N-trifluoroacetyl-4-chloroanthranilic acid | 51984-00-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: N-trifluoroacetyl-4-chloroanthranilic acid
• 英文别名: 4-Chlor-N-trifluoracetylanthranilsaeure；4-chloro-2-(2,2,2-trifluoro-acetylamino)-benzoic acid；4-Chloro-2-[(2,2,2-trifluoroacetyl)amino]benzenecarboxylic acid；4-chloro-2-[(2,2,2-trifluoroacetyl)amino]benzoic acid
• CAS: 51984-00-0
• 化学式: C₉H₅ClF₃NO₃
• 分子量: 267.592
• InChiKey: ZGZSLIZGVJSLCF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  17
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  66.4
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  N-trifluoroacetyl-4-chloroanthranilic acid 在 氯化亚砜 作用下， 以 苯 为溶剂， 反应 12.0h， 生成 7-chloro-2-trifluoromethyl-4H-3,1-benzoxazin-4-one
  参考文献：
  名称：

  吲哚美辛的刚性类似物。

  摘要：

  DOI：

  10.1021/jm00248a005
• 作为产物：
  描述：

  7-chloro-2-trifluoromethyl-4H-3,1-benzoxazin-4-one 以 水 为溶剂， 反应 0.33h， 以91.6%的产率得到N-trifluoroacetyl-4-chloroanthranilic acid
  参考文献：
  名称：

  Development of N-(Functionalized benzoyl)-homocycloleucyl-glycinonitriles as Potent Cathepsin K Inhibitors

  摘要：

  Cathepsin K is a major drug target for osteoporosis and related-bone disorders. Using a combination of virtual combinatorial chemistry, QSAR modeling, and molecular docking studies, a series of cathepsin K inhibitors based on N-(functionalized benzoyl)-homocycloleucyl-glycinonitrile scaffold was developed. In order to avoid previous problems of cathepsin K inhibitors associated with lysosomotropism of compounds with basic character that resulted in off-target effects, a weakly- to nonbasic moiety was incorporated into the P3 position. Compounds 5, 6, and 9 were highly selective for cathepsin K when compared with cathepsins L and S, with the K-i values in the 10-30 nM range. The kinetic studies revealed that the new compounds exhibited reversible tight binding to cathepsin K, while the X-ray structural studies showed covalent and noncovalent binding between the nitrile group and the catalytic cysteine (Cys25) site.

  DOI：

  10.1021/acs.jmedchem.5b00746

文献信息

• Development of <i>N</i>-(Functionalized benzoyl)-homocycloleucyl-glycinonitriles as Potent Cathepsin K Inhibitors
  作者：Jure Borišek、Matej Vizovišek、Piotr Sosnowski、Boris Turk、Dušan Turk、Barbara Mohar、Marjana Novič

  DOI：10.1021/acs.jmedchem.5b00746

  日期：2015.9.10

  Cathepsin K is a major drug target for osteoporosis and related-bone disorders. Using a combination of virtual combinatorial chemistry, QSAR modeling, and molecular docking studies, a series of cathepsin K inhibitors based on N-(functionalized benzoyl)-homocycloleucyl-glycinonitrile scaffold was developed. In order to avoid previous problems of cathepsin K inhibitors associated with lysosomotropism of compounds with basic character that resulted in off-target effects, a weakly- to nonbasic moiety was incorporated into the P3 position. Compounds 5, 6, and 9 were highly selective for cathepsin K when compared with cathepsins L and S, with the K-i values in the 10-30 nM range. The kinetic studies revealed that the new compounds exhibited reversible tight binding to cathepsin K, while the X-ray structural studies showed covalent and noncovalent binding between the nitrile group and the catalytic cysteine (Cys25) site.
• Rigid analogs of indomethacin
  作者：Douglas R. Olson、William J. Wheeler、Jack N. Wells

  DOI：10.1021/jm00248a005

  日期：1974.2