N′-hydroxy-2-(4-(trifluoromethyl)phenyl)-acetimidamide | 176860-56-3

• 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′-hydroxy-2-(4-(trifluoromethyl)phenyl)-acetimidamide
• 英文别名: Benzeneethanimidamide, N-hydroxy-4-(trifluoromethyl)-；N'-hydroxy-2-[4-(trifluoromethyl)phenyl]ethanimidamide
• CAS: 176860-56-3
• 化学式: C₉H₉F₃N₂O
• 分子量: 218.178
• InChiKey: QPSFNZJGLHDENP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  15
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  58.6
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  N′-hydroxy-2-(4-(trifluoromethyl)phenyl)-acetimidamide 在 吡啶 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 15.5h， 生成 {2-[3-(4-Trifluoromethyl-benzyl)-[1,2,4]oxadiazol-5-yl]-ethyl}-carbamic acid tert-butyl ester
  参考文献：
  名称：

  Discovery of Potent and Selective SH2 Inhibitors of the Tyrosine Kinase ZAP-70

  摘要：

  A series of 1,2,4-oxadiazole analogues has been shown to be potent and selective SH2 inhibitors of the tyrosine kinase ZAP-70, a potential therapeutic target for immune suppression. These compounds typically are 200-400-fold more potent than the native, monophosphorylated tetrapeptide sequences. When compared with the high-affinity xi-1-ITAM peptide (Ac-NQL-pYNELNLGRREE-pYDVLD-NH2, wherein pY refers to phosphotyrosine) some of the best 1,2,4-oxadiazole analogues are approximately 1 order of magnitude less active. This series of compounds displays an unprecedented level of selectivity over the closely related tyrosine kinase Syk, as well as other SH2-containing proteins such as Src and Grb2. Gel shift studies using a protein construct consisting only of C-terminal ZAP-70 SH2 demonstrate that these compounds can effectively engage this particular SH2 domain.

  DOI：

  10.1021/jm990229t
• 作为产物：
  描述：

  对三氟甲基苯乙腈 在 盐酸羟胺 、 碳酸氢钠 作用下， 以 乙醇 、 水 为溶剂， 生成 N′-hydroxy-2-(4-(trifluoromethyl)phenyl)-acetimidamide
  参考文献：
  名称：

  I2-催化串联 sp3 C-H 氧化和芳基甲基酮与偕胺肟成环合成 5-芳酰基-1,2,4-恶二唑

  摘要：

  开发了一种无金属、碘催化的方案，用于使用芳基甲基酮和偕胺肟构建具有生物学意义的 5-芳酰基 1,2,4-恶二唑支架。该策略可产生结构多样的 5-芳酰基 1,2,4-恶二唑，产率良好至优异，底物范围广泛，包括药物衍生底物。该反应通过碘/DMSO 介导的芳基甲基酮氧化进行，随后形成亚胺并随后环化以产生所需产物。此外，该方案还成功生产了 ataluren 和 tioxazafen 的羰基类似物，并促进了一些有趣的后期转化。

  DOI：

  10.1039/d4ob01221f

文献信息

• PURINONE DERIVATIVES AS HM74A AGONISTS
  申请人：Zheng Changsheng

  公开号：US20080045554A1

  公开（公告）日：2008-02-21

  The present invention relates to purinone derivatives which are agonists of the HM74a receptor. Further provided are compositions and methods of using the compounds herein, and their pharmaceutically acceptable salts for the treatment of disease.

  本发明涉及嘌呤酮衍生物，其为HM74a受体激动剂。此外，还提供了本文化合物的组合物和使用方法，以及它们的药用盐，用于治疗疾病。
• [EN] QUINAZOLINONE-TYPE COMPOUNDS AS CRTH2 ANTAGONISTS<br/>[FR] COMPOSÉS DE TYPE QUINAZOLINONE CONVENANT COMME ANTAGONISTES DE CRTH2
  申请人：MERCK SHARP & DOHME

  公开号：WO2012051036A1

  公开（公告）日：2012-04-19

  This application provides for compounds of the formula Formula I or a pharmaceutically acceptable salt thereof, wherein the individual variables are defined herein, as well as processes to prepare these compounds, pharmaceutical compositions comprising the same and their use in treating disease state associated with the CRTH2 receptor.

  该应用程序提供了Formula I的化合物或其药用可接受盐，其中个别变量在此定义，以及制备这些化合物的过程，包括相同的药物组成和它们在治疗与CRTH2受体相关的疾病状态中的用途。
• [EN] CARBOXY DERIVATIVES WITH ANTIINFLAMMATORY PROPERTIES<br/>[FR] DÉRIVÉS CARBOXY PRÉSENTANT DES PROPRIÉTÉS ANTI-INFLAMMATOIRES
  申请人：SITRYX THERAPEUTICS LTD

  公开号：WO2021130492A1

  公开（公告）日：2021-07-01

  The invention relates to compounds of formula (I) and to their use in treating or preventing an inflammatory disease or a disease associated with an undesirable immune response: (I) wherein, RA1, RA2, RC and RD are as defined herein.

  这项发明涉及式(I)的化合物及其在治疗或预防炎症性疾病或与不良免疫反应相关的疾病中的应用：(I)其中，RA1、RA2、RC和RD如本文所定义。
• Synergism of a Novel 1,2,4-oxadiazole-containing Derivative with Oxacillin against Methicillin-Resistant Staphylococcus aureus
  作者：Elisabetta Buommino、Simona De Marino、Martina Sciarretta、Marialuisa Piccolo、Carmen Festa、Maria Valeria D’Auria

  DOI：10.3390/antibiotics10101258

  日期：——

  Staphylococcusaureus is an important opportunistic pathogen that causes many infections in humans and animals. The inappropriate use of antibiotics has favored the diffusion of methicillin-resistant S. aureus (MRSA), nullifying the efforts undertaken in the discovery of antimicrobial agents. Oxadiazole heterocycles represent privileged scaffolds for the development of new drugs because of their unique bioisosteric properties, easy synthesis, and therapeutic potential. A vast number of oxadiazole-containing derivatives have been discovered as potent antibacterial agents against multidrug-resistant MRSA strains. Here, we investigate the ability of a new library of oxadiazoles to contrast the growth of Gram-positive and Gram-negative strains. The strongest antimicrobial activity was obtained with compounds 3 (4 µM) and 12 (2 µM). Compound 12, selected for further evaluation, was found to be noncytotoxic on the HaCaT cell line up to 25 µM, bactericidal, and was able to improve the activity of oxacillin against the MRSA. The highest synergistic interaction was obtained with the combination values of 0.78 μM for compound 12, and 0.06 μg/mL for oxacillin. The FIC index value of 0.396 confirms the synergistic effect of compound 12 and oxacillin. MRSA treatment with compound 12 reduced the expression of genes included in the mec operon. In conclusion, 12 inhibited the growth of the MRSA and restored the activity of oxacillin, thus resulting in a promising compound in the treatment of MRSA infection.

  金黄色葡萄球菌是一种重要的机会性病原体，会引起人类和动物的许多感染。抗生素的不当使用促进了甲氧西林耐药金黄色葡萄球菌（MRSA）的传播，使寻找抗微生物药物的努力化为泡影。噁二唑杂环代表了用于开发新药物的特权骨架，因为它们具有独特的生物同位素性能、易于合成和治疗潜力。已经发现了大量含有噁二唑的衍生物作为有效的抗多药耐药MRSA菌株的抗菌剂。在这里，我们研究了一个新的噁二唑化合物库对抗革兰氏阳性和阴性菌株生长的能力。化合物3（4 µM）和12（2 µM）显示出最强的抗菌活性。选择化合物12进行进一步评估，发现其对HaCaT细胞系的细胞毒性低至25 µM，对细菌具有杀菌作用，并能够提高对MRSA的氧氧西林活性。化合物12与氧氧西林的组合值为0.78 μM，氧氧西林为0.06 μg/mL，具有最高的协同作用。FIC指数值为0.396，证实了化合物12和氧氧西林的协同作用。使用化合物12治疗MRSA降低了包括在mec操纵子中的基因的表达。总之，化合物12抑制了MRSA的生长并恢复了氧氧西林的活性，因此在治疗MRSA感染中是一种有前途的化合物。
• Investigation around the Oxadiazole Core in the Discovery of a New Chemotype of Potent and Selective FXR Antagonists
  作者：Carmen Festa、Claudia Finamore、Silvia Marchianò、Francesco Saverio Di Leva、Adriana Carino、Maria Chiara Monti、Federica del Gaudio、Sara Ceccacci、Vittorio Limongelli、Angela Zampella、Stefano Fiorucci、Simona De Marino

  DOI：10.1021/acsmedchemlett.8b00534

  日期：2019.4.11

  antagonists might be useful in the treatment of cholestasis and related metabolic disorders. In this paper, we report the discovery of a new chemotype of FXR antagonists featured by a 3,5-disubstituted oxadiazole core. In total, 35 new derivatives were designed and synthesized, and notably, compounds 3f and 13, containing a piperidine ring, displayed the best antagonistic activity against FXR with

  最近的发现表明，法尼醇X受体（FXR）拮抗剂可能在胆汁淤积症和相关代谢紊乱的治疗中有用。在本文中，我们报告了以3,5-二取代的恶二唑核心为特征的新型FXR拮抗剂化学型的发现。总共设计并合成了35种新的衍生物，尤其是含有哌啶环的化合物3f和13对FXR表现出最佳的拮抗活性，并具有有希望的细胞效价（IC 50分别为0.58±0.27和0.127±0.02μM） 。优异的药代动力学特性使化合物3f成为本研究中鉴定出的最有希望的先导。