5-[2-iso-butoxy-5-(4-ethylpiperazin-1-ylsulphonyl)pyridin-3-yl]-2-[2-(dimethylamino)ethyl]-3-ethyl-2,6-dihydro-7H-pyrazolo[4,3-d]pyrimidin-7-one | 334827-49-5

• 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-iso-butoxy-5-(4-ethylpiperazin-1-ylsulphonyl)pyridin-3-yl]-2-[2-(dimethylamino)ethyl]-3-ethyl-2,6-dihydro-7H-pyrazolo[4,3-d]pyrimidin-7-one
• 英文别名: 2-[2-(dimethylamino)ethyl]-3-ethyl-5-[5-(4-ethylpiperazin-1-yl)sulfonyl-2-(2-methylpropoxy)pyridin-3-yl]-6H-pyrazolo[4,3-d]pyrimidin-7-one
• CAS: 334827-49-5
• 化学式: C₂₆H₄₀N₈O₄S
• 分子量: 560.721
• InChiKey: DCKVZKCSDFTFMA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.67
• 重原子数：
  39.0
• 可旋转键数：
  11.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  129.55
• 氢给体数：
  1.0
• 氢受体数：
  10.0

反应信息

• 作为产物：
  描述：

  异丁醇 、 N-[3-carbamoyl-1-[2-(dimethylamino)ethyl]-5-ethylpyrazol-4-yl]-2-ethoxy-5-(4-ethylpiperazin-1-yl)sulfonylpyridine-3-carboxamide 在 双(三甲基硅烷基)氨基钾 作用下， 以 乙酸乙酯 为溶剂， 反应 6.0h， 以23%的产率得到5-[2-iso-butoxy-5-(4-ethylpiperazin-1-ylsulphonyl)pyridin-3-yl]-2-[2-(dimethylamino)ethyl]-3-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

文献信息

• The discovery of UK-369003, a novel PDE5 inhibitor with the potential for oral bioavailability and dose-proportional pharmacokinetics
  作者：David J. Rawson、Stephen Ballard、Christopher Barber、Laura Barker、Kevin Beaumont、Mark Bunnage、Susan Cole、Martin Corless、Stephen Denton、David Ellis、Marion Floc’h、Laura Foster、James Gosset、Frances Holmwood、Charlotte Lane、David Leahy、John Mathias、Graham Maw、William Million、Cedric Poinsard、Jenny Price、Rachel Russel、Stephen Street、Lesa Watson

  DOI：10.1016/j.bmc.2011.10.022

  日期：2012.1

  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.