3-(4-(2-hydroxyethyl)piperazin-1-yl)-7-(6-methoxypyridin-3-yl)-1-(2-propoxyethyl)pyrido[3,4-b]pyrazin-2(1H)-one | 954138-07-9

• 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: 3-(4-(2-hydroxyethyl)piperazin-1-yl)-7-(6-methoxypyridin-3-yl)-1-(2-propoxyethyl)pyrido[3,4-b]pyrazin-2(1H)-one
• 英文别名: 3-[4-(2-hydroxyethyl)piperazin-1-yl]-7-(6-methoxypyridin-3-yl)-1-(2-propoxyethyl)-1H,2H-pyrido[3,4-b]pyrazin-2-one；3-[4-(2-hydroxyethyl)piperazin-1-yl]-7-(6-methoxypyridin-3-yl)-1-(2-propoxyethyl)pyrido[3,4-b]pyrazin-2-one
• CAS: 954138-07-9
• 化学式: C₂₄H₃₂N₆O₄
• 分子量: 468.556
• InChiKey: MNLNAGRCHNMKKJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  34
• 可旋转键数：
  10
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  104
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  3-(4-(2-hydroxyethyl)piperazin-1-yl)-7-(6-methoxypyridin-3-yl)-1-(2-propoxyethyl)pyrido[3,4-b]pyrazin-2(1H)-one 、 对甲苯磺酰氯 在 三甲胺盐酸盐 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 16.0h， 以38%的产率得到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：

  3,7-dichloro-1-(2-propoxyethyl)pyrido[3,4-b]pyrazin-2(1H)-one 在 四(三苯基膦)钯 、 三乙胺 作用下， 以 四氢呋喃 、 1,4-二氧六环 为溶剂， 反应 20.08h， 生成 3-(4-(2-hydroxyethyl)piperazin-1-yl)-7-(6-methoxypyridin-3-yl)-1-(2-propoxyethyl)pyrido[3,4-b]pyrazin-2(1H)-one
  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。
• Compositions to improve the therapeutic benefit of bisantrene and analogs and derivatives thereof
  申请人：Race Oncology Ltd.

  公开号：US10548876B2

  公开（公告）日：2020-02-04

  The present invention describes methods and compositions for improving the therapeutic efficacy of therapeutic agents previously limited by suboptimal therapeutic performance by either improving efficacy as monotherapy or reducing side effects. Such methods and compositions are particularly applicable to bisantrene or derivatives, analogs, or prodrugs thereof.

  本发明描述了通过提高单一疗法的疗效或减少副作用来改善以前因治疗效果不理想而受到限制的治疗剂的疗效的方法和组合物。这些方法和组合物尤其适用于双蒽或其衍生物、类似物或原药。
• Combinatorial methods to improve the therapeutic benefit of bisantrene and analogs and derivatives thereof
  申请人：Race Oncology Ltd.

  公开号：US11147800B2

  公开（公告）日：2021-10-19

  The present invention describes methods and compositions for improving the therapeutic efficacy of therapeutic agents previously limited by suboptimal therapeutic performance by either improving efficacy as monotherapy or reducing side effects. Such methods and compositions are particularly applicable to bisantrene or derivatives, analogs, or prodrugs thereof.

  本发明描述了通过提高单一疗法的疗效或减少副作用来改善以前因治疗效果不理想而受到限制的治疗剂的疗效的方法和组合物。这些方法和组合物尤其适用于双蒽或其衍生物、类似物或原药。
• J. Med. Chem. 2010, 53, 2656-2660
  作者：

  DOI：——

  日期：——