2-[3-chloro-6-(2,2-difluoro-2-pyridin-2-yl-ethyl-tert-Butoxycarbonylamino)-pyridin-2-yl]-acetic acid | 582308-87-0

• 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: 2-[3-chloro-6-(2,2-difluoro-2-pyridin-2-yl-ethyl-tert-Butoxycarbonylamino)-pyridin-2-yl]-acetic acid
• 英文别名: 2-[3-chloro-6-(2,2-difluoro-2-pyridin-2-yl-ethyl-tertButoxycarbonylamino)-pyridin-2-yl]-acetic acid；2-[3-chloro-6-[(2,2-difluoro-2-pyridin-2-ylethyl)-[(2-methylpropan-2-yl)oxycarbonyl]amino]pyridin-2-yl]acetic acid
• CAS: 582308-87-0
• 化学式: C₁₉H₂₀ClF₂N₃O₄
• 分子量: 427.835
• InChiKey: QAXJTTHRBUCZDF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  29
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.37
• 拓扑面积：
  92.6
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  2-[3-chloro-6-(2,2-difluoro-2-pyridin-2-yl-ethyl-tert-Butoxycarbonylamino)-pyridin-2-yl]-acetic acid 在 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 、 三氟乙酸 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 生成 N-[[2-(aminomethyl)phenyl]methyl]-2-[3-chloro-6-[(2,2-difluoro-2-pyridin-2-ylethyl)amino]pyridin-2-yl]acetamide
  参考文献：
  名称：

  P2 pyridine N-oxide thrombin inhibitors: a novel peptidomimetic scaffold

  摘要：

  In this study, we have demonstrated that the critical hydrogen bonding motif of the established 3-aminopyrazinone thrombin inhibitors can be effectively mimicked by a 2-aminopyridine N-oxide. As this peptidomimetic core is more resistant toward oxidative metabolism, it also overcomes the metabolic liability associated with the pyrazinones. An optimization study of the P(1) benzylamide delivered the potent thrombin inhibitor 21 (K(i) = 3.2 nM, 2xaPTT = 360 nM), which exhibited good plasma levels and half-life after oral dosing in the dog (C(max) = 2.6 microM, t(1/2) = 4.5 h).

  DOI：

  10.1016/j.bmcl.2005.03.110
• 作为产物：
  描述：

  6-甲基吡啶-2-氨基甲酸叔丁酯 在 lithium hydroxide 、 N-氯代丁二酰亚胺 、 DCE 、 sodium hydride 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 生成 2-[3-chloro-6-(2,2-difluoro-2-pyridin-2-yl-ethyl-tert-Butoxycarbonylamino)-pyridin-2-yl]-acetic acid
  参考文献：
  名称：

  P2 pyridine N-oxide thrombin inhibitors: a novel peptidomimetic scaffold

  摘要：

  In this study, we have demonstrated that the critical hydrogen bonding motif of the established 3-aminopyrazinone thrombin inhibitors can be effectively mimicked by a 2-aminopyridine N-oxide. As this peptidomimetic core is more resistant toward oxidative metabolism, it also overcomes the metabolic liability associated with the pyrazinones. An optimization study of the P(1) benzylamide delivered the potent thrombin inhibitor 21 (K(i) = 3.2 nM, 2xaPTT = 360 nM), which exhibited good plasma levels and half-life after oral dosing in the dog (C(max) = 2.6 microM, t(1/2) = 4.5 h).

  DOI：

  10.1016/j.bmcl.2005.03.110

文献信息

• Thrombin inhibitors
  申请人：——

  公开号：US20030158218A1

  公开（公告）日：2003-08-21

  Compounds of the invention are useful in inhibiting thrombin and associated thrombotic occlusions having the following structure: 1 wherein R 1 is, for example, hydrogen, Cl, or cyano, and R 2 is, for example, hydrogen, 2

  本发明的化合物在抑制凝血酶及相关血栓闭塞方面具有以下结构的有用： 1 其中R 1 例如是氢、氯或氰基，而R 2 例如是氢、 2
• P2 pyridine N-oxide thrombin inhibitors: a novel peptidomimetic scaffold
  作者：Philippe G. Nantermet、Christopher S. Burgey、Kyle A. Robinson、Janetta M. Pellicore、Christina L. Newton、James Z. Deng、Harold G. Selnick、S. Dale Lewis、Bobby J. Lucas、Julie A. Krueger、Cynthia Miller-Stein、Rebecca B. White、Bradley Wong、Daniel R. McMasters、Audrey A. Wallace、Joseph J. Lynch、Youwei Yan、Zhongguo Chen、Lawrence Kuo、Stephen J. Gardell、Jules A. Shafer、Joseph P. Vacca、Terry A. Lyle

  DOI：10.1016/j.bmcl.2005.03.110

  日期：2005.6

  In this study, we have demonstrated that the critical hydrogen bonding motif of the established 3-aminopyrazinone thrombin inhibitors can be effectively mimicked by a 2-aminopyridine N-oxide. As this peptidomimetic core is more resistant toward oxidative metabolism, it also overcomes the metabolic liability associated with the pyrazinones. An optimization study of the P(1) benzylamide delivered the potent thrombin inhibitor 21 (K(i) = 3.2 nM, 2xaPTT = 360 nM), which exhibited good plasma levels and half-life after oral dosing in the dog (C(max) = 2.6 microM, t(1/2) = 4.5 h).