5-(2-ethoxypyridin-3-yl)-1-methyl-3-propyl-1H-pyrazolo[4,3-d]pyrimidin-7(6H)-one | 1370409-75-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: 5-(2-ethoxypyridin-3-yl)-1-methyl-3-propyl-1H-pyrazolo[4,3-d]pyrimidin-7(6H)-one
• 英文别名: 5-(2-ethoxypyridin-3-yl)-1-methyl-3-propyl-6H-pyrazolo[4,3-d]pyrimidin-7-one
• CAS: 1370409-75-8
• 化学式: C₁₆H₁₉N₅O₂
• 分子量: 313.359
• InChiKey: WEWYYRBITOAPJH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  23
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  81.4
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  2-氯烟酸 在 potassium tert-butylate 、 三乙胺 、 bromo-tris(1-pyrrolidinyl)phosphonium hexafluorophosphate 作用下， 以 四氢呋喃 、 1,2-二氯乙烷 为溶剂， 反应 0.66h， 生成 5-(2-ethoxypyridin-3-yl)-1-methyl-3-propyl-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

文献信息

• 5-芳基-1H-吡唑并[4,3-d]嘧啶-7(6H)-酮的 合成工艺
  申请人：广州同隽医药科技有限公司

  公开号：CN104804003B

  公开（公告）日：2017-07-28

  本发明公开了5‑芳基‑1H‑吡唑并[4,3‑d]嘧啶‑7(6H)‑酮的合成工艺，该包括如下步骤：将取代芳基醛与1‑甲基‑3‑丙基‑4‑氨基吡唑‑5‑甲酰胺混合，缩合得到亚胺中间体；将亚胺中间体于溶剂中在成环剂和助氧剂的共同作用下，环合氧化得到5‑芳基‑1H‑吡唑并[4,3‑d]嘧啶‑7(6H)‑酮。本发明的合成工艺反应条件温和，大大提高了环合氧化反应的转化率、缩短了反应时间、减少了副反应的产生。反应既可以分两步分别在不同的反应器中进行，也可以在同一反应器内进行。分步合成法有利于中间体的质量控制和产品的纯化，一步合成法简化了合成工序和缩短了反应时间，均能有效的合成5‑芳基‑1H‑吡唑并[4,3‑d]嘧啶‑7(6H)‑酮。使用的试剂基本为无毒或低毒，同时价格低廉，合成成本低。
• Synthesis and evaluation of human phosphodiesterases (PDE) 5 inhibitor analogs as trypanosomal PDE inhibitors. Part 1. Sildenafil analogs
  作者：Cuihua Wang、Trent D. Ashton、Alden Gustafson、Nicholas D. Bland、Stefan O. Ochiana、Robert K. Campbell、Michael P. Pollastri

  DOI：10.1016/j.bmcl.2012.01.119

  日期：2012.4

  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.