N,N-dimethyl-5-(3-(6-oxo-1,6-dihydropyrimidin-2-yl)-5-(tetrahydrofuran-3-yloxy)phenoxy)pyrimidine-2-carboxamide | 1352570-59-2

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: N,N-dimethyl-5-(3-(6-oxo-1,6-dihydropyrimidin-2-yl)-5-(tetrahydrofuran-3-yloxy)phenoxy)pyrimidine-2-carboxamide
• 英文别名: N,N-dimethyl-5-[3-(oxolan-3-yloxy)-5-(6-oxo-1H-pyrimidin-2-yl)phenoxy]pyrimidine-2-carboxamide
• CAS: 1352570-59-2
• 化学式: C₂₁H₂₁N₅O₅
• 分子量: 423.428
• InChiKey: HEKNCWVZFPPEJC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  31
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  115
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 0.5h， 生成 N,N-dimethyl-5-(3-(6-oxo-1,6-dihydropyrimidin-2-yl)-5-(tetrahydrofuran-3-yloxy)phenoxy)pyrimidine-2-carboxamide
  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

• [EN] 2-(3,5-DISUBSTITUTEDPHENYL)PYRIMIDIN-4(3H)-ONE DERIVATIVES<br/>[FR] DÉRIVÉS DE 2-(3,5-DISUBSTITUTEDPHENYL)PYRIMIDIN-4(3H)-ONE
  申请人：PFIZER

  公开号：WO2011158149A1

  公开（公告）日：2011-12-22

  O N NH R3 R2 O R1 168 ABSTRACT The present invention provides a 2-(3,5-disubstitutedphenyl)pyrimidin- 4(3H)-one compound of Formula (I) 5 (I) or a pharmaceutically acceptable salt thereof wherein R 1, R2 and R3 are as defined herein. The compounds of Formula (I) have been found to act as glucokinase activators. Consequently, the compounds of Formula (I) and 10 the pharmaceutical compositions thereof are useful for the treatment of diseases, disorders, or conditions mediated by glucokinase.

  本发明提供了一种Formula (I)的2-(3,5-二取代苯基)嘧啶-4(3H)-酮化合物或其药学上可接受的盐，其中R1、R2和R3如本文所定义。已发现Formula (I)的化合物可作为葡萄糖激酶激活剂。因此，Formula (I)的化合物及其药物组成物对于治疗由葡萄糖激酶介导的疾病、紊乱或症状是有用的。
• 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.