2-ethyl-3-ethyl-5-[5-(4-ethylpiperazin-1-ylsulphonyl)-2-(2-methoxyethoxy)pyridin-3-yl]-2,6-dihydro-7H-pyrazolo[4,3-d]pyrimidin-7-one | 247582-32-7

• 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-ethyl-3-ethyl-5-[5-(4-ethylpiperazin-1-ylsulphonyl)-2-(2-methoxyethoxy)pyridin-3-yl]-2,6-dihydro-7H-pyrazolo[4,3-d]pyrimidin-7-one
• 英文别名: 2,3-Diethyl-5-[5-(4-ethylpiperazin-1-ylsulphonyl)-2-(2-methoxyethoxy)pyridin-3-yl]l-2,6-dihydro-7H-pyrazolo[4,3-d]pyrimidin-7-one；2,3-diethyl-5-[5-(4-ethylpiperazin-1-yl)sulfonyl-2-(2-methoxyethoxy)pyridin-3-yl]-6H-pyrazolo[4,3-d]pyrimidin-7-one
• CAS: 247582-32-7
• 化学式: C₂₃H₃₃N₇O₅S
• 分子量: 519.625
• InChiKey: OUZVHPZKCZEEIJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.5
• 重原子数：
  36
• 可旋转键数：
  10
• 环数：
  4.0
• 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：

  2-Ethoxy-5-(4-ethylpiperazin-1-ylsulphonyl)pyridine-3-carboxylic Acid Ethyl Ester 在 双(三甲基硅烷基)氨基钾 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 、 sodium hydroxide 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 反应 46.0h， 生成 2-ethyl-3-ethyl-5-[5-(4-ethylpiperazin-1-ylsulphonyl)-2-(2-methoxyethoxy)pyridin-3-yl]-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

• Pyridine-3-carboxylic acid derivatives and their use as intermediates
  申请人：PFIZER INC.

  公开号：EP1371647A2

  公开（公告）日：2003-12-17

  The present invention relates to compounds of the formula (X) which are useful in the synthesis of pyrazolopyrimidinone compounds: wherein: R13 is C1 to C4 alkyl optionally substituted with one or two substituents selected from OH, C1 to C4 alkoxy, benzyloxy, NR5R6, phenyl, furanyl and pyridinyl; C3 to C6 cycloalkyl; 1-(C1 to C4 alkyl)piperidinyl; tetrahydrofuranyl or tetrahydropyranyl; R4 is SO2NR7R8; R5 and R6 are each independently selected from H and C1 to C4 alkyl, or, together with the nitrogen atom to which they are attached, form a pyrrolidinyl, piperidinyl or morpholinyl group; R7 and R8, together with the nitrogen atom to which they are attached, form a 4-R10 piperazinyl group optionally substituted with one or two C1 to C4 alkyl groups and optionally in the form of its 4-N-oxide; R10 is H; C1 to C4 alkyl optionally substituted with one or two substituents selected from OH, NR5R6, CONR5R6, phenyl optionally substituted with C1 to C4 alkoxy, benzodioxolyl and benzodioxanyl; C3 to C6 alkenyl; pyridinyl or pyrimidinyl; or a salt of such compound, or an acid chloride derivative of such compound.

  本发明涉及式（X）化合物，该化合物可用于合成吡唑嘧啶酮化合物： 其中 R13 是任选被一个或两个取代基取代的 C1 至 C4 烷基，这些取代基选自 OH、C1 至 C4 烷氧基、苄氧基、NR5R6、苯基、呋喃基和吡啶基；C3 至 C6 环烷基；1-(C1 至 C4 烷基)哌啶基；四氢呋喃基或四氢吡喃基； R4 是 SO2NR7R8； R5 和 R6 各自独立地选自 H 和 C1 至 C4 烷基，或与它们连接的氮原子一起形成吡咯烷基、哌啶基或吗啉基； R7 和 R8 与它们所连接的氮原子一起形成 4-R10 哌嗪基团，该基团可选择被一个或两个 C1 至 C4 烷基取代，也可选择以其 4-N-oxide 的形式存在； R10 是 H；任选被一个或两个取代基取代的 C1 至 C4 烷基，这些取代基选自 OH、NR5R6、CONR5R6、任选被 C1 至 C4 烷氧基取代的苯基、苯并二噁茂基和苯并二噁烷基；C3 至 C6 烯基；吡啶基或嘧啶基； 或此类化合物的盐，或此类化合物的酸性氯化物衍生物。
• PYRAZOLOPYRIMIDINONE CGMP PDE5 INHIBITORS FOR THE TREATMENT OF SEXUAL DYSFUNCTION
  申请人：PFIZER INC.

  公开号：EP1073658B1

  公开（公告）日：2003-08-13
• US6251904B1
  申请人：——

  公开号：US6251904B1

  公开（公告）日：2001-06-26
• US6458951B2
  申请人：——

  公开号：US6458951B2

  公开（公告）日：2002-10-01
• 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.