2-[3-(trifluoromethyl)phenyl]-1,3-thiazole-4-carboxylic Acid | 115311-32-5

• 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: 2-[3-(trifluoromethyl)phenyl]-1,3-thiazole-4-carboxylic Acid
• CAS: 115311-32-5
• 化学式: C₁₁H₆F₃NO₂S
• mdl: MFCD00142039
• 分子量: 273.235
• InChiKey: OMMDRDBAUFWKPT-UHFFFAOYSA-N

物化性质

• 熔点：
  200-202°C

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  78.4
• 氢给体数：
  1
• 氢受体数：
  7

安全信息

• 危险等级：
  IRRITANT

反应信息

• 作为反应物：
  描述：

  2-[3-(trifluoromethyl)phenyl]-1,3-thiazole-4-carboxylic Acid 在 过氧乙酸 、 碳酸氢钠 作用下， 以 四氢呋喃 、 水 为溶剂， 生成 4-(5-methylsulfonyl-1H-1,2,4-triazol-3-yl)-2-[3-(trifluoromethyl)phenyl]-1,3-thiazole
  参考文献：
  名称：

  1,2,4-Triazolsulfone: A novel isosteric replacement of acylsulfonamides in the context of Na V 1.7 inhibition

  摘要：

  Recently, the identification of several classes of aryl sulfonamides and acyl sulfonamides that potently inhibit Na(v)1.7 and demonstrate high levels of selectivity over other Na-v isoforms have been reported. The fully ionizable nature of these inhibitors has been shown to be an important part of the pharmacophore for the observed potency and isoform selectivity. The requirement of this functionality, however, has presented challenges associated with optimization toward inhibitors with drug-like properties and minimal off-target activity. In an effort to obviate these challenges, we set out to develop an orally bioavailable, selective Na(v)1.7 inhibitor, lacking these acidic functional groups. Herein, we report the discovery of a novel series of inhibitors wherein a triazolesulfone has been designed to serve as a bioisostere for the acyl sulfonamide. This work culminated in the delivery of a potent series of inhibitors which demonstrated good levels of selectivity over Na v 1.5 and favorable pharmacokinetics in rodents. (C) 2018 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2018.04.035

文献信息

• Discovery of Novel Small-Molecule Inhibitors of NF-κB Signaling with Antiinflammatory and Anticancer Properties
  作者：Lei Zhang、Lei Shi、Shafer Myers Soars、Joshua Kamps、Hang Yin

  DOI：10.1021/acs.jmedchem.7b01557

  日期：2018.7.26

  activation contributes to the pathogenesis of numerous diseases. Small-molecule inhibitors of NF-κB signaling have significant therapeutic potential especially in treating inflammatory diseases and cancers. In this study, we performed a cell-based high-throughput screening to discover novel agents capable of inhibiting NF-κB signaling. On the basis of two hit scaffolds from the screening, we synthesized

  NF-κB过度活化导致多种疾病的发病机理。NF-κB信号的小分子抑制剂具有显着的治疗潜力，尤其是在治疗炎症性疾病和癌症方面。在这项研究中，我们进行了基于细胞的高通量筛选，以发现能够抑制NF-κB信号传导的新型药物。在筛选的两个命中支架的基础上，我们合成了69种衍生物，以优化抑制NF-κB活化的能力，从而成功发现了最有效的化合物Z9j，其抑制活性增强了170倍以上。初步的力学研究表明Z9j通过抑制Src / Syk，PI3K / Akt和IKK /IκB途径来抑制NF-κB信号传导。该新型化合物还显示出抗炎和抗癌活性，使其作为治疗炎性疾病和癌症的潜在多功能剂得以进一步发展。
• Methods for identifying compounds that modulate enzymatic activity
  申请人：——

  公开号：US20040005632A1

  公开（公告）日：2004-01-08

  The present invention relates to the use of “tethering” to identify compounds that modulate enzymatic activity.

  本发明涉及利用 "系链 "来鉴定调节酶活性的化合物。
• Design, synthesis, and evaluation of thiazolecarboxamide derivatives as stimulator of interferon gene inhibitors
  作者：Zechen Jin、Yan Zhang、Xin Luo、Meiyu Geng、Wenhu Duan、Zuoquan Xie、Hefeng Zhang

  DOI：10.1007/s11030-024-10860-6

  日期：2025.2

  Stimulator of interferon gene (STING) plays critical roles in the cytoplasmic DNA-sensing pathway and in the induction of inflammatory response. Aberrant cytoplasmic DNA accumulation and STING activation are implicated in numerous inflammatory and autoimmune diseases. Here, we reported the discovery of a series of thiazolecarboxamide-based STING inhibitors through a molecular planarity/symmetry disruption

  干扰素基因刺激物 (STING) 在细胞质 DNA 传感途径和炎症反应的诱导中发挥着关键作用。异常的细胞质 DNA 积累和 STING 激活与许多炎症和自身免疫性疾病有关。在这里，我们报告了通过分子平面性/对称性破坏策略发现了一系列基于噻唑甲酰胺的 STING 抑制剂。特权化合物15b显着抑制人类和小鼠细胞中的 STING 信号传导并抑制免疫炎症细胞因子水平。体内实验表明， 15b可有效改善 MSA-2 刺激的小鼠和Trex1 -D18N 小鼠中的免疫炎症细胞因子上调。此外，化合物15b在抑制干扰素刺激基因 15 (ISG15) 方面表现出增强的功效，干扰素刺激基因 15 是 STING 的关键正反馈调节因子。总体而言，化合物15b值得进一步开发用于治疗 STING 相关炎症和自身免疫性疾病。  图形概要
• N-tetrazolyl thiazolecarboxamide derivatives and their use
  申请人：SAWAI PHARMACEUTICAL CO., LTD.

  公开号：EP0262873B1

  公开（公告）日：1991-08-21
• YOSHINAGA, JUNJI;SHOYAKI, TAKESHI;KAKITA, TAKAO;OZEKI, HIROMI;SUGIMOTO, N+
  作者：YOSHINAGA, JUNJI、SHOYAKI, TAKESHI、KAKITA, TAKAO、OZEKI, HIROMI、SUGIMOTO, N+

  DOI：——

  日期：——