2-{6-Chloro-3-[2,2-difluoro-2-(1-oxy-pyridin-2-yl)-ethylamino]-2-oxo-2H-pyrazin-1-yl}-N-(3-methoxy-benzyl)-acetamide

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 2-{6-Chloro-3-[2,2-difluoro-2-(1-oxy-pyridin-2-yl)-ethylamino]-2-oxo-2H-pyrazin-1-yl}-N-(3-methoxy-benzyl)-acetamide
• 英文别名: 2-[6-chloro-3-[[2,2-difluoro-2-(1-oxidopyridin-1-ium-2-yl)ethyl]amino]-2-oxopyrazin-1-yl]-N-[(3-methoxyphenyl)methyl]acetamide
• 化学式: C₂₁H₂₀ClF₂N₅O₄
• 分子量: 479.871
• InChiKey: AOGHMNBYHDJVHQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  33
• 可旋转键数：
  9
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  109
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  2-(2-azido-1,1-difluoro-ethyl)-pyridine N-oxide 在 N-甲基吗啉 、 氢氧化钾 、 N-氯代丁二酰亚胺 、 N-羟基-7-氮杂苯并三氮唑 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 、 三乙胺 、 三苯基膦 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 1,2-二氯乙烷 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 生成 2-{6-Chloro-3-[2,2-difluoro-2-(1-oxy-pyridin-2-yl)-ethylamino]-2-oxo-2H-pyrazin-1-yl}-N-(3-methoxy-benzyl)-acetamide
  参考文献：
  名称：

  Pharmacokinetic optimization of 3-amino-6-chloropyrazinone acetamide thrombin inhibitors. implementation of P3 pyridine N-Oxides to deliver an orally bioavailable series containing P1 N-Benzylamides

  摘要：

  In this manuscript we demonstrate that a modification principally directed toward the improvement of the aqueous solubility (i.e., introduction a P3 pyridine N-oxide) of the previous lead compound afforded a new series of potent orally bioavailable PI N-benzylamide thrombin inhibitors. An expedited investigation of the PI SAR with respect to oral bioavailability, plasma half-life, and human liver microsome stability revealed 5 as the best candidate for advanced evaluation. (C) 2003 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(03)00099-4

文献信息

• Pharmacokinetic optimization of 3-amino-6-chloropyrazinone acetamide thrombin inhibitors. implementation of P3 pyridine N-Oxides to deliver an orally bioavailable series containing P1 N-Benzylamides
  作者：Christopher S. Burgey、Kyle A. Robinson、Terry A. Lyle、Philippe G. Nantermet、Harold G. Selnick、Richard C.A. Isaacs、S.Dale Lewis、Bobby J. Lucas、Julie A. Krueger、Rominder Singh、Cynthia Miller-Stein、Rebecca B. White、Bradley Wong、Elizabeth A. Lyle、Maria T. Stranieri、Jacquelynn J. Cook、Daniel R. McMasters、Janetta M. Pellicore、Swati Pal、Audrey A. Wallace、Franklin C. Clayton、Dennis Bohn、Denise C. Welsh、Joseph J. Lynch、Youwei Yan、Zhongguo Chen、Lawrence Kuo、Stephen J. Gardell、Jules A. Shafer、Joseph P. Vacca

  DOI：10.1016/s0960-894x(03)00099-4

  日期：2003.4

  In this manuscript we demonstrate that a modification principally directed toward the improvement of the aqueous solubility (i.e., introduction a P3 pyridine N-oxide) of the previous lead compound afforded a new series of potent orally bioavailable PI N-benzylamide thrombin inhibitors. An expedited investigation of the PI SAR with respect to oral bioavailability, plasma half-life, and human liver microsome stability revealed 5 as the best candidate for advanced evaluation. (C) 2003 Elsevier Science Ltd. All rights reserved.