7-氯-3-[4-(2-羟基乙基)-1-哌嗪基]-1-(2-丙氧乙基)-吡啶并[3,4-b]吡嗪-2(1H)-酮 | 954138-53-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 中文名称: 7-氯-3-[4-(2-羟基乙基)-1-哌嗪基]-1-(2-丙氧乙基)-吡啶并[3,4-b]吡嗪-2(1H)-酮
• 英文名称: 7-chloro-3-(4-(2-hydroxyethyl)piperazin-1-yl)-1-(2-propoxyethyl)pyrido[3,4-b]pyrazin-2(1H)-one
• 英文别名: 7-chloro-3-[4-(2-hydroxyethyl)piperazin-1-yl]-1-(2-propoxyethyl)-1H,2H-pyrido[3,4-b]pyrazin-2-one；7-chloro-3-[4-(2-hydroxyethyl)piperazin-1-yl]-1-(2-propoxyethyl)pyrido[3,4-b]pyrazin-2-one
• CAS: 954138-53-5
• 化学式: C₁₈H₂₆ClN₅O₃
• 分子量: 395.889
• InChiKey: KJTAQYDHXJLWHN-UHFFFAOYSA-N

物化性质

• 沸点：
  575.2±60.0 °C(Predicted)
• 密度：
  1.37±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  27
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.61
• 拓扑面积：
  81.5
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  7-氯-3-[4-(2-羟基乙基)-1-哌嗪基]-1-(2-丙氧乙基)-吡啶并[3,4-b]吡嗪-2(1H)-酮 在 四(三苯基膦)钯 、 三甲胺盐酸盐 、 三乙胺 作用下， 以 1,4-二氧六环 、 二氯甲烷 为溶剂， 反应 32.08h， 生成 2-(4-(1,2-dihydro-7-(6-methoxypyridin-3-yl)-2-oxo-1-(2-propoxyethyl)pyrido[3,4-b]pyrazin-3-yl)piperazin-1-yl)ethyl 4-methylbenzenesulfonate
  参考文献：
  名称：

  Carbon-11 and Fluorine-18 Radiolabeled Pyridopyrazinone Derivatives for Positron Emission Tomography (PET) Imaging of Phosphodiesterase-5 (PDE5)

  摘要：

  The cyclic guanosine monophosphate (cGMP) specific phosphodiesterase type 5 (PDES) plays an important role in various pathologies including pulmonary arterial hypertension and cardiomyopathy. PDES represents an important therapeutic and/or prognostic target, but noninvasive assessment of PDE5 expression is lacking. The purpose of this study was to: develop and evaluate pyridopyrazinone derivatives labeled with carbon-11 or fluorine-18 as PDE5-specific PET tracers. In biodistribution studies, highest PDE5-specific retention was observed for [C-11]-12 and [F-18]-17 in the lungs of wild-type mice and in the myocardium of transgenic mice with cardiomyocyte-specific PDES overexpression at 30 min postinjection. In-vivo dynamic microPET images in rats revealed that both tracers crossed the blood-brain barrier but brain retention was not PDE5-specific. Both [C-11]-.1.2 and [F-18]-17 showed specific binding to PDE5 in myocardium of transgenic mice; however [F-18]-11 showed significantly higher PDE5-specific inhibitable binding than [C-11]-12.

  DOI：

  10.1021/acs.jmedchem.6b01666
• 作为产物：
  描述：

  5-(N-叔丁氧羰基氨基)-2-氯吡啶 在 盐酸 、 正丁基锂 、 氯化亚砜 、 四甲基乙二胺 、 三乙胺 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 乙醚 、 乙醇 、 正己烷 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 73.67h， 生成 7-氯-3-[4-(2-羟基乙基)-1-哌嗪基]-1-(2-丙氧乙基)-吡啶并[3,4-b]吡嗪-2(1H)-酮
  参考文献：
  名称：

  Carbon-11 and Fluorine-18 Radiolabeled Pyridopyrazinone Derivatives for Positron Emission Tomography (PET) Imaging of Phosphodiesterase-5 (PDE5)

  摘要：

  The cyclic guanosine monophosphate (cGMP) specific phosphodiesterase type 5 (PDES) plays an important role in various pathologies including pulmonary arterial hypertension and cardiomyopathy. PDES represents an important therapeutic and/or prognostic target, but noninvasive assessment of PDE5 expression is lacking. The purpose of this study was to: develop and evaluate pyridopyrazinone derivatives labeled with carbon-11 or fluorine-18 as PDE5-specific PET tracers. In biodistribution studies, highest PDE5-specific retention was observed for [C-11]-12 and [F-18]-17 in the lungs of wild-type mice and in the myocardium of transgenic mice with cardiomyocyte-specific PDES overexpression at 30 min postinjection. In-vivo dynamic microPET images in rats revealed that both tracers crossed the blood-brain barrier but brain retention was not PDE5-specific. Both [C-11]-.1.2 and [F-18]-17 showed specific binding to PDE5 in myocardium of transgenic mice; however [F-18]-11 showed significantly higher PDE5-specific inhibitable binding than [C-11]-12.

  DOI：

  10.1021/acs.jmedchem.6b01666

文献信息

• Pyridine [3,4-b] Pyrazinones
  申请人：Hughes O. Robert

  公开号：US20070249615A1

  公开（公告）日：2007-10-25

  Compounds and pharmaceutically acceptable salts of the compounds are disclosed, wherein the compounds have the structure of Formula I: wherein R 2 , R 6A , R 6B and R 8 are as defined in the specification. Corresponding pharmaceutical compositions, methods of treatment, synthetic methods, and intermediates are also disclosed.

  本文披露了化合物及其药用可接受的盐，其中化合物具有以下结构的Formula I：其中R2、R6A、R6B和R8如规范中定义。同时还披露了相应的药物组合物、治疗方法、合成方法和中间体。
• Pyridine [3,4-b] pyrazinones
  申请人：Pharmacia & Upjohn Company LLC

  公开号：US07902195B2

  公开（公告）日：2011-03-08

  Compounds and pharmaceutically acceptable salts of the compounds are disclosed, wherein the compounds have the structure of Formula I: wherein R2, R6A, R6B and R8 are as defined in the specification. Corresponding pharmaceutical compositions, methods of treatment, synthetic methods, and intermediates are also disclosed.

  本文披露了化合物及其医药上可接受的盐，其中该化合物具有以下化学结构式（I）：其中R2、R6A、R6B和R8如规范中所定义。此外，还披露了相应的药物组合物、治疗方法、合成方法和中间体。
• Design, Synthesis, and Biological Evaluation of 3-[4-(2-Hydroxyethyl)piperazin-1-yl]-7-(6-methoxypyridin-3-yl)-1-(2-propoxyethyl)pyrido[3,4-<i>b</i>]pyrazin-2(1<i>H</i>)-one, a Potent, Orally Active, Brain Penetrant Inhibitor of Phosphodiesterase 5 (PDE5)
  作者：Robert O. Hughes、D. Joseph Rogier、E. Jon Jacobsen、John K. Walker、Alan MacInnes、Brian R. Bond、Lena L. Zhang、Ying Yu、Yi Zheng、Jeanne M. Rumsey、Jennie L. Walgren、Sandra W. Curtiss、Yvette M. Fobian、Steven E. Heasley、Jerry W. Cubbage、Joseph B. Moon、David L. Brown、Brad A. Acker、Todd M. Maddux、Mike B. Tollefson、Brent V. Mischke、Dafydd R. Owen、John N. Freskos、John M. Molyneaux、Alan G. Benson、Rhadika M. Blevis-Bal

  DOI：10.1021/jm901781q

  日期：2010.3.25

  We recently described a novel series of aminopyridopyrazinones as PDE5 inhibitors. Efforts toward optimization of this series culminated in the identification of 3-[4-(2-hydroxyethyl)piperazin-1-yl]-7-(6-methoxypyridin-3-yl)- 1-(2-propoxyethyl)pyrido[3,4-b]pyrazin-2(1H)-one, which possessed an excellent potency and selectivity profile and demonstrated robust in vivo blood pressure lowering in a spontaneously hypertensive rat (SHR) model. Furthermore, this compound is brain penetrant and will be a useful agent for evaluating the therapeutic potential of central inhibition of PDE5. This compound has recently entered clinical trials.
• J. Med. Chem. 2010, 53, 2656-2660
  作者：

  DOI：——

  日期：——
• PYRIDIN[3,4-B]PYRAZINONES
  申请人：Pfizer Products Inc.

  公开号：EP2013208B1

  公开（公告）日：2011-06-22