1-(2-chlorophenyl)-7H-pyrazolo[3,4-d]pyrimidine-4,6-dione | 1251465-35-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 1-(2-chlorophenyl)-7H-pyrazolo[3,4-d]pyrimidine-4,6-dione
• CAS: 1251465-35-6
• 化学式: C₁₁H₇ClN₄O₂
• 分子量: 262.655
• InChiKey: FCIPKXZDTBDRTC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  18
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  76
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1-(2-chlorophenyl)-7H-pyrazolo[3,4-d]pyrimidine-4,6-dione 在 五氯化磷 、 三乙胺 、 异丙醇 、 potassium hydroxide 、 三氯氧磷 作用下， 反应 6.0h， 生成 2-((1-(2-chlorophenyl)-4-hydroxy-1H-pyrazolo[3,4-d]pyrimidin-6-yl)amino)-N-(4-isopropoxyphenyl)propanamide
  参考文献：
  名称：

  Structure-Based Discovery of Highly Selective Phosphodiesterase-9A Inhibitors and Implications for Inhibitor Design

  摘要：

  A new series of phosphodiesterase-9 (PDE9) inhibitors that contain a scaffold of 6-amino-pyrazolopyrimidinone have been discovered by a combination of structure-based design and computational docking. This procedure significantly saved the load of chemical synthesis and is an effective method for the discovery of inhibitors. The best compound 28 has an IC50 of 21 nM and 3.3 mu M, respectively, for PDE9 and PDE5 and about 3 orders of magnitude of selectivity against other PDE families. The crystal structure of the PDE9 catalytic domain in complex with 28 has been determined and shows a hydrogen bond between 28 and Tyr424. This hydrogen bond may account for the 860-fold selectivity of 28 against PDE1B, in comparison with about 30-fold selectivity of BAY73-6691. Thus, our studies suggest that Tyr424, a unique residue of PDE8 and PDE9, is a potential target for improvement of selectivity of PDE9 inhibitors.

  DOI：

  10.1021/jm301189c
• 作为产物：
  描述：

  (2-氯苯基)-肼 在 双氧水 、 Ammonium hydroxide 作用下， 以 乙醇 为溶剂， 生成 1-(2-chlorophenyl)-7H-pyrazolo[3,4-d]pyrimidine-4,6-dione
  参考文献：
  名称：

  Structure-Based Discovery of Highly Selective Phosphodiesterase-9A Inhibitors and Implications for Inhibitor Design

  摘要：

  A new series of phosphodiesterase-9 (PDE9) inhibitors that contain a scaffold of 6-amino-pyrazolopyrimidinone have been discovered by a combination of structure-based design and computational docking. This procedure significantly saved the load of chemical synthesis and is an effective method for the discovery of inhibitors. The best compound 28 has an IC50 of 21 nM and 3.3 mu M, respectively, for PDE9 and PDE5 and about 3 orders of magnitude of selectivity against other PDE families. The crystal structure of the PDE9 catalytic domain in complex with 28 has been determined and shows a hydrogen bond between 28 and Tyr424. This hydrogen bond may account for the 860-fold selectivity of 28 against PDE1B, in comparison with about 30-fold selectivity of BAY73-6691. Thus, our studies suggest that Tyr424, a unique residue of PDE8 and PDE9, is a potential target for improvement of selectivity of PDE9 inhibitors.

  DOI：

  10.1021/jm301189c

文献信息

• [EN] ANTIVIRAL PYRIMIDINES<br/>[FR] PYRIMIDINES ANTIVIRALES
  申请人：PROGENICS PHARM INC

  公开号：WO2010118367A3

  公开（公告）日：2011-03-10