6-chloro-1-phenyl-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one | 6288-99-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 6-chloro-1-phenyl-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one
• 英文别名: 6-chloro-1-phenyl-1H,4H,5H-pyrazolo[3,4-d]pyrimidin-4-one；6-chloro-1-phenyl-5H-pyrazolo[3,4-d]pyrimidin-4-one
• CAS: 6288-99-9
• 化学式: C₁₁H₇ClN₄O
• mdl: MFCD18917258
• 分子量: 246.656
• InChiKey: GMXPVUMJGVSVLG-UHFFFAOYSA-N

物化性质

• 密度：
  1.58±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  17
• 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：
  59.3
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  6-chloro-1-phenyl-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one 在 碘 、 溶剂黄146 作用下， 以 乙醇 为溶剂， 反应 28.0h， 生成 8-iodomethyl-1-phenyl-7,8-dihydro-1H-imidazo[1,2-a]-pyrazolo[4,3-e]pyrimidin-4(6H)-one
  参考文献：
  名称：

  通过6-烯基（炔基）-氨基吡唑并[3,4-d]嘧啶-4的碘环化反应合成新的咪唑并[1,2- a]吡唑并[4,3-e]嘧啶-4（6 H）-one衍生物（5 H）-个

  摘要：

  6-烯丙基（二烯丙基，丙-2-炔-1-基）氨基-1-R-吡唑并[3,4- d ]嘧啶-4（5 H）-与碘反应生成角熔融的8-碘甲基-将7,8-二氢-1-R-咪唑并[1,2- a ]吡唑并[4,3 - e ]嘧啶-4（6 H）-用乙酸钠处理，得到8-亚甲基-1-R由于消除了碘化氢，得到了-7,8-二氢咪唑并[1,2- a ]吡唑并-[4,3 - e ]嘧啶-4（6 H）-。将8-亚甲基-1-R-7,8-二氢咪唑并[1,2- a ]吡唑并[4,3 - e ]嘧啶-4（6 H）-一转化为8-甲基-1-R-咪唑并[ 1,2- a ]吡唑并-[4,3- e] pyrimidin-4（5 H）-加热至熔点时为1。将8-亚甲基-1-苯基-7,8-二氢咪唑并[1,2- a ]吡唑并[4,3 - e ]嘧啶-4（6 H）-一异构化为线性稠合的6-甲基-1-苯基在硫酸中加热时，-1，8-二氢-4 H-咪唑并[1

  DOI：

  10.1134/s1070428011070165
• 作为产物：
  描述：

  5-氨基-1-苯基吡唑-4-甲酰胺 在 五氯化磷 、 potassium hydroxide 、 三氯氧磷 作用下， 生成 6-chloro-1-phenyl-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one
  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

• COMPOUNDS HAVING PDE9A INHIBITORY ACTIVITY, AND PHARMACEUTICAL USES THEREOF
  申请人：Korea Research Institute of Chemical Technology

  公开号：EP3892622A1

  公开（公告）日：2021-10-13

  The present invention provides a compound having a specific chemical structure and having PDE9A inhibitory activity, or a pharmaceutically acceptable salt thereof. The present invention provides a composition containing the compound or a pharmaceutically acceptable salt thereof. The present invention provides a pharmaceutical use, for treating or preventing PDE9A-related diseases, of the compound according to the present invention, a salt thereof, and a composition containing the compound or salt. The present invention also provides a method for treating or preventing PDE9A-related diseases, the method comprising administering an effective amount of the compound according to the present invention, a salt thereof, or a composition containing the compound or salt to a subject in need of treatment.

  本发明提供了一种具有特定化学结构并具有 PDE9A 抑制活性的化合物或其药学上可接受的盐。本发明提供了一种含有该化合物或其药学上可接受的盐的组合物。本发明提供了根据本发明的化合物、其盐和含有该化合物或盐的组合物的药物用途，用于治疗或预防 PDE9A 相关疾病。本发明还提供了一种治疗或预防PDE9A相关疾病的方法，该方法包括向需要治疗的受试者施用有效量的根据本发明的化合物、其盐或含有该化合物或盐的组合物。
• Potential Purine Antagonists. XII. Synthesis of 1-Alkyl(aryl)-4,6-disubstituted Pyrazolo[3,4-d]pyrimidines¹
  作者：C. C. CHENG、ROLAND K. ROBINS

  DOI：10.1021/jo01100a025

  日期：1958.6
• EP3892622
  申请人：——

  公开号：——

  公开（公告）日：——
• EP3892623
  申请人：——

  公开号：——

  公开（公告）日：——
• [EN] COMPOUNDS HAVING PDE9A INHIBITORY ACTIVITY, AND PHARMACEUTICAL USES THEREOF<br/>[FR] COMPOSÉS AYANT UNE ACTIVITÉ INHIBITRICE DE PDE9A ET LEURS UTILISATIONS PHARMACEUTIQUES<br/>[KO] PDE9A 저해 활성을 가지는 화합물 및 이들의 의약 용도
  申请人：KOREA RES INST CHEMICAL TECH

  公开号：WO2020116971A1

  公开（公告）日：2020-06-11

  본 발명은 PDE 9A를 저해하는 활성을 갖는 특정 화학구조의 화합물 또는 이의 약학적으로 허용 가능한 염을 제공한다. 본 발명은 이러한 화합물 또는 이의 약학적으로 허용 가능한 염을 포함하는 조성물을 제공한다. 본 발명은 본 발명에 따른 화합물, 이의 염 및 이들을 포함하는 조성물의 PDE 9A 관련 질환의 치료 또는 예방용 의약 용도를 제공한다. 본 발명은 또한 본 발명에 따른 화합물, 이의 염 또는 이들을 포함하는 조성물의 유효한 양을 치료가 필요한 개체에게 투여하는 것을 포함하는 PDE 9A 관련 질환의 치료 또는 예방 방법을 제공한다.