2-{5-[(4-ethyl-1-piperazinyl)sulfonyl]-2-(2-methoxyethoxy)-3-pyridinyl}-7,8,9,10-tetrahydropyrido[2',1':5,1]pyrazolo[4,3-d]pyrimidin-4(3H)-one

• 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: 2-{5-[(4-ethyl-1-piperazinyl)sulfonyl]-2-(2-methoxyethoxy)-3-pyridinyl}-7,8,9,10-tetrahydropyrido[2',1':5,1]pyrazolo[4,3-d]pyrimidin-4(3H)-one
• 英文别名: 4-[5-(4-Ethylpiperazin-1-yl)sulfonyl-2-(2-methoxyethoxy)pyridin-3-yl]-3,5,8,9-tetrazatricyclo[7.4.0.02,7]trideca-1,3,7-trien-6-one；4-[5-(4-ethylpiperazin-1-yl)sulfonyl-2-(2-methoxyethoxy)pyridin-3-yl]-3,5,8,9-tetrazatricyclo[7.4.0.02,7]trideca-1,3,7-trien-6-one
• 化学式: C₂₃H₃₁N₇O₅S
• 分子量: 517.609
• InChiKey: CVFPIXKMEFAIKC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.1
• 重原子数：
  36
• 可旋转键数：
  8
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  140
• 氢给体数：
  1
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  3-Bromo-2-ethoxy-5-(4-ethylpiperazin-1-ylsulphonyl)pyridine 在 四(三苯基膦)钯 、 草酰氯 、 双(三甲基硅烷基)氨基钾 、 三乙胺 、 sodium hydroxide 作用下， 以 乙醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 120.0 ℃ 、1.38 MPa 条件下， 反应 61.0h， 生成 2-{5-[(4-ethyl-1-piperazinyl)sulfonyl]-2-(2-methoxyethoxy)-3-pyridinyl}-7,8,9,10-tetrahydropyrido[2',1':5,1]pyrazolo[4,3-d]pyrimidin-4(3H)-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

• Pyrazolopyrimidine derivatives
  申请人：Pfizer Limited

  公开号：EP1241170A3

  公开（公告）日：2003-03-12

  The present invention provides a compound of formula (I): where Q is a group of formula:These compounds inhibit cyclic guanosine 3',5'-monophosphate phosphodiesterases (cGMP PDEs). More notably, the compounds are potent and selective inhibitors of the type 5 cyclic guanosine 3',5'-monophosphate phosphodiesterases and have utility therefore in a variety of therapeutic areas. In particular, the present compounds are of value for the curative or prophylactic treatment of mammalian sexual disorders.

  本发明提供了一个式（I）的化合物：其中Q是一个式的基团：这些化合物抑制环鸟苷3',5'-磷酸二酯酶（cGMP PDEs）。更重要的是，这些化合物是强效且选择性地抑制类型5环鸟苷3',5'-磷酸二酯酶，并因此在多种治疗领域中具有用途。特别是，目前的化合物对于治疗哺乳动物性功能障碍具有价值。
• Pharmaceutically active compounds
  申请人：——

  公开号：US20020193388A1

  公开（公告）日：2002-12-19

  The present invention provides a compound of formula (I): 1 where Q is a group of formula: 2 These compounds inhibit cyclic guanosine 3′,5′-monophosphate phosphodiesterases (cGMP PDES). More notably, the compounds are potent and selective inhibitors of the type 5 cyclic guanosine 3′,5′-monophosphate phosphodiesterases and have utility therefore in a variety of therapeutic areas. In particular, the present compounds are of value for the curative or prophylactic treatment of mammalian sexual disorders.

  本发明提供了一种化合物，其化学式为（I）：1其中Q是式子：2的一种基团。这些化合物能够抑制环磷鸟苷3′，5′-单磷酸磷酸二酯酶（cGMP PDES）。更重要的是，这些化合物是选择性抑制剂，具有强效抑制第5型环磷鸟苷3′，5′-单磷酸磷酸二酯酶的特点，因此在多种治疗领域有用。特别地，这些化合物对于治疗哺乳动物的性障碍具有治疗或预防价值。
• US6831074B2
  申请人：——

  公开号：US6831074B2

  公开（公告）日：2004-12-14
• 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.