3,3-dimethyl-N-(5-sulfamoyl-1,3,4-thiadiazol-2-yl)butanamide

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 3,3-dimethyl-N-(5-sulfamoyl-1,3,4-thiadiazol-2-yl)butanamide
• 化学式: C₈H₁₄N₄O₃S₂
• 分子量: 278.356
• InChiKey: AIUQGMPTKDQLOB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  17
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  152
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  5-氨基-1,3,4-噻二唑-2-磺酰胺 、 3,3-二甲基丁酰氯 在 三乙胺 作用下， 以 乙腈 为溶剂， 反应 14.0h， 以43%的产率得到3,3-dimethyl-N-(5-sulfamoyl-1,3,4-thiadiazol-2-yl)butanamide
  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

文献信息

• [EN] CARBONIC ANHYDRASE INHIBITORS AND ANTIBIOTICS AGAINST MULTIDRUG RESISTANT BACTERIA<br/>[FR] INHIBITEURS D'ANHYDRASE CARBONIQUE ET ANTIBIOTIQUES CONTRE DES BACTÉRIES MULTIRÉSISTANTES
  申请人：PURDUE RESEARCH FOUNDATION

  公开号：WO2020131980A1

  公开（公告）日：2020-06-25

  The invention described herein generally relates to novel therapeutic compounds, and in particular to carbonic anhydrase inhibitors as a narrow spectrum antibiotics against drug resistant bacteria and methods for treating those infection diseases in mammals using the described carbonic anhydrase inhibitors or a pharmaceutical formulation thereof.

  本发明通常涉及新型治疗化合物，特别是作为一种针对耐药细菌的窄谱抗生素的碳酸酐酶抑制剂，以及使用所述碳酸酐酶抑制剂或其制药配方治疗哺乳动物感染疾病的方法。
• CARBONIC ANHYDRASE INHIBITORS FOR TREATMENT OF NEISSERIA GONORRHOEAE INFECTION
  申请人：Purdue Research Foundation

  公开号：US20220213047A1

  公开（公告）日：2022-07-07

  The invention described generally relates to novel therapeutic compounds, and in particular to carbonic anhydrase inhibitors as an antibiotic against Neisseria gonorrhea bacteria and methods for treating those sexually transmitted infection diseases in mammals using the described carbonic anhydrase inhibitors having a formula (I), or a pharmaceutical formulation thereof, alone or together with one or more other antibiotics.
• 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.