5-[5-(4-acetyl-1-piperazinyl)acetyl-2-ethoxyphenyl]-1-methyl-3-n-propyl-1,6-dihydro-7H-pyrazolo[4,3-d]pyrimidin-7-one

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 5-[5-(4-acetyl-1-piperazinyl)acetyl-2-ethoxyphenyl]-1-methyl-3-n-propyl-1,6-dihydro-7H-pyrazolo[4,3-d]pyrimidin-7-one
• 英文别名: 5-[5-[2-(4-acetylpiperazin-1-yl)acetyl]-2-ethoxyphenyl]-1-methyl-3-propyl-6H-pyrazolo[4,3-d]pyrimidin-7-one
• 化学式: C₂₅H₃₂N₆O₄
• 分子量: 480.567
• InChiKey: XASSLBVBJPIEBC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  35
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  109
• 氢给体数：
  1
• 氢受体数：
  6

文献信息

• Pyrazolopyrimidinone antianginal agents
  申请人：Pfizer Limited

  公开号：EP0526004A1

  公开（公告）日：1993-02-03

  Compounds of formula: and pharmaceutically acceptable salts thereof, wherein    R¹ is H; C₁-C₃ alkyl optionally substituted with one or more fluoro substituents; or C₃-C₅ cycloalkyl; R² is H, or C₁-C₆ alkyl optionally susbtituted with one or more fluoro subtituents or with C₃-C₆ cycloalkyl; R³ is C₁-C₆ alkyl optionally substituted with one or more fluoro substituents or with C₃-C₆ cycloalkyl; C₃-C₅ cycloalkyl; C₃-C₆ alkenyl; or C₃-C₆ alkynyl; R⁴ is C₁-C₄ alkyl optionally substituted with OH, NR⁵R⁶, CN, CONR⁵R⁶ or CO₂R⁷; C₂-C₄ alkenyl optionally substituted with CN, CONR⁵R⁶ or CO₂R⁷; C₂-C₄ alkanoyl optionally substituted with NR⁵R⁶; hydroxy C₂-C₄ alkyl optionally susbtituted with NR⁵R⁶; (C₂-C₃ alkoxy)C₁-C₂ alkyl optionally substituted with OH or NR⁵R⁶; CONR⁵R⁶; CO₂R⁷; halo; NR⁵R⁶; NHSO₂NR⁵R⁶; NHSO₂R⁸; or phenyl or heterocyclyl either of which is optionally substituted with methyl; R⁵ and R⁶ are each independently H or C₁-C₄ alkyl, or together with the nitrogen atom to which they are attached from a pyrrolidinyl, piperidino, morpholino, 4-(NR⁹)-piperazinyl or imidazoyl group wherein said group is optionally substituted with methyl or hydroxy; R⁷ is H or C₁-C₄ alkyl; R⁸ is C₁-C₃ alkyl optionally substituted with NR⁵R⁶; and R⁹ is H; C₁-C₃ alkyl optionally substituted with phenyl; hydroxy C₂-C₃ alkyl; or C₁-C₄ alkanoyl; are selective cGMP PDE inhibitors useful in the treatment of cardiovascular disorders such as angina, hypertension, heart failure and atherosclerosis.

  式的化合物： 及其药学上可接受的盐类、 其中 R¹ 是 H；任选被一个或多个氟取代基取代的 C₁-C₃ 烷基；或 C₃-C₅ 环烷基；R² 是 H，或任选被一个或多个氟取代基取代的 C₁-C₆ 烷基，或 C₃-C₆ 环烷基；R³ 是任选被一个或多个氟取代基取代的 C₁-C₆ 烷基，或 C₃-C₆ 环烷基；C₃-C₅ 环烷基；C₃-C₆ 烯基；或 C₃-C₆ 烷炔基；R⁴ 是可选被 OH、NR⁵R⁶、CN、CONR⁵R⁶ 或 CO₂R⁷ 取代的 C₁-C₄ 烷基；任选被 CN、CONR⁵R⁶ 或 CO₂R⁷取代的 C₂-C₄ 烯基；任选被 NR⁵R⁶ 取代的 C₂-C₄ 烷酰基；羟基 C₂-C₄烷基，可选被 NR⁵R⁶取代； (C₂-C₃ 烷氧基)C₁-C₂烷基，可选被 OH 或 NR⁵R⁶ 取代；CONR⁵R⁶；CO₂R⁷；卤素；NR⁵R⁶；NHSO₂NR⁵R⁶；NHSO₂R⁸；或任选被甲基取代的苯基或杂环基；R⁵ 和 R⁶ 各自独立地为 H 或 C₁-C₄ 烷基，或与氮原子相连的吡咯烷基、哌啶基、吗啉基、4-(NR⁹)-哌嗪基或咪唑酰基，其中所述基团任选被甲基或羟基取代；R⁷ 是 H 或 C₁-C₄ 烷基；R⁸ 是 C₁-C₃ 烷基，可选择被 NR⁵R⁶ 取代； R⁹是H；任选被苯基取代的C₁-C₃烷基；羟基C₂-C₃烷基；或C₁-C₄烷酰基； 是选择性 cGMP PDE 抑制剂，可用于治疗心血管疾病，如心绞痛、高血压、心力衰竭和动脉粥样硬化。
• Pharmaceutical compositions for treating nitrate-induced tolerance
  申请人：Pfizer Limited

  公开号：EP1022026A2

  公开（公告）日：2000-07-26

  The present invention relates to methods for treating nitrate-induced tolerance in a mammal by administering a nitrate-induced tolerance treating amount of a compound of formulae (I), (II), (III) (IV), (V), (VI), (VII), (VIII), (IX), (XA) or (XB) as defined herein, or the pharmaceutically acceptable salts, prodrugs, polymorphs, hydrates, solvates, active metabolites or stereoisomers thereof. The invention also relates to pharmaceutical compositions for the treatment of nitrate-induced tolerance in a mammal comprising a nitrate-induced tolerance treating amount of a compound of formulae (I), (II), (III) (lV), (V), (VI), (VII), (VIII), (IX), (XA) or (XB) as defined herein, or the pharmaceutically acceptable salts, prodrugs, polymorphs, hydrates, solvates, active metabolites or stereoisomers thereof, and a pharmaceutically acceptable vehicle, diluent or carrier. The invention further relates to methods of preventing nitrate-induced tolerance in a mammal comprising administering a nitrate-induced tolerance preventing amount of a cGMP PDE inhibitor.

  本发明涉及通过施用本文定义的式(I)、(II)、(III)(IV)、(V)、(VI)、(VII)、(VIII)、(IX)、(XA)或(XB)化合物或其药学上可接受的盐、原药、多晶型物、水合物、溶解物、活性代谢物或立体异构体的硝酸盐诱导的耐受性治疗量来治疗哺乳动物的硝酸盐诱导的耐受性的方法。本发明还涉及用于治疗哺乳动物硝酸盐诱导耐受性的药物组合物，其包含硝酸盐诱导耐受性治疗量的式(I)、(II)、(III)(lV)、(V)、(VI)、(VII)、(VIII)、(IX)、(XA)或(XB)，或其药学上可接受的盐、原药、多晶型物、水合物、溶解物、活性代谢物或立体异构体，以及药学上可接受的载体、稀释剂或载体。本发明还涉及防止哺乳动物产生硝酸盐耐受性的方法，包括施用一定量的 cGMP PDE 抑制剂，以防止产生硝酸盐耐受性。
• US5272147A
  申请人：——

  公开号：US5272147A

  公开（公告）日：1993-12-21
• US5426107A
  申请人：——

  公开号：US5426107A

  公开（公告）日：1995-06-20
• US6225315B1
  申请人：——

  公开号：US6225315B1

  公开（公告）日：2001-05-01