N-(5-sulfamoyl-1,3,4-thiadiazol-2-yl)pivalamide | 170969-18-3

• 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-sulfamoyl-1,3,4-thiadiazol-2-yl)pivalamide
• 英文别名: 2,2-dimethyl-N-(5-sulfamoyl-1,3,4-thiadiazol-2-yl)propanamide
• CAS: 170969-18-3
• 化学式: C₇H₁₂N₄O₃S₂
• 分子量: 264.329
• InChiKey: FNKGYWFCFILCJW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  16
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.57
• 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 、 三甲基乙酰氯 在 吡啶 作用下， 以 乙腈 为溶剂， 以82.1%的产率得到N-(5-sulfamoyl-1,3,4-thiadiazol-2-yl)pivalamide
  参考文献：
  名称：

  肿瘤相关碳酸酐酶IX的纳摩尔抑制作用的结构基础：乙酰唑胺骨架的亲脂性抑制剂的X射线晶体学和抑制研究

  摘要：

  这项研究提供了一系列具有乙酰唑酰胺骨架的亲脂性碳酸酐酶（CA）抑制剂的结构-活性关系研究。测试了抑制剂对肿瘤表达的CA同工酶IX（CA IX），胞质CA I，CA II和膜结合CA IV的作用。该研究确定了几种针对CA IX的低纳摩尔强效抑制剂，亲脂性跨越两个对数单位。非常有效的泛抑制剂与抗CA IX纳摩尔效力和亚纳摩尔效力针对CA II和IV CA，并用抗大小的CA我一个顺序比母体乙酰唑胺更好效力1在这项研究中，还鉴定出了与对膜结合的CA IV具有选择性的化合物。全面的X射线晶体学研究（12个晶体结构）涉及CA II和可溶CA IX模拟物（CA IX-mimic），揭示了这种特殊抑制曲线的结构基础，并为进一步开发更有效和更广泛的应用奠定了基础。肿瘤表达的CA IX的选择性抑制剂。

  DOI：

  10.1021/acs.jmedchem.0c01390

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。
• 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.
• Almajan, Laura G.; Supuran, Claudiu T., Revue Roumaine de Chimie, 1997, vol. 42, # 7, p. 593 - 597
  作者：Almajan, Laura G.、Supuran, Claudiu T.

  DOI：——

  日期：——
• 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.
• Structural Basis of Nanomolar Inhibition of Tumor-Associated Carbonic Anhydrase IX: X-Ray Crystallographic and Inhibition Study of Lipophilic Inhibitors with Acetazolamide Backbone
  作者：Jacob T. Andring、Mallorie Fouch、Suleyman Akocak、Andrea Angeli、Claudiu T. Supuran、Marc A. Ilies、Robert McKenna

  DOI：10.1021/acs.jmedchem.0c01390

  日期：2020.11.12

  This study provides a structure–activity relationship study of a series of lipophilic carbonic anhydrase (CA) inhibitors with an acetazolamide backbone. The inhibitors were tested against the tumor-expressed CA isozyme IX (CA IX), and the cytosolic CA I, CA II, and membrane-bound CA IV. The study identified several low nanomolar potent inhibitors against CA IX, with lipophilicities spanning two log

  这项研究提供了一系列具有乙酰唑酰胺骨架的亲脂性碳酸酐酶（CA）抑制剂的结构-活性关系研究。测试了抑制剂对肿瘤表达的CA同工酶IX（CA IX），胞质CA I，CA II和膜结合CA IV的作用。该研究确定了几种针对CA IX的低纳摩尔强效抑制剂，亲脂性跨越两个对数单位。非常有效的泛抑制剂与抗CA IX纳摩尔效力和亚纳摩尔效力针对CA II和IV CA，并用抗大小的CA我一个顺序比母体乙酰唑胺更好效力1在这项研究中，还鉴定出了与对膜结合的CA IV具有选择性的化合物。全面的X射线晶体学研究（12个晶体结构）涉及CA II和可溶CA IX模拟物（CA IX-mimic），揭示了这种特殊抑制曲线的结构基础，并为进一步开发更有效和更广泛的应用奠定了基础。肿瘤表达的CA IX的选择性抑制剂。