5-(2-ethoxy-5-((4-methylpiperazin-1-yl)sulfonyl)phenyl)-3-propyl-1,6-dihydro-7H-pyrazolo[4,3-d]pyrimidin-7-one | 139755-95-6

• 物质功能分类: 分析化学 - 标准品 - 药典标准品和杂质标准品
• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 5-(2-ethoxy-5-((4-methylpiperazin-1-yl)sulfonyl)phenyl)-3-propyl-1,6-dihydro-7H-pyrazolo[4,3-d]pyrimidin-7-one
• 英文别名: 5-(2-ethoxy-5-((4-methylpiperazin-1-yl)sulfonyl)phenyl)-3-propyl-1H-pyrazolo[4,3-d]pyrimidin-7(6H)-one；N-desmethyl-sildenafil；UK-95,340；5-[2-Ethoxy-5-(4-methylpiperazinyl)sulphonylphenyl]-3-n-propyl-1,6-dihydro-7H-pyrazolo[4,3-d]pyrimidin-7-one；Pyrazole N-Demethyl Sildenafil；5-[2-ethoxy-5-(4-methylpiperazin-1-yl)sulfonylphenyl]-3-propyl-2,6-dihydropyrazolo[4,3-d]pyrimidin-7-one
• CAS: 139755-95-6
• 化学式: C₂₁H₂₈N₆O₄S
• mdl: MFCD18158995
• 分子量: 460.557
• InChiKey: ZLJVUHMTFSCAGQ-UHFFFAOYSA-N

物化性质

• 熔点：
  232-234°C
• 溶解度：
  DMF、DMSO（少许）、甲醇（少许）

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  32
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  128
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  3-碘吡啶 、 5-(2-ethoxy-5-((4-methylpiperazin-1-yl)sulfonyl)phenyl)-3-propyl-1,6-dihydro-7H-pyrazolo[4,3-d]pyrimidin-7-one 在 copper(l) iodide 、 caesium carbonate 、 trans-1,2-cyclohexanediamine 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 5-(2-ethoxy-5-((4-methylpiperazin-1-yl)sulfonyl)phenyl)-3-propyl-1-(pyridin-3-yl)-1H-pyrazolo[4,3-d]pyrimidin-7(6H)-one
  参考文献：
  名称：

  Synthesis and evaluation of human phosphodiesterases (PDE) 5 inhibitor analogs as trypanosomal PDE inhibitors. Part 1. Sildenafil analogs

  摘要：

  Parasitic diseases, such as African sleeping sickness, have a significant impact on the health and wellbeing in the poorest regions of the world. Pragmatic drug discovery efforts are needed to find new therapeutic agents. In this Letter we describe target repurposing efforts focused on trypanosomal phosphodiesterases. We outline the synthesis and biological evaluation of analogs of sildenafil (1), a human PDE5 inhibitor, for activities against trypanosomal PDEB1 (TbrPDEB1). We find that, while low potency analogs can be prepared, this chemical class is a sub-optimal starting point for further development of TbrPDE inhibitors. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.01.119
• 作为产物：
  描述：

  2-乙氧基-5-(4-甲基-1 哌嗪磺酰基)苯甲酸 在 sodium ethanolate 、 咪唑盐酸盐 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 反应 6.0h， 生成 5-(2-ethoxy-5-((4-methylpiperazin-1-yl)sulfonyl)phenyl)-3-propyl-1,6-dihydro-7H-pyrazolo[4,3-d]pyrimidin-7-one
  参考文献：
  名称：

  Synthesis and evaluation of human phosphodiesterases (PDE) 5 inhibitor analogs as trypanosomal PDE inhibitors. Part 1. Sildenafil analogs

  摘要：

  Parasitic diseases, such as African sleeping sickness, have a significant impact on the health and wellbeing in the poorest regions of the world. Pragmatic drug discovery efforts are needed to find new therapeutic agents. In this Letter we describe target repurposing efforts focused on trypanosomal phosphodiesterases. We outline the synthesis and biological evaluation of analogs of sildenafil (1), a human PDE5 inhibitor, for activities against trypanosomal PDEB1 (TbrPDEB1). We find that, while low potency analogs can be prepared, this chemical class is a sub-optimal starting point for further development of TbrPDE inhibitors. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.01.119

文献信息

• Pyrazolopyrimidinone antianginal agents
  申请人：Pfizer Inc.

  公开号：US05250534A1

  公开（公告）日：1993-10-05

  Compounds of the formula: ##STR1## wherein R.sup.1 is H, C.sub.1 -C.sub.3 alkyl, C.sub.3 -C.sub.5 cycloalkyl or C.sub.1 -C.sub.3 perfluoroalkyl; R.sup.2 is H, C.sub.1 -C.sub.6 alkyl optionally substituted by OH, C.sub.1 -C.sub.3 alkoxy or C.sub.3 -C.sub.6 cycloalkyl, or C.sub.1 -C.sub.3 perfluoroalkyl; R.sup.3 is C.sub.1 -C.sub.6 alkyl, C.sub.3 -C.sub.6 alkenyl, C.sub.3 -C.sub.6 alkynyl, C.sub.3 -C.sub.7 cycloalkyl, C.sub.1 -C.sub.6 perfluoroalkyl or (C.sub.3 -C.sub.6 cycloalkyl)C.sub.1 -C.sub.6 alkyl; R.sup.4 taken together with the nitrogen atom to which it is attached completes a pyrrolidinyl, piperidino, morpholino, or 4-N-(R.sup.6)-piperazinyl group; R.sup.5 is H, C.sub.1 -C.sub.4 alkyl, C.sub.1 -C.sub.3 alkoxy, NR.sup.7 R.sup.8, or CONR.sup.7 R.sup.8 ; R.sup.6 is H, C.sub.1 -C.sub.6 alkyl, (C.sub.1 -C.sub.3 alkoxy) C.sub.2 - C.sub.6 alkyl, hydroxy C.sub.2 -C.sub.6 alkyl, (R.sup.7 R.sup.8 N)C.sub.2 -C.sub.6 alkyl, (R.sup.7 R.sup.8 NCO)C.sub.1 -C.sub.6 alkyl, CONR.sup.7 R.sup.8, CSNR.sup.7 R.sup.8 or C(NH)NR.sup.7 R.sup.8 ; R.sup.7 and R.sup.8 are each independently H, C.sub.1 -C.sub.4 alkyl, (C.sub.1 -C.sub.3 alkoxy)C.sub.2 -C.sub.4 alkyl or hydroxy C.sub.2 -C.sub.4 alkyl; and pharmaceutically acceptable salts thereof, are selective cGMP PDE inhibitors useful in the treatment of cardiovascular disorders such as angina, hypertension, heart failure and atherosclerosis.

  该化合物的结构式为：##STR1## 其中R.sup.1为H，C.sub.1 -C.sub.3烷基，C.sub.3 -C.sub.5环烷基或C.sub.1 -C.sub.3全氟烷基；R.sup.2为H，C.sub.1 -C.sub.6烷基，可以选择性地被OH，C.sub.1 -C.sub.3烷氧基或C.sub.3 -C.sub.6环烷基，或C.sub.1 -C.sub.3全氟烷基取代；R.sup.3为C.sub.1 -C.sub.6烷基，C.sub.3 -C.sub.6烯基，C.sub.3 -C.sub.6炔基，C.sub.3 -C.sub.7环烷基，C.sub.1 -C.sub.6全氟烷基或(C.sub.3 -C.sub.6环烷基)C.sub.1 -C.sub.6烷基；R.sup.4与其连接的氮原子一起形成吡咯啉基、哌啶基、吗啉基或4-N-(R.sup.6)-哌嗪基；R.sup.5为H，C.sub.1 -C.sub.4烷基，C.sub.1 -C.sub.3烷氧基，NR.sup.7 R.sup.8，或CONR.sup.7 R.sup.8；R.sup.6为H，C.sub.1 -C.sub.6烷基，(C.sub.1 -C.sub.3烷氧基)C.sub.2 - C.sub.6烷基，羟基C.sub.2 -C.sub.6烷基，(R.sup.7 R.sup.8 N)C.sub.2 -C.sub.6烷基，(R.sup.7 R.sup.8 NCO)C.sub.1 -C.sub.6烷基，CONR.sup.7 R.sup.8，CSNR.sup.7 R.sup.8或C(NH)NR.sup.7 R.sup.8；R.sup.7和R.sup.8各自独立地为H，C.sub.1 -C.sub.4烷基，(C.sub.1 -C.sub.3烷氧基)C.sub.2 -C.sub.4烷基或羟基C.sub.2 -C.sub.4烷基；以及其药学上可接受的盐，是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的选择性cGMP PDE抑制剂。
• JPH11171879A
  申请人：——

  公开号：JPH11171879A

  公开（公告）日：1999-06-29
• US5250534A
  申请人：——

  公开号：US5250534A

  公开（公告）日：1993-10-05
• US5346901A
  申请人：——

  公开号：US5346901A

  公开（公告）日：1994-09-13
• US6200980B1
  申请人：——

  公开号：US6200980B1

  公开（公告）日：2001-03-13