丙帕唑胺 | 98-75-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 中文名称: 丙帕唑胺
• 英文名称: N-(5-sulfamoyl-1,3,4-thiadiazol-2-yl)propionamide
• 英文别名: Propazolamide；N-(5-sulfamoyl-1,3,4-thiadiazol-2-yl)propanamide
• CAS: 98-75-9
• 化学式: C₅H₈N₄O₃S₂
• 分子量: 236.276
• InChiKey: PCBBBQKRWNGNDW-UHFFFAOYSA-N

物化性质

• 熔点：
  247-248 °C (decomp)
• 密度：
  1.641±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.2
• 重原子数：
  14
• 可旋转键数：
  3
• 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

安全信息

• 海关编码：
  2935009090

反应信息

• 作为反应物：
  描述：

  哌啶 、 聚合甲醛 、 丙帕唑胺 以 甲醇 、 水 为溶剂， 生成 5-propionylamino-[1,3,4]thiadiazole-2-sulfonic acid piperidin-1-ylmethyl-amide
  参考文献：
  名称：

  曼尼希药用衍生物。2.一些碳酸酐酶抑制剂的衍生物。

  摘要：

  DOI：

  10.1021/jm00287a027
• 作为产物：
  描述：

  5-氨基-1,3,4-噻二唑-2-磺酰胺 、 丙酸酐 以 乙腈 为溶剂， 以85.2%的产率得到丙帕唑胺
  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

• Acetazolamide-based fungal chitinase inhibitors
  作者：Alexander W. Schüttelkopf、Ludovic Gros、David E. Blair、Julie A. Frearson、Daan M.F. van Aalten、Ian H. Gilbert

  DOI：10.1016/j.bmc.2010.09.062

  日期：2010.12

  Chitin is an essential structural component of the fungal cell wall. Chitinases are thought to be important for fungal cell wall remodelling, and inhibition of these enzymes has been proposed as a potential strategy for development of novel anti-fungals. The fungal pathogen Aspergillus fumigatus possesses two distinct multi-gene chitinase families. Here we explore acetazolamide as a chemical scaffold for the inhibition of an A. fumigatus 'plant-type' chitinase. A co-crystal structure of AfChiA1 with acetazolamide was used to guide synthesis and screening of acetazolamide analogues that yielded SAR in agreement with these structural data. Although acetazolamide and its analogues are weak inhibitors of the enzyme, they have a high ligand efficiency and as such are interesting leads for future inhibitor development.
• 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.
• Notes - Heterocyclic Sulfonamides as Carbonic Anhydrase Inhibitors. 2-Acylamido- and 2-Sulfonamido-1,3,4-thiadiazole-5-sulfonamides
  作者：J. Vaughan, Jr.、J. Eichler、G. Anderson

  DOI：10.1021/jo01112a612

  日期：1956.6
• Gostea; Iacobescu, 1958, p. 33,38
  作者：Gostea、Iacobescu

  DOI：——

  日期：——
• 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。