2,6-Dichloro-9-[(3-fluorophenyl)methyl]purine | 1044764-75-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 咪唑并嘧啶类
• 英文名称: 2,6-Dichloro-9-[(3-fluorophenyl)methyl]purine
• CAS: 1044764-75-1
• 化学式: C₁₂H₇Cl₂FN₄
• 分子量: 297.119
• InChiKey: CLVUWNHJRZCPPI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  19
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  43.6
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2,6-Dichloro-9-[(3-fluorophenyl)methyl]purine 在 水 、 sodium hydroxide 作用下， 反应 24.0h， 生成
  参考文献：
  名称：

  Synthesis and SAR development of novel P2X7 receptor antagonists for the treatment of pain: Part 2

  摘要：

  Novel P2X(7) antagonists were developed using a purine scaffold. These compounds were potent and selective at the P2X(7) receptor in human and rodent as well as efficacious in rodent pain models. Compound 15a was identified to have oral potency in several pain models in rodent similar to naproxen, gabapentin and pregabalin. Structure-activity relationship (SAR) development and results of pain models are presented. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.10.037
• 作为产物：
  描述：

  2,6-二氯嘌呤 、 间氟氯苄 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 24.0h， 生成 2,6-Dichloro-9-[(3-fluorophenyl)methyl]purine
  参考文献：
  名称：

  Synthesis and SAR development of novel P2X7 receptor antagonists for the treatment of pain: Part 2

  摘要：

  Novel P2X(7) antagonists were developed using a purine scaffold. These compounds were potent and selective at the P2X(7) receptor in human and rodent as well as efficacious in rodent pain models. Compound 15a was identified to have oral potency in several pain models in rodent similar to naproxen, gabapentin and pregabalin. Structure-activity relationship (SAR) development and results of pain models are presented. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.10.037

文献信息

• Structure-Based Development of Isoform-Selective Inhibitors of Casein Kinase 1ε vs Casein Kinase 1δ
  作者：Jun Yong Choi、Yoshihiko Noguchi、James M. Alburger、Simon Bayle、Eugene Chung、Wayne Grant、Apirat Chaikuad、Stefan Knapp、Derek R. Duckett、William R. Roush

  DOI：10.1021/acs.jmedchem.2c01180

  日期：2023.6.8

  Specific inhibition of a single kinase isoform is a challenging task due to the highly conserved nature of ATP-binding sites. Casein kinase 1 (CK1) δ and ε share 97% sequence identity in their catalytic domains. From a comparison of the X-ray crystal structures of CK1δ and CK1ε, we developed a potent and highly CK1ε-isoform-selective inhibitor (SR-4133). The X-ray co-crystal structure of the CK1δ−SR-4133

  由于 ATP 结合位点的高度保守性，对单一激酶亚型的特异性抑制是一项具有挑战性的任务。酪蛋白激酶 1 (CK1) δ 和 ε 在其催化结构域中具有 97% 的序列同一性。通过比较 CK1δ 和 CK1ε 的 X 射线晶体结构，我们开发了一种有效且高度 CK1ε 亚型选择性抑制剂 (SR-4133)。CK1δ−SR-4133 复合物的 X 射线共晶结构表明 SR-4133 的萘基单元和 CK1δ 之间的静电表面不匹配，从而破坏了 SR-4133 与 CK1δ 的相互作用。相反，CK1ε 的 Asp−Phe−Gly 基序 (DFG)-out 构象产生的疏水表面积稳定了 SR-4133 在 CK1ε ATP 结合袋中的结合，从而导致 CK1ε 的选择性抑制。