4-氟-N-(5-硝基-1,3-噻唑-2-基)苯甲酰胺 | 326-05-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 4-氟-N-(5-硝基-1,3-噻唑-2-基)苯甲酰胺
• 英文名称: 4-fluoro-N-(5-nitrothiazol-2-yl)benzamide
• 英文别名: 2-(4-fluorobenzamido)-5-nitrothiazole；4-fluoro-N-(5-nitro-thiazol-2-yl)-benzamide；4-Fluor-benzoesaeure-(5-nitro-thiazol-2-ylamid)；4-fluoro-N-(5-nitro-1,3-thiazol-2-yl)benzamide
• CAS: 326-05-6
• 化学式: C₁₀H₆FN₃O₃S
• mdl: MFCD01214158
• 分子量: 267.24
• InChiKey: VZPQIICQNRTBPR-UHFFFAOYSA-N

物化性质

• 密度：
  1.599±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  116
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  对氟苯甲酸 在 氯化亚砜 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 8.0h， 生成 4-氟-N-(5-硝基-1,3-噻唑-2-基)苯甲酰胺
  参考文献：
  名称：

  铜绿假单胞菌Ⅲ型分泌系统抑制剂含噻唑芳酰胺衍生物的设计与合成

  摘要：

  为了鉴定食源性病原体铜绿假单胞菌中 III 型分泌系统 (T3SS) 的有效抑制剂，我们通过主动剪接将水杨酸与各种杂环合并，合成了 35 种含噻唑的芳基酰胺。通过筛选exoS启动子活性，我们从这 35 种化合物中发现了一种高效的 T3SS 抑制剂。通过后续实验，证实化合物II-22特异性靶向铜绿假单胞菌的T3SS。此外，化合物II-22通过调节 CyaB-cAMP/Vfr-ExsA 和 ExsCED-ExsA 调节途径抑制效应蛋白 ExoS 的分泌。此外，化合物II-22抑制了针复合体组装相关基因的转录，从而降低了细菌毒力。通过使用大蜡螟幼虫的接种试验进一步验证了化合物II-22的强大体内功效。研究还表明，化合物II-22增强了 CIP（环丙沙星）和 TOB（妥布霉素）等抗生素的杀菌活性。这些结果可能有助于开发新型抗菌药物以降低细菌耐药性。

  DOI：

  10.1021/acs.jafc.4c02277

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。
• Cavier; Gayral; Guillaumel, European Journal of Medicinal Chemistry, 1978, vol. 13, # 6, p. 539 - 543
  作者：Cavier、Gayral、Guillaumel、et al.

  DOI：——

  日期：——
• 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