2-azido-N-(2,4-dimethylphenyl)acetamide | 847149-83-1

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: 2-azido-N-(2,4-dimethylphenyl)acetamide
• CAS: 847149-83-1
• 化学式: C₁₀H₁₂N₄O
• 分子量: 204.231
• InChiKey: XHMBUYCPDGMHHG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  15
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  43.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-azido-N-(2,4-dimethylphenyl)acetamide 、 2-氰基-N-(3,4-二甲基苯基)-乙酰胺 在 caesium carbonate 作用下， 以 水 、 二甲基亚砜 为溶剂， 反应 24.0h， 以31%的产率得到5-amino-1-[2-(2,4-dimethylanilino)-2-oxoethyl]-N-(3,4-dimethylphenyl)triazole-4-carboxamide
  参考文献：
  名称：

  Advancement of the 5-Amino-1-(Carbamoylmethyl)-1H-1,2,3-Triazole-4-Carboxamide Scaffold to Disarm the Bacterial SOS Response

  摘要：

  Many antibiotics, either directly or indirectly, cause DNA damage thereby activating the bacterial DNA damage (SOS) response. SOS activation results in expression of genes involved in DNA repair and mutagenesis, and the regulation of the SOS response relies on two key proteins, LexA and RecA. Genetic studies have indicated that inactivating the regulatory proteins of this response sensitizes bacteria to antibiotics and slows the appearance of resistance. However, advancement of small molecule inhibitors of the SOS response has lagged, despite their clear promise in addressing the threat of antibiotic resistance. Previously, we had addressed this deficit by performing a high throughput screen of similar to 1.8 million compounds that monitored for inhibition of RecA-mediated auto-proteolysis of Escherichia coli LexA, the reaction that initiates the SOS response. In this report, the refinement of the 5-amino-1-(carbamoylmethyl)-1H-1,2,3-triazole-4-carboxamide scaffold identified in the screen is detailed. After development of a modular synthesis, a survey of key activity determinants led to the identification of an analog with improved potency and increased breadth, targeting auto-proteolysis of LexA from both E. coli and Pseudomonas aeruginosa. Comparison of the structure of this compound to those of others in the series suggests structural features that may be required for activity and cross-species breadth. In addition, the feasibility of small molecule modulation of the SOS response was demonstrated in vivo by the suppression of the appearance of resistance. These structure activity relationships thus represent an important step toward producing Drugs that Inhibit SOS Activation to Repress Mechanisms Enabling Resistance (DISARMERs).

  DOI：

  10.3389/fmicb.2018.02961
• 作为产物：
  描述：

  2-氯-n-(2,4-二甲基苯基)乙酰胺 在 sodium azide 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 2-azido-N-(2,4-dimethylphenyl)acetamide
  参考文献：
  名称：

  新型三嗪-三唑衍生物作为潜在的α-葡萄糖苷酶抑制剂的合成，体外评价和分子对接研究

  摘要：

  合成了一系列新颖的三嗪-三唑衍生物7a – 7m，通过1 H NMR表征并评估了其对α-葡萄糖苷酶的抑制活性。与标准药物阿卡波糖相比（IC 50  = 817.38±6.27μM），所有合成的化合物均显示出有效的α-葡萄糖苷酶抑制活性，IC 50范围为11.63±0.15至37.44± 0.35μM。在该系列中，化合物7i（IC 50 = 11.63±0.15μM），在苯环上带有2,5-二氯取代基，表示最有效的α-葡萄糖苷酶抑制活性。还用同源性建模的α-葡萄糖苷酶对活性最高的化合物进行了分子对接研究，以探索可能的抑制机制。我们的研究表明，这些三嗪-三唑衍生物是一类新的α-葡萄糖苷酶抑制剂。

  DOI：

  10.1016/j.ejmech.2016.09.067

文献信息

• Synthesis and biological evaluation of novel 2,4,5-triarylimidazole–1,2,3-triazole derivatives via click chemistry as α-glucosidase inhibitors
  作者：Guangcheng Wang、Zhiyun Peng、Jing Wang、Juan Li、Xin Li

  DOI：10.1016/j.bmcl.2016.10.057

  日期：2016.12

  A novel series of 2,4,5-triarylimidazole-1,2,3-triazole derivatives were synthesized via copper(I)-catalyzed azide-alkyne click chemistry, and evaluated for their α-glucosidase inhibitory activity. All tested compounds showed potent α-glucosidase inhibitory activity with IC50 ranging from 15.16±0.18 to 48.15±0.37μM, in comparison to the standard drug, acarbose (IC50=817.38±6.27μM). Among all the tested

  通过铜（I）催化的叠氮化物-炔炔点击化学合成了一系列新的2,4,5-三芳基咪唑-1,2,3-三唑衍生物，并对其α-葡萄糖苷酶抑制活性进行了评估。与标准药物阿卡波糖（IC50 = 817.38±6.27μM）相比，所有测试化合物均显示出有效的α-葡萄糖苷酶抑制活性，IC50为15.16±0.18至48.15±0.37μM。在所有测试的化合物中，发现5j是最具活性的化合物，IC50值为15.16±0.18μM，并且表现为非竞争性抑制剂，Ki为14.78μM。另外，进行了分子对接研究以探索这些化合物与α-葡萄糖苷酶的结合相互作用。
• Design and synthesis of new indanol-1,2,3-triazole derivatives as potent antitubercular and antimicrobial agents
  作者：Pramod S. Phatak、Rajubai D. Bakale、Ravibhushan S. Kulkarni、Sambhaji T. Dhumal、Prashant P. Dixit、Vagolu Siva Krishna、Dharmarajan Sriram、Vijay M. Khedkar、Kishan P. Haval

  DOI：10.1016/j.bmcl.2020.127579

  日期：2020.11

  antitubercular agents, herein we have reported a series of new thirty-two indanol-1,2,3-triazole derivatives. The synthesized compounds were screened for their in vitro antitubercular and antimicrobial activities. Among the screened compounds, most of the compounds have displayed good antitubercular activity against Mycobacterium tuberculosis H37Rv. The compound 5g has been identified as potent antitubercular

  为了寻找新的抗结核药，我们在此报道了一系列新的三十二种茚满醇-1,2,3-三唑衍生物。筛选合成的化合物的体外抗结核和抗菌活性。在筛选的化合物中，大多数化合物对结核分枝杆菌H37Rv表现出良好的抗结核活性。化合物5g已被确定为有效的抗结核药，MIC值为1.56 µM。使用MTT分析进一步研究了该系列中活性最高的化合物对HEK 293细胞的细胞毒性，发现无毒。另外，显示出十种化合物对抗菌和抗真菌病原体均具有良好的抗菌活性。针对的分子对接研究进行了分枝杆菌烯酰-ACP-还原酶（InhA）以深入了解抗结核作用的分子机制。研究了这些化合物的药代动力学参数，并显示了可接受的药物相似度评分。
• Synthesis, biological evaluation, and docking study of a series of 1,4‐disubstituted 1,2,3‐triazole derivatives with an indole‐triazole‐peptide conjugate
  作者：Srinivas Suryapeta、Neeraja Papigani、Venkanna Banothu、Pramod Kumar Dubey、Khagga Mukkanti、Sarbani Pal

  DOI：10.1002/jhet.4020

  日期：2020.8

  synthesized derivatives were screened for their antimicrobial activities against one gram‐positive (Staphylococcus aureus ) and three gram‐negative (Escherichia coli , Klebsiella pneumonia , and Proteus vulgaris ) bacteria using an agar‐well diffusion method. Most of the compounds showed moderate to reasonable antibacterial activities especially the compound 9e that showed good activities against all the

  设计了一系列含有吲哚-三唑-肽共轭物的新化合物，作为具有双重抗菌和抗癌活性的潜在药物。因此，通过多步合成制备了20种化合物，其中包括铜催化的叠氮化物-炔烃环加成（CuAAC），这是中高收率的关键步骤。所有合成的化合物均通过色谱技术纯化，并通过IR，1 H和13 C NMR和质谱数据表征。筛选了合成衍生物对一种革兰氏阳性菌（金黄色葡萄球菌）和三种革兰氏阴性菌（大肠杆菌，克雷伯菌肺炎和普通变形杆菌（Proteus vulgaris）细菌采用琼脂井扩散法。大多数化合物显示出中等至合理的抗菌活性，尤其是化合物9e对所有菌株均表现出良好的活性。通过使用Autodock Vina软件在计算机上进行的分子对接研究，评估了该化合物的DNA促旋酶抑制活性的潜力。化合物9e的低ΔG结合值（-9.4 Kcal / mol）表明其与靶蛋白在计算机上具有良好的相互作用。使用人肺癌细胞系A549通过MTT分析评估了某
• TEAD–YAP Interaction Inhibitors and MDM2 Binders from DNA‐Encoded Indole‐Focused Ugi Peptidomimetics
  作者：Verena B. K. Kunig、Marco Potowski、Mohammad Akbarzadeh、Mateja Klika Škopić、Denise Santos Smith、Lukas Arendt、Ina Dormuth、Hélène Adihou、Blaž Andlovic、Hacer Karatas、Shabnam Shaabani、Tryfon Zarganes‐Tzitzikas、Constantinos G. Neochoritis、Ran Zhang、Matthew Groves、Stéphanie M. Guéret、Christian Ottmann、Jörg Rahnenführer、Roland Fried、Alexander Dömling、Andreas Brunschweiger

  DOI：10.1002/anie.202006280

  日期：2020.11.9

  encoded by DNA sequences, and substituted by azide‐alkyne cycloaddition to yield a library of 8112 molecules. Selection experiments for the tumor‐relevant proteins MDM2 and TEAD4 yielded MDM2 binders and a novel class of TEAD‐YAP interaction inhibitors that perturbed the expression of a gene under the control of these Hippo pathway effectors.

  DNA 编码的组合合成提供了对特权分子结构周围化学空间的有效和密集覆盖。色氨酸的吲哚侧链在蛋白质-蛋白质相互作用的关键或“热点”区域中发挥着重要作用。基于 Ugi 四组分反应设计了一个 DNA 编码的组合拟肽文库，采用色氨酸模拟吲哚侧链探测靶蛋白表面。在化学稳定的六胸苷衔接寡核苷酸“hexT”上合成了几种拟肽，由 DNA 序列编码，并通过叠氮化物-炔烃环加成取代，产生 8112 个分子的文库。
• Aminofurazan compounds useful as protein kinase inhibitors
  申请人：Come H. Jon

  公开号：US20050148640A1

  公开（公告）日：2005-07-07

  The present invention relates to compounds useful of inhibitors of protein kinases. The invention also provides pharmaceutically acceptable compositions comprising said compounds and methods of using the compositions in the treatment of various disease, conditions, or disorders.

  本发明涉及一种有用的蛋白激酶抑制剂化合物。本发明还提供了包括上述化合物的药学上可接受的组合物，并提供了使用这些组合物治疗各种疾病、病况或障碍的方法。