tert-butyl N-(5-chloro-6-methyl-2-pyridyl)carbamate | 582308-82-5

• 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: tert-butyl N-(5-chloro-6-methyl-2-pyridyl)carbamate
• 英文别名: (5-Chloro-6-methyl-pyridin-2-yl)-carbamic acid tert-butyl ester；tert-Butyl (5-chloro-6-methylpyridin-2-yl)carbamate；tert-butyl N-(5-chloro-6-methylpyridin-2-yl)carbamate
• CAS: 582308-82-5
• 化学式: C₁₁H₁₅ClN₂O₂
• 分子量: 242.705
• InChiKey: SBCVWGKVTJBITE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  16
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  51.2
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  tert-butyl N-(5-chloro-6-methyl-2-pyridyl)carbamate 在 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 {6-[tert-Butoxycarbonyl-(2,2-difluoro-2-pyridin-2-yl-ethyl)-amino]-3-chloro-pyridin-2-yl}-acetic acid ethyl ester
  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 N-氯代丁二酰亚胺 、 DCE 作用下， 生成 tert-butyl N-(5-chloro-6-methyl-2-pyridyl)carbamate
  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
• Discovery and Characterization of Selective, First-in-Class Inhibitors of Citron Kinase
  作者：Joshua J. Maw、Jesse A. Coker、Tarun Arya、Christopher M. Goins、Dhiraj Sonawane、Sang Hoon Han、Matthew G. Rees、Melissa M. Ronan、Jennifer A. Roth、Nancy S. Wang、Hannelore V. Heemers、Jonathan D. Macdonald、Shaun R. Stauffer

  DOI：10.1021/acs.jmedchem.3c01807

  日期：2024.2.22

  Citron kinase (CITK) is an AGC-family serine/threonine kinase that regulates cytokinesis. Despite knockdown experiments implicating CITK as an anticancer target, no selective CITK inhibitors exist. We transformed a previously reported kinase inhibitor with weak off-target CITK activity into a first-in-class CITK chemical probe, C3TD879. C3TD879 is a Type I kinase inhibitor which potently inhibits CITK

  柚子激酶 （CITK） 是一种调节胞质分裂的 AGC 家族丝氨酸/苏氨酸激酶。尽管敲低实验表明 CITK 是抗癌靶点，但不存在选择性 CITK 抑制剂。我们将先前报道的具有弱脱靶 CITK 活性的激酶抑制剂转化为同类首创的 CITK 化学探针 C3TD879。C3TD879 是一种 I 型激酶抑制剂，可有效抑制 CITK 催化活性 （生化 IC50 = 12 nM），直接与细胞中的全长人 CITK 结合 （NanoBRET Kd < 10 nM），并显示出良好的 DMPK 特性用于体内评估。我们对 CITK 设计了极好的选择性（>17 倍于其他 373 种人类激酶），使 C3TD879 成为第一个适合研究 CITK 复杂生物学的化学探针。我们的小分子 CITK 抑制剂无法表型复制 CITK 敲低在细胞增殖、细胞周期进程或胞质分裂测定中的作用，提供了初步证据，证明 CITK 的结构作用可能比其激酶活性更重要。
• 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).