(6aR,9aS)-5,6a,7,8,9,9a-hexahydro-5-methyl-3-(methylsulfonyl)-2-(4-(6-fluoropyridin-2-yl)benzyl)-cyclopent[4,5]imidazo[1,2-a]pyrazolo[4,3-e]pyrimidin-4(2H)-one | 1228658-87-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: (6aR,9aS)-5,6a,7,8,9,9a-hexahydro-5-methyl-3-(methylsulfonyl)-2-(4-(6-fluoropyridin-2-yl)benzyl)-cyclopent[4,5]imidazo[1,2-a]pyrazolo[4,3-e]pyrimidin-4(2H)-one
• 英文别名: (11R,15S)-4-[[4-(6-fluoropyridin-2-yl)phenyl]methyl]-8-methyl-5-methylsulfonyl-1,3,4,8,10-pentazatetracyclo[7.6.0.02,6.011,15]pentadeca-2,5,9-trien-7-one
• CAS: 1228658-87-4
• 化学式: C₂₄H₂₃FN₆O₃S
• 分子量: 494.549
• InChiKey: NMDGAYFDPHVHKH-MSOLQXFVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  35
• 可旋转键数：
  4
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  109
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  (6aR,9aS)-5,6a,7,8,9,9a-hexahydro-5-methyl-3-(methylthio)-2-(4-(6-fluoropyridin-2-yl)benzyl)-cyclopent[4,5]imidazo[1,2-a]pyrazolo[4,3-e]pyrimidin-4(2H)-one 在 Oxone 作用下， 以 甲醇 、 水 、 乙腈 为溶剂， 反应 48.0h， 生成 (6aR,9aS)-5,6a,7,8,9,9a-hexahydro-5-methyl-3-(methylsulfonyl)-2-(4-(6-fluoropyridin-2-yl)benzyl)-cyclopent[4,5]imidazo[1,2-a]pyrazolo[4,3-e]pyrimidin-4(2H)-one
  参考文献：
  名称：

  [EN] ORGANIC COMPOUNDS
  [FR] COMPOSÉS ORGANIQUES

  摘要：

  可选择用3-(硫、磺酰基或磺酰亚基)-7,8-二氢-(1H或2H)-咪唑[1,2-a]吡唑并[4,3-e]嘧啶-4(5H)-酮或取代的3-(硫、亚磺酰基或磺酰基)-7,8,9-三氢-(1H或2H)-嘧啶并[1,2-a]吡唑并[4,3-e]嘧啶-4(5H)-酮化合物或公式(I)的化合物，其制备方法，其作为药物的用途以及包含它们的制药组合物。

  公开号：

  WO2010065149A1

文献信息

• ORGANIC COMPOUNDS
  申请人：Li Peng

  公开号：US20110245214A1

  公开（公告）日：2011-10-06

  Optionally substituted 3-(thio, sulfonyl or sulfonyl)-7,8-dihydro-(1H or 2H)-imidazo[1,2-a]pyrazolo[4,3-e]pyrimidin-4(5H)-one or a substituted 3-(thio, sulfinyl or sulfonyl)-7,8,9-trihydro-(1H or 2H)-pyrimido[1,2-a]pyrazolo[4,3-e]pyrimidin-4(5H)-one compounds or Compounds of Formula (I), processes for their production, their use as pharmaceuticals and pharmaceutical compositions comprising them.

  可选择地替代3-(硫、磺酰或磺酰基)-7,8-二氢-(1H或2H)-咪唑并[1,2-a]吡嗪并[4,3-e]嘧啶-4(5H)-酮或替代的3-(硫、亚磺酰或磺酰基)-7,8,9-三氢-(1H或2H)-嘧啶并[1,2-a]吡嗪并[4,3-e]嘧啶-4(5H)-酮化合物或式(I)的化合物，它们的制备方法，它们作为药物的用途以及包括它们的药物组合物。
• Organic compounds
  申请人：Li Peng

  公开号：US08536159B2

  公开（公告）日：2013-09-17

  Optionally substituted 3-(thio, sulfonyl or sulfonyl)-7,8-dihydro-(1H or 2H)-imidazo[1,2-a]pyrazolo[4,3-e]pyrimidin-4(5H)-one or a substituted 3-(thio, sulfinyl or sulfonyl)-7,8,9-trihydro-(1H or 2H)-pyrimido[1,2-a]pyrazolo[4,3-e]pyrimidin-4(5H)-one compounds or Compounds of Formula (I), processes for their production, their use as pharmaceuticals and pharmaceutical compositions comprising them.

  可选地替代3-(硫、磺酰或磺酰基)-7,8-二氢-(1H或2H)-咪唑并[1,2-a]吡嗪并[4,3-e]嘧啶-4(5H)-酮或替代的3-(硫、亚磺酰或磺酰基)-7,8,9-三氢-(1H或2H)-嘧啶并[1,2-a]吡嗪并[4,3-e]嘧啶-4(5H)-酮化合物或公式(I)的化合物，其生产过程，作为药物的用途以及包含它们的制药组合物。
• Combinations of PDE1 inhibitors and NEP inhibitors and associated methods
  申请人：Intra-Cellular Therapies, Inc.

  公开号：US10285992B2

  公开（公告）日：2019-05-14

  The invention relates to the combination of inhibitors of phosphodiesterase 1 (PDE1) and inhibitors of Neprilysin (NEP) useful for the treatment of certain cardiovascular diseases or related disorders, e.g., hypertension, congestive heart disease, and post-myocardial infarction. In another embodiment, the invention relates to the combination of inhibitors of PDE1 and inhibitors of NEP for the treatment of diseases or disorders characterized by disruption of or damage to various cGMP/PKG mediated pathways in the cardiovascular system (e.g., in cardiac tissue or in arterial smooth muscle).

  本发明涉及磷酸二酯酶1（PDE1）抑制剂和Neprilysin（NEP）抑制剂的组合，用于治疗某些心血管疾病或相关疾病，如高血压、充血性心脏病和心肌梗塞后。在另一个实施方案中，本发明涉及 PDE1 抑制剂和 NEP 抑制剂的组合，用于治疗以心血管系统（如心脏组织或动脉平滑肌）中各种 cGMP/PKG 介导的通路被破坏或损害为特征的疾病或紊乱。
• Uses
  申请人：INTRA-CELLULAR THERAPIES, INC.

  公开号：US10398698B2

  公开（公告）日：2019-09-03

  The invention relates to the administration of inhibitors of phosphodiesterase 1 (PDE1) for the treatment of diseases or disorders characterized by disruption of or damage to various cGMP/PKG mediated pathways. In one embodiment the invention relates to inhibitors of phosphodiesterase 1 (PDE1) for treatment of cardiovascular disease and related disorders, e.g., congestive heart disease, atherosclerosis, myocardial infarction, and stroke.

  本发明涉及磷酸二酯酶 1 (PDE1)抑制剂的施用，用于治疗以各种 cGMP/PKG 介导途径的破坏或损害为特征的疾病或紊乱。在一个实施方案中，本发明涉及用于治疗心血管疾病及相关疾病（如充血性心脏病、动脉粥样硬化、心肌梗塞和中风）的磷酸二酯酶1（PDE1）抑制剂。
• Combinations of PDE1 inhibitors and NEP inhibitors
  申请人：INTRA-CELLULAR THERAPIES, INC.

  公开号：US11166956B2

  公开（公告）日：2021-11-09

  The invention relates to the combination of inhibitors of phosphodiesterase 1 (PDE1) and inhibitors of Neprilysin (NEP) useful for the treatment of certain cardiovascular diseases or related disorders, e.g., hypertension, congestive heart disease, and post-myocardial infarction. In another embodiment, the invention relates to the combination of inhibitors of PDE1 and inhibitors of NEP for the treatment of diseases or disorders characterized by disruption of or damage to various cGMP/PKG mediated pathways in the cardiovascular system (e.g., in cardiac tissue or in arterial smooth muscle).

  本发明涉及磷酸二酯酶1（PDE1）抑制剂和Neprilysin（NEP）抑制剂的组合，用于治疗某些心血管疾病或相关疾病，如高血压、充血性心脏病和心肌梗塞后。在另一个实施方案中，本发明涉及 PDE1 抑制剂和 NEP 抑制剂的组合，用于治疗以心血管系统（如心脏组织或动脉平滑肌）中各种 cGMP/PKG 介导的通路被破坏或损害为特征的疾病或紊乱。