[5-chloro-2-(4-chlorophenyl)indol-3-yl]glyoxylyl chloride | 681481-90-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: [5-chloro-2-(4-chlorophenyl)indol-3-yl]glyoxylyl chloride
• CAS: 681481-90-3
• 化学式: C₁₆H₈Cl₃NO₂
• 分子量: 352.604
• InChiKey: KHNMUHLVDFARBK-UHFFFAOYSA-N

物化性质

• 沸点：
  577.8±60.0 °C(Predicted)
• 密度：
  1.525±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.09
• 重原子数：
  22.0
• 可旋转键数：
  3.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  49.93
• 氢给体数：
  1.0
• 氢受体数：
  2.0

反应信息

• 作为反应物：
  描述：

  甲基丁胺 、 [5-chloro-2-(4-chlorophenyl)indol-3-yl]glyoxylyl chloride 在 三乙胺 作用下， 以 甲苯 为溶剂， 以49%的产率得到N-butyl-2-(5-chloro-2-(4-chlorophenyl)-1H-indol-3-yl)-N-methyl-2-oxoacetamide
  参考文献：
  名称：

  Anxiolytic-like Effects of N,N-Dialkyl-2-phenylindol-3-ylglyoxylamides by Modulation of Translocator Protein Promoting Neurosteroid Biosynthesis

  摘要：

  Novel N,N-disubstituted indol-3-ylglyoxylamides (1-56), bearing different combinations of substituents R-1-R-5, were synthesized and evaluated as ligands of the translocator protein (TSPO), the 18 kDa protein representing the minimal functional unit of the "peripheral-type benzodiazepine receptor" (PBR). Most of the new compounds showed a nanomolar/subnanomolar affinity for TSPO and stimulated steroid biosynthesis in rat C6 glioma cells with a potency similar to or higher than that of classic TSPO ligands such as PK 11195. Moreover, when evaluated in vivo by means of the elevated-plus-maze (EPM) paradigm in the rat, compound 32. the best-performing derivative in terms of TSPO affinity and pregnenolone production, showed clear anxiolytic effects. The results of this study suggested that the novel N, N-di substituted indol-3y1glyoxylani ides may represent a promising class of compounds potentially suited for the treatment of anxiety disorders.

  DOI：

  10.1021/jm8003224
• 作为产物：
  描述：

  4-氯-N-(4-氯-2-甲基苯基)苯甲酰胺 在 正丁基锂 作用下， 以 四氢呋喃 、 乙醚 、 正己烷 为溶剂， 生成 [5-chloro-2-(4-chlorophenyl)indol-3-yl]glyoxylyl chloride
  参考文献：
  名称：

  N，N-二烷基-2-苯基吲哚-3-基乙氧基叠氮化物。在外周苯并二氮杂receptor受体上的一类新的有效和选择性配体。

  摘要：

  我们报告了一系列N，N-二烷基-2-苯基吲哚-3-基乙醛酰胺衍生物III（设计为2-苯基吲哚-构象约束类似物）的外围（PBR）和中心苯并二氮杂receptor受体的合成和亲和力数据。 3-乙酰胺II，例如FGIN-1-27。大多数新化合物对PBR表现出高特异性和亲和性，K（i）在纳摩尔至亚纳摩尔范围内。最有效的配体（4-7、9、13-27）刺激了大鼠C6胶质瘤细胞中类固醇的生物合成，其功效与经典配体相似或更高。讨论了这类新型化合物的SAR。

  DOI：

  10.1021/jm030973k

文献信息

• Unbinding of Translocator Protein 18 kDa (TSPO) Ligands: From in Vitro Residence Time to in Vivo Efficacy via in Silico Simulations
  作者：Agostino Bruno、Elisabetta Barresi、Nicola Simola、Eleonora Da Pozzo、Barbara Costa、Ettore Novellino、Federico Da Settimo、Claudia Martini、Sabrina Taliani、Sandro Cosconati

  DOI：10.1021/acschemneuro.9b00300

  日期：2019.8.21

  Translocator protein 18 kDa (TSPO) is a validated pharmacological target for the development of new treatments for neurological disorders. N,N-Dialkyl-2-phenyl-indol-3-ylglyoxylamides (PIGAs) are effective TSPO modulators and potentially useful therapeutics for the treatment of anxiety, central nervous system pathologies featuring astrocyte loss, and inflammatory-based neuropathologies. For this class of compounds, no correlation exists between the TSPO binding affinity and the corresponding functional efficacy. Rather, their biological effectiveness correlates with the kinetics of the unbinding events and more specifically with the residence time (RT). So far, the structural reasons for the different recorded RT of congeneric PIGAs remain elusive. Here, to understand the different kinetics of PIGAs, their unbinding paths were studied by employing enhanced-sampling molecular dynamics simulations. Results of these studies revealed how subtle structural differences between PIGAs have a substantial effect on the unbinding energetics. In particular, during the egress from the TSPO binding site, slow-dissociating PIGAs find tight interactions with the protein LP1 region thereby determining a long RT. Further support to these findings was achieved by in vivo studies, which demonstrated how the anxiolytic effect observed for the inspected PIGAs correlated with their RT to TSPO.