3-chloro-N-(5-sulfamoyl-1,3,4-thiadiazol-2-yl)propanamide

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 3-chloro-N-(5-sulfamoyl-1,3,4-thiadiazol-2-yl)propanamide
• 英文别名: 2-(3-Chloropropionylamino)-1,3,4-thiadiazole-5-sulfonamide
• 化学式: C₅H₇ClN₄O₃S₂
• 分子量: 270.721
• InChiKey: XLWGIGRCWQCUAC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.3
• 重原子数：
  15
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  152
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  吗啉 、 3-chloro-N-(5-sulfamoyl-1,3,4-thiadiazol-2-yl)propanamide 在 三乙胺 作用下， 以 四氢呋喃 为溶剂， 反应 20.0h， 以82%的产率得到3-morpholino-N-(5-sulfamoyl-1,3,4-thiadiazol-2-yl)propanamide
  参考文献：
  名称：

  Optimization of Acetazolamide-Based Scaffold as Potent Inhibitors of Vancomycin-Resistant Enterococcus

  摘要：

  Vancomycin-resistant enterococci (VRE) are the second leading cause of hospital-acquired infections (HAIs) attributed to a drug-resistant bacterium in the United States, and resistance to the frontline treatments is well documented. To combat VRE, we have repurposed the FDA-approved carbonic anhydrase drug acetazolamide to design potent antienterococcal agents. Through structure-activity relationship optimization we have arrived at two leads possessing improved potency against clinical VRE strains from MIC = 2 mu g/mL (acetazolamide) to MIC = 0.007 mu g/mL (22) and 1 mu g/mL (26). Physicochemical properties were modified to design leads that have either high oral bioavailability to treat systemic infections or low intestinal permeability to treat VRE infections in the gastrointestinal tract. Our data suggest the intracellular targets for the molecules are putative alpha-carbonic and gamma-carbonic anhydrases, and homology modeling and molecular dynamics simulations were performed. Together, this study presents potential anti-VRE therapeutic options to provide alternatives for problematic VRE infections.

  DOI：

  10.1021/acs.jmedchem.0c00734
• 作为产物：
  描述：

  5-氨基-1,3,4-噻二唑-2-磺酰胺 、 3-氯丙酰氯 在 N-乙基吗啉 作用下， 以 四氢呋喃 为溶剂， 以62%的产率得到3-chloro-N-(5-sulfamoyl-1,3,4-thiadiazol-2-yl)propanamide
  参考文献：
  名称：

  碳酸酐酶抑制剂。通过尾巴方法获得的新型磺胺/乙酰唑酰胺衍生物及其与胞质同工酶I和II，以及与肿瘤相关的同工酶IX的相互作用。

  摘要：

  通过使磺酰胺或5-氨基-1,3,4-噻二唑-2-磺酰胺与ω-氯链烷酰氯反应，然后用仲胺代替ω-氯原子，获得了一系列磺酰胺。已通过含有两个至五个碳原子的烷酰基-羧酰胺基连接体将掺有属于吗啉，哌啶和哌嗪环系统的杂环胺的尾巴连接至这些磺酰胺。测试了以此方式制备的新衍生物作为三种碳酸酐酶（CA，EC 4.2.1.1）同工酶，胞质同工酶CA I和II以及跨膜，肿瘤相关同工酶CA IX的催化域的抑制剂。在芳族和杂环磺酰胺系列中都检测到了几种低纳摩尔CA I和CA II抑制剂，

  DOI：

  10.1016/j.bmcl.2004.10.070

文献信息

• Carbonic anhydrase inhibitors. Novel sulfanilamide/acetazolamide derivatives obtained by the tail approach and their interaction with the cytosolic isozymes I and II, and the tumor-associated isozyme IX
  作者：Hasan Turkmen、Mustafa Durgun、Serpil Yilmaztekin、Mahmut Emul、Alessio Innocenti、Daniela Vullo、Andrea Scozzafava、Claudiu T. Supuran

  DOI：10.1016/j.bmcl.2004.10.070

  日期：2005.1

  containing from two to five carbon atoms. The new derivatives prepared in this way were tested as inhibitors of three carbonic anhydrase (CA, EC 4.2.1.1) isozymes, the cytosolic isozymes CA I and II, and the catalytic domain of the transmembrane, tumor-associated isozyme CA IX. Several low nanomolar CA I and CA II inhibitors were detected both in the aromatic and heterocyclic sulfonamide series, whereas

  通过使磺酰胺或5-氨基-1,3,4-噻二唑-2-磺酰胺与ω-氯链烷酰氯反应，然后用仲胺代替ω-氯原子，获得了一系列磺酰胺。已通过含有两个至五个碳原子的烷酰基-羧酰胺基连接体将掺有属于吗啉，哌啶和哌嗪环系统的杂环胺的尾巴连接至这些磺酰胺。测试了以此方式制备的新衍生物作为三种碳酸酐酶（CA，EC 4.2.1.1）同工酶，胞质同工酶CA I和II以及跨膜，肿瘤相关同工酶CA IX的催化域的抑制剂。在芳族和杂环磺酰胺系列中都检测到了几种低纳摩尔CA I和CA II抑制剂，
• Synthesis and investigation of inhibition effects of new carbonic anhydrase inhibitors
  作者：Oktay Arslan、Ö. Irfan Küfrevioğlu、Barbaros Nalbantoğlu

  DOI：10.1016/s0968-0896(96)00272-6

  日期：1997.3

  Three new derivatives of 2-substituted 1,3,4-thiadiazole-5-sulfonamide have been synthesized. These compounds are 2-(3-chloropropionylamino)-1,3,4-thiadiazole-5-sulfonamide (1); 2-(2,2-dichloroacetylamino)-1,3,4-thiadiazole-5-sulfonamide (2); and 2-(3-phenylpropionylamino)-1,3,4-thiadiazole-5-sulfonamide (3). Inhibition effects of these compounds on carbonic anhydrase I and II have been investigated. By comparing I-50 and K-i values of the compounds, it has been found that compound 1 is a more potent inhibitor than acetazolamide (b) on carbonic anhydrase II. (C) 1997 Elsevier Science Ltd.
• Optimization of Acetazolamide-Based Scaffold as Potent Inhibitors of Vancomycin-Resistant <i>Enterococcus</i>
  作者：Jatinder Kaur、Xufeng Cao、Nader S. Abutaleb、Ahmed Elkashif、Amanda L. Graboski、Aaron D. Krabill、Ahmed Hassan AbdelKhalek、Weiwei An、Atul Bhardwaj、Mohamed N. Seleem、Daniel P. Flaherty

  DOI：10.1021/acs.jmedchem.0c00734

  日期：2020.9.10

  Vancomycin-resistant enterococci (VRE) are the second leading cause of hospital-acquired infections (HAIs) attributed to a drug-resistant bacterium in the United States, and resistance to the frontline treatments is well documented. To combat VRE, we have repurposed the FDA-approved carbonic anhydrase drug acetazolamide to design potent antienterococcal agents. Through structure-activity relationship optimization we have arrived at two leads possessing improved potency against clinical VRE strains from MIC = 2 mu g/mL (acetazolamide) to MIC = 0.007 mu g/mL (22) and 1 mu g/mL (26). Physicochemical properties were modified to design leads that have either high oral bioavailability to treat systemic infections or low intestinal permeability to treat VRE infections in the gastrointestinal tract. Our data suggest the intracellular targets for the molecules are putative alpha-carbonic and gamma-carbonic anhydrases, and homology modeling and molecular dynamics simulations were performed. Together, this study presents potential anti-VRE therapeutic options to provide alternatives for problematic VRE infections.