₂₂N₂O₅
• 分子量: 382.416
• InChiKey: ZNPFULDXJGJLEE-AWEZNQCLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  28
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  93.9
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  5-溴-嘧啶-2-羧酸二甲基酰胺 、 3-[(2S)-1-hydroxypropan-2-yl]oxy-5-[4-[(4-methoxyphenyl)methoxy]pyrimidin-2-yl]phenol 在 2,2,6,6-四甲基-3,5-庚二酮 、 caesium carbonate 、 copper(l) chloride 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 15.0h， 生成
  参考文献：
  名称：

  Pyrimidone-based series of glucokinase activators with alternative donor–acceptor motif

  摘要：

  Glucokinase activators are a class of experimental agents under investigation as a therapy for Type 2 diabetes mellitus. An X-ray crystal structure of a modestly potent agent revealed the potential to substitute the common heterocyclic amide donor-acceptor motif for a pyridone moiety. We have successfully demonstrated that both pyridone and pyrimidone heterocycles can be used as a potent donor-acceptor substituent. Several sub-micromolar analogs that possess the desired partial activator profile were synthesized and characterized. Unfortunately, the most potent activators suffered from sub-optimal pharmacokinetic properties. Nonetheless, these donor-acceptor motifs may find utility in other glucokinase activator series or beyond. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.06.036
• 作为产物：
  描述：

  5-溴-1,3-苯二酚 在 咪唑 、 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 、 偶氮二甲酸二异丙酯 、 四丁基氟化铵 、 叔丁基锂 、 sodium carbonate 、 三苯基膦 作用下， 以 四氢呋喃 、 乙二醇二甲醚 、 二氯甲烷 、 水 、 正戊烷 为溶剂， 反应 129.0h， 生成 3-[(2S)-1-hydroxypropan-2-yl]oxy-5-[4-[(4-methoxyphenyl)methoxy]pyrimidin-2-yl]phenol
  参考文献：
  名称：

  Pyrimidone-based series of glucokinase activators with alternative donor–acceptor motif

  摘要：

  Glucokinase activators are a class of experimental agents under investigation as a therapy for Type 2 diabetes mellitus. An X-ray crystal structure of a modestly potent agent revealed the potential to substitute the common heterocyclic amide donor-acceptor motif for a pyridone moiety. We have successfully demonstrated that both pyridone and pyrimidone heterocycles can be used as a potent donor-acceptor substituent. Several sub-micromolar analogs that possess the desired partial activator profile were synthesized and characterized. Unfortunately, the most potent activators suffered from sub-optimal pharmacokinetic properties. Nonetheless, these donor-acceptor motifs may find utility in other glucokinase activator series or beyond. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.06.036

文献信息

• Pyrimidone-based series of glucokinase activators with alternative donor–acceptor motif
  作者：Kevin J. Filipski、Angel Guzman-Perez、Jianwei Bian、Christian Perreault、Gary E. Aspnes、Mary T. Didiuk、Robert L. Dow、Richard F. Hank、Christopher S. Jones、Robert J. Maguire、Meihua Tu、Dongxiang Zeng、Shenping Liu、John D. Knafels、John Litchfield、Karen Atkinson、David R. Derksen、Francis Bourbonais、Ketan S. Gajiwala、Michael Hickey、Theodore O. Johnson、Paul S. Humphries、Jeffrey A. Pfefferkorn

  DOI：10.1016/j.bmcl.2013.06.036

  日期：2013.8

  Glucokinase activators are a class of experimental agents under investigation as a therapy for Type 2 diabetes mellitus. An X-ray crystal structure of a modestly potent agent revealed the potential to substitute the common heterocyclic amide donor-acceptor motif for a pyridone moiety. We have successfully demonstrated that both pyridone and pyrimidone heterocycles can be used as a potent donor-acceptor substituent. Several sub-micromolar analogs that possess the desired partial activator profile were synthesized and characterized. Unfortunately, the most potent activators suffered from sub-optimal pharmacokinetic properties. Nonetheless, these donor-acceptor motifs may find utility in other glucokinase activator series or beyond. (C) 2013 Elsevier Ltd. All rights reserved.