N-(5-nitrothiazol-2-yl)furan-3-carboxamide | 1236429-42-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: N-(5-nitrothiazol-2-yl)furan-3-carboxamide
• 英文别名: N-(5-nitro-1,3-thiazol-2-yl)furan-3-carboxamide
• CAS: 1236429-42-7
• 化学式: C₈H₅N₃O₄S
• mdl: MFCD23134354
• 分子量: 239.211
• InChiKey: KGPMZTJTZUAJHH-UHFFFAOYSA-N

物化性质

• 密度：
  1.642±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  129
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  3-呋喃甲酰氯 、 2-氨基-5-硝基噻唑 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 24.0h， 以53%的产率得到N-(5-nitrothiazol-2-yl)furan-3-carboxamide
  参考文献：
  名称：

  杂芳基硝唑尼特类似物的合成、体外生物测定和计算研究

  摘要：

  抗原虫药物硝唑尼特（NTZ）已显示出多种药理学特性，并已出现在多项临床试验中。在此，我们介绍了 NTZ 的四种杂芳基酰胺类似物的合成、表征、体外生物学研究和计算机研究。在合成的分子中，化合物2和化合物4对大肠杆菌( E.coli )表现出良好的抗菌活性，体外抗菌试验显示其优于母药硝唑尼特。化合物2显示出 20 mm 的抑制区，是最低浓度 (12.5 µg/ml) 母药 NTZ (10 mm) 的两倍。化合物1也表现出与硝唑尼特相似的抗菌作用。还通过在HeLa细胞系中采用细胞计数试剂盒 8 (CCK-8) 测定技术测试了类似物的体外细胞毒活性，化合物2被鉴定为潜在的抗癌剂，其 IC 50值为 172 µg，这证明了其比硝唑尼特更有效 (IC 50 = 428 µg)。此外，这些化合物还针对各种细菌和癌症信号蛋白进行了分子对接研究。体外测试结果证实了计算机对接研究，化合物2和化合物4对蛋白质具

  DOI：

  10.1002/prp2.800

文献信息

• Synthesis and Antimicrobial Evaluation of Nitazoxanide-Based Analogues: Identification of Selective and Broad Spectrum Activity
  作者：T. Eric Ballard、Xia Wang、Igor Olekhnovich、Taylor Koerner、Craig Seymour、Joseph Salamoun、Michelle Warthan、Paul S. Hoffman、Timothy L. Macdonald

  DOI：10.1002/cmdc.201000475

  日期：2011.2.7

  library composed of nitazoxanide‐based analogues was synthesized and assayed for increased antibacterial efficacy against the pyruvate–ferredoxin oxidoreductase (PFOR) using microorganisms Helicobacter pylori, Campylobacter jejuni and Clostridium difficile. Derivatives were found to recapitulate and improve activity against these organisms and select analogues were tested for their ability to disrupt

  合成了一个由基于硝唑尼特的类似物组成的文库，并使用微生物幽门螺杆菌、空肠弯曲杆菌和艰难梭菌对丙酮酸-铁氧还蛋白氧化还原酶 (PFOR) 的抗菌功效进行了分析。发现衍生物可以概括并提高针对这些生物的活性，并测试了选择的类似物直接破坏 PFOR 酶的能力。该文库还针对葡萄球菌的活性进行了筛选，并鉴定出能够以低微摩尔最低抑制浓度抑制葡萄球菌和所有 PFOR 生物体的类似物，并且对人类包皮细胞的毒性较低。
• BROAD SPECTRUM BENZOTHIOPHENE-NITROTHIAZOLIDE AND OTHER ANTIMICROBIALS
  申请人：Hoffman Paul S.

  公开号：US20120010187A1

  公开（公告）日：2012-01-12

  The invention provides FIG. 1 novel antimicrobial chemical entities based on a nitrothiazolide backbone that exhibit antibacterial and antiparasitic action against a wide range of human pathogens. The new classes of compounds show extended action against Gram positive bacteria including MRSA drug resistant pathogens. In the Gram-positive organisms, they specifically target and functionally inhibit microbial attachment to surfaces and biofilm formation. In Gram-negative bacteria, including enteroaggregative E. coli strains, these compounds function as pilicides by inhibiting the assembly of pilin subunits into adhesive filaments. Several of these compounds show potent antimicrobial action against Gram positive bacteria, perhaps involving novel targets. Many of the benzothiophene derivatives exhibit antimicrobial activity in the low micrograms per ml range and in blocking biofilm formation in the nanomolar range; ranges considered are well within the range of utility as therapeutics.

  本发明提供了基于硝基噻唑骨架的新型抗微生物化合物，能够对广泛的人类病原体表现出抗菌和抗寄生虫作用。这些新型化合物能够延长对革兰氏阳性菌的作用，包括对耐药菌MRSA的作用。在革兰氏阳性生物中，它们能够特异性地靶向和功能性地抑制微生物对表面的附着和生物膜形成。在革兰氏阴性细菌中，包括肠毒性E. coli菌株，这些化合物通过抑制毛细管亚单位的组装成为粘附纤维，发挥作为毛细管抑制剂的作用。其中几种化合物对革兰氏阳性菌表现出强效的抗微生物活性，可能涉及新的靶点。许多苯并噻吩衍生物在低微克/毫升范围内表现出抗微生物活性，并在纳摩尔范围内阻止生物膜形成；这些范围被认为是治疗上实用的范围。
• COMPOSITIONS AND METHODS FOR TREATING TUBERCULOSIS
  申请人：Hoffman Paul S.

  公开号：US20130317070A1

  公开（公告）日：2013-11-28

  The invention provides for the use of antimicrobial chemical entities based on a nitrothiazolide backbone that exhibit anti-mycobacteria activity, including the mycobacterium causing tuberculosis. Multiple compounds were synthesized and screened for anti-tuberculosis activity. Disclosed herein are a series of compounds with anti-tuberculosis activity, including six leads that completely inhibited bacterial growth at 5 micrograms per ml or less. Three of these compounds were tested to determine MIC and these ranged between 1 and 4 micrograms per ml against both drug susceptible Mycobacterium tuberculosis strains and strains that are multi-drug resistant (MDR) including XDR strains. The compounds developed are derived from parent compound nitazoxanide, which had no inhibitory activity in the stringent testing format used herein. The derivatives were synthesized using a di-nitro-thiophene or 4-Chloro-5-Nitro-thiazole scaffold and R groups connected via a peptide bond (NHCO) to cyclic compounds such as benzene, thiophene or furans. Many of these compounds have broad spectrum activity against Gram positive bacteria including Staphylococcus aureus (MRSA) and Staphylococcus epidermidis . Several of these lead compounds were not toxic for mice at 200 mg/Kg doses administered over a period of three days.

  本发明提供了基于硝基噻唑骨架的抗微生物化学实体的使用，其表现出抗分枝杆菌活性，包括导致结核病的分枝杆菌。多种化合物被合成并筛选以寻找抗结核病活性。本文披露了一系列具有抗结核病活性的化合物，包括六个引物，其在5微克/毫升或更低浓度下完全抑制了细菌生长。其中三种化合物被测试以确定MIC，这些化合物对药物敏感的结核分枝杆菌菌株和多重耐药（MDR）菌株（包括XDR菌株）的MIC范围在1至4微克/毫升之间。开发的化合物来源于父化合物硝唑酮，该化合物在本文所使用的严格测试格式中没有抑制活性。这些衍生物是使用二硝基噻吩或4-氯-5-硝基噻唑支架和连接到环化合物（如苯、噻吩或呋喃）的R基通过肽键（NHCO）合成的。其中许多化合物对革兰氏阳性细菌具有广谱活性，包括金黄色葡萄球菌（MRSA）和表皮葡萄球菌。其中几种引物化合物在3天内以200毫克/千克的剂量给小鼠注射时没有毒性。
• Biological activity of modified and exchanged 2-amino-5-nitrothiazole amide analogues of nitazoxanide
  作者：T. Eric Ballard、Xia Wang、Igor Olekhnovich、Taylor Koerner、Craig Seymour、Paul S. Hoffman、Timothy L. Macdonald

  DOI：10.1016/j.bmcl.2010.04.126

  日期：2010.6

  Head group analogues of the antibacterial and antiparasitic drug nitazoxanide (NTZ) are presented. A library of 39 analogues was synthesized and assayed for their ability to suppress growth of Helicobacter pylori, Campylobacter jejuni, Clostridium difficile and inhibit NTZ target pyruvate: ferredoxin oxidoreductase (PFOR). Two head groups assayed recapitulated NTZ activity and possessed improved activity over their 2-amino-5-nitrothiazole counterparts, demonstrating that head group modification is a viable route for the synthesis of NTZ-related antibacterial analogues. (C) 2010 Elsevier Ltd. All rights reserved.
• THIOPHENE DERIVATIVES FOR USE IN THE TREATMENT OF TUBERCULOSIS
  申请人：University of Virginia Patent Foundation

  公开号：EP2632460B1

  公开（公告）日：2018-02-28