N-(3-carbamoyl-5-ethyl-1-(2-morpholinoethyl)-1H-pyrazol-4-yl)-2-ethoxy-5-((4-ethylpiperazin-1-yl)sulfonyl)nicotinamide | 1356129-73-1

• 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: N-(3-carbamoyl-5-ethyl-1-(2-morpholinoethyl)-1H-pyrazol-4-yl)-2-ethoxy-5-((4-ethylpiperazin-1-yl)sulfonyl)nicotinamide
• CAS: 1356129-73-1
• 化学式: C₂₆H₄₀N₈O₆S
• 分子量: 592.72
• InChiKey: JLJMIXVDXJSLPZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.25
• 重原子数：
  41.0
• 可旋转键数：
  12.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  165.22
• 氢给体数：
  2.0
• 氢受体数：
  11.0

反应信息

• 作为反应物：
  描述：

  N-(3-carbamoyl-5-ethyl-1-(2-morpholinoethyl)-1H-pyrazol-4-yl)-2-ethoxy-5-((4-ethylpiperazin-1-yl)sulfonyl)nicotinamide 在 双(三甲基硅烷基)氨基钾 作用下， 以 乙醇 为溶剂， 反应 6.0h， 生成 5-[2-ethoxy-5-(4-ethylpiperazin-1-ylsulphonyl)pyridin-3-yl]-3-ethyl-[2-(morpholin-4-yl)ethyl]-2,6-dihydro-7H-pyrazolo[4,3-d]pyrimidin-7-one
  参考文献：
  名称：

  The discovery of UK-369003, a novel PDE5 inhibitor with the potential for oral bioavailability and dose-proportional pharmacokinetics

  摘要：

  This paper describes our recent efforts to design and synthesise potent and selective PDE5 inhibitors and the use of in vitro predictors of clearance, absorption and permeability to maximise the potential for dose-proportional pharmacokinetics and good oral bioavailability in man. Optimisation of the preclinical profile resulted in the identification of UK-369003 (19a) and its nomination as a clinical candidate. The clinical pharmacokinetic and safety profile has enabled us to progress the compound to test its efficacy in patients with lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH) and a paper describing its efficacy has recently been published. 2,3 (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.10.022
• 作为产物：
  描述：

  2-氨基吡啶 在 盐酸 、 四(三苯基膦)钯 、 硫酸 、 三氧化硫 、 溴 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 、 N,N-二异丙基乙胺 、 sodium hydroxide 、 sodium nitrite 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 、 水 为溶剂， 140.0 ℃ 、1.38 MPa 条件下， 反应 68.5h， 生成 N-(3-carbamoyl-5-ethyl-1-(2-morpholinoethyl)-1H-pyrazol-4-yl)-2-ethoxy-5-((4-ethylpiperazin-1-yl)sulfonyl)nicotinamide
  参考文献：
  名称：

  The discovery of UK-369003, a novel PDE5 inhibitor with the potential for oral bioavailability and dose-proportional pharmacokinetics

  摘要：

  This paper describes our recent efforts to design and synthesise potent and selective PDE5 inhibitors and the use of in vitro predictors of clearance, absorption and permeability to maximise the potential for dose-proportional pharmacokinetics and good oral bioavailability in man. Optimisation of the preclinical profile resulted in the identification of UK-369003 (19a) and its nomination as a clinical candidate. The clinical pharmacokinetic and safety profile has enabled us to progress the compound to test its efficacy in patients with lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH) and a paper describing its efficacy has recently been published. 2,3 (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.10.022