4-isothiocyanatomethyl-benzonitrile | 3694-48-2

• 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: 4-isothiocyanatomethyl-benzonitrile
• 英文别名: 4-Isothiocyanatomethyl-benzonitril；4-(Isothiocyanatomethyl)benzonitrile
• CAS: 3694-48-2
• 化学式: C₉H₆N₂S
• 分子量: 174.226
• InChiKey: TZQWCCPNIOIMFE-UHFFFAOYSA-N

物化性质

• 熔点：
  73-73.5 °C
• 沸点：
  128-130 °C(Press: 0.035 Torr)
• 密度：
  1.2126 (rough estimate)

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  12
• 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：
  68.2
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-isothiocyanatomethyl-benzonitrile 在 一水合肼 、 溶剂黄146 作用下， 以 乙醚 、 N,N-二甲基甲酰胺 为溶剂， 反应 24.0h， 生成 N-(4-cyanobenzyl)-5-(benzo[d]imidazol-2(3H)-one)-6H-1,3,4-thiadiazin-2-amine
  参考文献：
  名称：

  Novel selective thiadiazine DYRK1A inhibitor lead scaffold with human pancreatic β-cell proliferation activity

  摘要：

  The Dual-Specificity Tyrosine Phosphorylation-Regulated Kinase 1A (DYRK1A) is an enzyme that has been implicated as an important drug target in various therapeutic areas, including neurological disorders (Down syndrome, Alzheimer's disease), oncology, and diabetes (pancreatic beta-cell expansion). Current small molecule DYRK1A inhibitors are ATP-competitive inhibitors that bind to the kinase in an active conformation. As a result, these inhibitors are promiscuous, resulting in pharmacological side effects that limit their therapeutic applications. None are in clinical trials at this time. In order to identify a new DYRK1A inhibitor scaffold, we constructed a homology model of DYRK1A in an inactive, DFG-out conformation. Virtual screening of 2.2 million lead-like compounds from the ZINC database, followed by in vitro testing of selected 68 compounds revealed 8 hits representing 5 different chemical classes. We chose to focus on one of the hits from the computational screen, thiadiazine I which was found to inhibit DYRK1A with IC50 of 9.41 mu m (K-d = 7.3 mu M). Optimization of the hit compound 1, using structure-activity relationship (SAR) analysis and in vitro testing led to the identification of potent thiadiazine analogs with significantly improved binding as compared to the initial hit (K-d = 71-185 nM). Compound 3-5 induced human beta-cell proliferation at 5 mu M while showing selectivity for DYRK1A over DYRK1B and DYRK2 at 10 mu M. This newly developed DYRK1A inhibitor scaffold with unique kinase selectivity profiles has potential to be further optimized as novel therapeutics for diabetes. (C) 2018 Published by Elsevier Masson SAS.

  DOI：

  10.1016/j.ejmech.2018.08.007
• 作为产物：
  描述：

  4-cyanobenzyl thiocyanate 在 9,10-二联苯蒽 作用下， 以 苯 为溶剂， 生成 4-isothiocyanatomethyl-benzonitrile
  参考文献：
  名称：

  电子转移引起的硫氰酸酯重排为异硫氰酸酯

  摘要：

  在9,10-二苯基蒽（DPA）敏化作用下，具有吸电子基团（1a，1b）和9-芴基硫氰酸酯（1e）的硫氰酸苄酯重排为相应的异硫氰酸酯（2）。重排将通过光诱导的电子转移产生的阴离子基团1中的碳硫键断裂而进行，然后将电子反向转移至DPA ·+并重组所得的基团或离子对。

  DOI：

  10.1016/s0040-4039(99)02063-8

文献信息

• Substitution Reaction of Organic Halide by Trimethylsilyl Isothiocyanate: Formation of Thiocyanate and Its Rearrangement to Isothiocyanate
  作者：Kozaburo Nishiyama、Makoto Oba

  DOI：10.1246/bcsj.60.2692

  日期：1987.7

  The reaction of organic halide with trimethylsilyl isothiocyanate (TMSTC) gave thiocyanate 1 and its isomerized isothiocyanate 2. Details of the substituion and the isomerization reactions were examined.

  有机卤化物与异硫氰酸三甲基甲硅烷基酯 (TMSTC) 的反应得到硫氰酸酯 1 及其异构化的异硫氰酸酯 2。对取代和异构化反应的细节进行了检查。
• Synthesis and Evaluation of Functionalized Aryl and Biaryl Isothiocyanates against Human MCF‐7 Cells
  作者：Claire C. Fanta、Kaitlyn J. Tlusty、Sarah E. Pauley、Amanda L. Johnson、Genevieve A. Benjamin、Taylor K. Yseth、Michaela M. Bunde、Paul T. Pierce、Shirley Wang、Peter F. Vitiello、Jared R. Mays

  DOI：10.1002/cmdc.202200250

  日期：2022.7.19

  properties of isothiocyanate 160 against MCF-7 cells after 24 h and 72 h incubation are shown. The plots depict data acquired via antiproliferation and ARE-induction assays; the area below ARE-induction data is shaded to improve clarity (t=24 h, light gray). The results of this study led to the identification of several key structure-activity relationships, as well as lead isothiocyanates demonstrating

  显示了孵育 24 小时和 72 小时后异硫氰酸酯160对 MCF-7 细胞的剂量反应抗癌特性。这些图描绘了通过抗增殖和 ARE 诱导测定获得的数据；ARE 感应数据下方的区域带有阴影以提高清晰度（t=24 小时，浅灰色）。这项研究的结果确定了几种关键的结构-活性关系，以及异硫氰酸铅表现出有效的抗增殖特性。
• SWEETNESS RECEPTOR ANTAGONIST
  申请人：Ajinomoto Co., Inc.

  公开号：EP3162366A1

  公开（公告）日：2017-05-03

  The present invention aims to provide a sweetness receptor antagonist useful for the prophylaxis or treatment of metabolic syndrome, diabetes, obesity and the like. A sweetness receptor antagonist containing a compound represented by the formula (I) wherein each symbol is as described in the DESCRIPTION, or a salt thereof.

  本发明旨在提供一种甜味受体拮抗剂，用于预防或治疗代谢综合征、糖尿病、肥胖症等。甜味受体拮抗剂含有由式（I）代表的化合物 其中各符号如说明书所述，或其盐。
• Bacteriostats. II.¹ The Chemical and Bacteriostatic Properties of Isothiocyanates and their Derivatives
  作者：A. F. McKay、D. L. Garmaise、R. Gaudry、H. A. Baker、G. Y. Paris、R. W. Kay、G. E. Just、R. Schwartz

  DOI：10.1021/ja01525a057

  日期：1959.8
• NISHIYAMA, KOZABURO;OBA, MAKOTO, BULL. CHEM. SOC. JAP., 60,(1987) N 7, 2692-2694
  作者：NISHIYAMA, KOZABURO、OBA, MAKOTO

  DOI：——

  日期：——