N-(2-苯并噻唑)-乙酰乙酰胺 | 4692-94-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并噻唑类
• 中文名称: N-(2-苯并噻唑)-乙酰乙酰胺
• 英文名称: N-(2-benzothiazolyl)-3-oxobutanamide
• 英文别名: N-(benzo[d]thiazol-2-yl)-3-oxobutanamide；N-(1,3-benzothiazol-2-yl)-3-oxobutanamide；Acetoacetamide, N-(2-benzothiazolyl)-
• CAS: 4692-94-8
• 化学式: C₁₁H₁₀N₂O₂S
• mdl: MFCD00022861
• 分子量: 234.279
• InChiKey: KRVAVIMTIIEASB-UHFFFAOYSA-N

物化性质

• 熔点：
  219 °C
• 密度：
  1.3042 (rough estimate)

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  16
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.181
• 拓扑面积：
  87.3
• 氢给体数：
  1
• 氢受体数：
  4

安全信息

• 海关编码：
  2934200090
• 储存条件：
  应将产品存放在通风、低温、干燥的地方，并与其他库房内的食品原料分开存放。

制备方法与用途

类别：有毒物品

• 毒性分级：高毒
• 急性毒性：静脉-小鼠 LD50 为 56 毫克/公斤
• 可燃性危险特性：可燃；燃烧时产生有毒的氮氧化物和硫化物烟雾
• 储运特性：通风、低温干燥，与库房食品原料分开存放
• 灭火剂：干粉、泡沫、沙土、二氧化碳、雾状水

反应信息

• 作为反应物：
  描述：

  N-(2-苯并噻唑)-乙酰乙酰胺 在 盐酸 、 ammonium acetate 、 sodium nitrite 作用下， 以 水 为溶剂， 反应 0.5h， 生成 N-1,3-benzothiazol-2-yl-1-(4-chlorophenyl)-5-cyano-4-methyl-6-oxo-1,6-dihydropyridazine-3-carboxamide
  参考文献：
  名称：

  杂环合成中的-氧代苯甲酰胺：吡嗪酮，吡唑并哒嗪和辛啉的新型合成

  摘要：

  化合物1与芳族重氮盐平稳偶联，得到相应的芳基hydr2a-d。化合物2a-d与DMF-DMA在回流的二甲苯中缩合，得到吡啶并酮3a-d。基于化合物3a-d与一些活性亚甲基试剂和一些亲核试剂的进一步反应，还建立了化合物3a-d。因此，在回流的乙醇哌啶中3a，b与丙二腈的反应得到芳基丙二腈4a，b。哒嗪酮衍生物3a，b与水合肼反应，得到肼衍生物5a，b。当3a，b与无溶剂的水合肼熔融时，得到吡唑并[4，3-c]-哒嗪6a，b。当化合物5a，b在熔点上短时间熔融时，也获得了化合物6a，b。2a，b与氰基乙酸乙酯缩合得到7a，b。同样，2a的反应 b与1摩尔丙二腈一起提供哒嗪衍生物8a，b。同时，在相同的实验条件下，当2摩尔丙二腈与2a，b反应时，可生成cinnoline衍生物（9a，b）。哒嗪8a，b与1摩尔丙二腈反应，得到9。化合物2b与芳基丙二腈和丙烯腈的混合物反应，得到配制成三唑部分12a

  DOI：

  10.21608/ejchem.2018.3901.1343
• 作为产物：
  描述：

  苯胺 在 溴 、 sodium hydroxide 作用下， 以 甲苯 为溶剂， 反应 18.0h， 生成 N-(2-苯并噻唑)-乙酰乙酰胺
  参考文献：
  名称：

  Development of selective DprE1 inhibitors: Design, synthesis, crystal structure and antitubercular activity of benzothiazolylpyrimidine-5-carboxamides

  摘要：

  Decaprenylphosphoryl-b-D-ribose 20-epimerase (DprE1) is a potential drug target for development of antitubercular agents. Structure based drug discovery approach yielded twenty novel derivatives of benzothiazolylpyrimidine-5-carboxamides (7a-t) which were synthesised by three component one pot reaction involving benzothiazolyl oxobutanamide, thiourea and substituted 'aromatic benzaldehydes. These derivatives were evaluated for antituberculat activity to determine MIC and compound 7a, 7e, 7f and 7o were found to be potentially active against Mycobacterium tuberculosis (H(37)Rv). Log P of these compounds was found to be between 2.0 and 3.0 maldng.them suitable for oral dosing. DprE1 selectivity and pharmacokinetic studies were carried out for these compounds of which 7a and 7o were found to be highly selective and bioavailability was found to be above 52% by oral dose. Crystal structure of 7a was studied and molecular packing was determined, it exhibited a triclinic crystal lattice arrangement having hydrogen bonded dimeric arrangement. Drug receptor interactions were studied which exhibited docking in the active site of receptor with hydrogen bonding, hydrophobic interactions, vdW interactions with amino acid residues such as Cys387, Asn385, Lys418, Tyr314, Gln334 and Lys367 respectively. 3D QSAR analysis was carried out by kNN-MFA method to determine and develop theoretical model, best suitable model was found to be based on Simulated Annealing k-Neariest Neighbour Molecular Field Analysis (SA kNN-MFA). The model provided with hydrophobic descriptors in positive side indicating the need of bulky groups, steric and electronegative descriptors in negative coordinates hints with contribution by the electronegative substitutions as favourable and desirable moieties for enhancing the activity. The q(2), q(2)_se and Pred_r(2)se were found to be 0.5000, 0.6404 and 1.0094 respectively. A pharmacophore model was generated which suggested for necessity of aromatic, aliphatic carbon centre and hydrogen bond donor for development of newer DprE1 selective inhibitors. (C) 2015 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2015.04.011

文献信息

• Reaction of α-oxoketenes with 2-substituted benzothiazoles and benzimidazoles: synthesis of benzo[4,5]thiazolo[3,2-a]pyridinone and N-(1,3-benzothiazol-2-yl)-3-oxopropanamide derivatives
  作者：Mahboobeh Zahedifar、Hassan Sheibani

  DOI：10.1007/s10593-016-1829-3

  日期：2016.1

  cyclocondensation reactions of α-oxoketenes with 2-substituted benzothiazoles have been investigated. Acyl-substituted Meldrum's acids and 1,3-dioxin-4-one derivatives have been used as starting compounds for preparation of α-oxoketenes, which were used in the cycloaddition reactions with (benzothiazol-2-yl)-acetonitrile and (benzimidazol-2-yl)acetonitrile giving good product yields. Also the reaction of (ch

  已经研究了通过α-氧杂环丁烯与2-取代的苯并噻唑的环缩合反应合成嘧啶酮衍生物的快速简便的方法。酰基取代的麦德鲁姆酸和1,3-二恶英-4-酮衍生物已用作制备α-氧杂环丁烯的起始化合物，它们用于与（苯并噻唑-2-基）-乙腈和（苯并咪唑- 2-基）乙腈提供良好的产物收率。还研究了（氯羰基）苯乙烯酮与2-（1,3-苯并噻唑-2-基）乙腈的反应。
• Etude de la fragmentation par impact électronique de dérivés du benzothiazole
  作者：Saturnin Claude、Raffaele Tabacchi、Laurent Due、Rudolf Fuchs、Karl-Josef Boosen

  DOI：10.1002/hlca.19800630318

  日期：1980.4.23

  Study of Electron-Impact Fragmentation of Benzothiazole Derivatives

  苯并噻唑衍生物的电子碰撞裂解研究
• Antiproliferative effect, alteration of cancer cell cycle progression and potential MET kinase inhibition induced by 3,4-dihydropyrimidin-2(1H)-one C5 amide derivatives
  作者：Fatemeh Moosavi、Ahmad Ebadi、Maryam Mohabbati、Tahereh Damghani、Motahareh Mortazavi、Ramin Miri、Omidreza Firuzi

  DOI：10.1016/j.ejphar.2021.173850

  日期：2021.3

  4-dihydropyrimidin-2(1H)-one C5 amide derivatives were synthesized and their cancer cell growth inhibitory activity was examined against MCF-7, HT-29 and MOLT-4 cells and also NIH/3T3 non-cancer cells by MTT assay. The antiproliferative effect of the most potent derivatives were tested against MET-dependent EBC-1 and MKN-45, lung and gastric cancer cell lines, respectively. MET kinase inhibition was measured by a

  癌症仍然是全球第二大死亡原因。发现新型治疗剂对于改善我们的医疗管理能力至关重要。MET受体酪氨酸激酶途径的失调在癌症进展中起重要作用，使该受体成为抗癌药物发现的有吸引力的分子靶标。在这项研究中，27，3,4-dihydropyrimidin-2（1 H）合成一种C5酰胺衍生物，并通过MTT分析检测其对MCF-7，HT-29和MOLT-4细胞以及NIH / 3T3非癌细胞的癌细胞生长抑制活性。测试了最有效衍生物的抗增殖作用，分别针对MET依赖的EBC-1和MKN-45，肺癌和胃癌细胞系。通过均相时间分辨荧光（HTRF）测定法测量MET激酶抑制。通过RNase / PI流式细胞术检测受试化合物对细胞周期的影响。许多化合物对乳腺癌和结肠癌以及白血病细胞系表现出相当大的抗增殖作用，相对而言保留非癌细胞。一些衍生物轴承苯并噻唑基甲酰胺部分在C5位（15，21，23，31，和37）显示出最高的活性与IC
• 3,4-Dihydropyrimidin-2(1H)-one C5 Amides as Inhibitors of T NFα Production: Synthesis, Biological Evaluation and Molecular Modeling
  作者：Ahmad Ebadi、Mehdi Khoshneviszadeh、Katayoun Javidnia、Mohammad Hossein Ghahremani、Omidreza Firuzi、Ramin Miri

  DOI：10.2174/1570180814666170306120235

  日期：2017.7.20

  arthritis. Objective: In the present contribution, 16 derivatives of 3,4-dihydropyrimidin-2(1H)-one(thione) C5 amide were synthesized and their anti-inflammatory activities were investigated. Methods: We synthesized 3,4-dihydropyrimidin-2(1H)-one(thione) C5 amide derivatives according to Biginelli method. Inhibitory effect of newly synthesized derivatives was evaluated on TNF-α production in lipopolysaccharide-stimulated

  背景：调节促炎细胞因子尤其是 TNFα 可以在炎症性疾病中发挥治疗作用，这种方法在类风湿性关节炎等疾病的药物开发中备受关注。目的：在目前的贡献中，合成了 16 种 3,4-二氢嘧啶-2(1H)-酮 (硫酮) C5 酰胺的衍生物并研究了它们的抗炎活性。方法：我们根据 Biginelli 方法合成了 3,4-二氢嘧啶-2（1H）-酮（硫酮）C5 酰胺衍生物。评估了新合成衍生物对脂多糖刺激的外周血单核细胞 (PBMC) 中 TNF-α 产生的抑制作用。结果：这些化合物中的大多数都表现出对脂多糖刺激的外周血单核细胞 (PBMC) 中 TNF-α 的良好抑制。化合物 6k 和 6c 显示出最高水平的 TNFα 抑制（在 50 μM 时分别为 74.9 和 72.2）。分子模型研究表明，化合物 6k 与 p38α MAPK 的活性位点形成稳定的复合物。结论：两种最有效化合物的共同结构特征是在 DHPM
• Virtual screening of some heterocyclic structures toward novel antibacterial agents
  作者：Zahra S. Hosseini、Mohammad Reza Housaindokht、Nima Razzaghi-Asl、Ramin Miri

  DOI：10.1007/s13738-017-1262-2

  日期：2018.3

  the most important issues in global health and economy. Moreover, increasing prevalence of antibiotic-resistant pathogenic bacteria necessitates the considerable need for discovering new drugs. Some heterocyclic structures with dihydropyridine (DHP) scaffold have been reported as antimicrobial agents. Herein, we report a structure-based virtual screening of a pool of 3,5-disubstituted DHPs and a post-analysis

  传染病及其治疗是全球健康和经济中最重要的问题。而且，抗生素抗性病原细菌的流行增加使得发现新药的需求很大。已经报道了一些具有二氢吡啶（DHP）支架的杂环结构作为抗菌剂。在这里，我们报告了一个基于结构的3,5-二取代DHP池的虚拟筛选，并通过体外抗菌评估对虚拟命中值进行了后期分析。四个排名最高的DHP结构（6a – d）被发现与相关的靶活性位点相互作用并且在其酶抑制范围内表现出优异的立体电子特征。合成选定的化合物，并通过微稀释法评估其抗菌活性。这项研究的结果代表了多步虚拟筛选策略在确定特权DHP结构方面的重大应用，这些结构是进一步开发更有效的抗菌剂的良好起点。

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