[(1R)-1-[(2Z,3S)-2-(2-ethoxy-2-oxoethylidene)-4-oxoazetidin-3-yl]ethyl] 3,4,5-tris(phenylmethoxy)benzoate | 868083-06-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: [(1R)-1-[(2Z,3S)-2-(2-ethoxy-2-oxoethylidene)-4-oxoazetidin-3-yl]ethyl] 3,4,5-tris(phenylmethoxy)benzoate
• CAS: 868083-06-1
• 化学式: C₃₇H₃₅NO₈
• 分子量: 621.687
• InChiKey: WKPXLDDHMQJDCW-ATGDLALPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6
• 重原子数：
  46
• 可旋转键数：
  16
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  109
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  [(1R)-1-[(2Z,3S)-2-(2-ethoxy-2-oxoethylidene)-4-oxoazetidin-3-yl]ethyl] 3,4,5-tris(phenylmethoxy)benzoate 在 palladium on activated charcoal 氢气 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 以100%的产率得到[(1R)-1-[(2Z,3S)-2-(2-ethoxy-2-oxoethylidene)-4-oxoazetidin-3-yl]ethyl] 3,4,5-trihydroxybenzoate
  参考文献：
  名称：

  4-亚烷基-β-内酰胺的设计，合成和生物学评估：对抗药性细菌具有有前途的抗生素活性的新产品。

  摘要：

  据报道4-亚烷基-氮杂环丁烷-2-酮作为新型抗多药耐药病原体的抗菌剂的设计，合成和抗菌活性。从4-乙酰氧基-氮杂环丁烷酮和重氮酯开始，可以使用原始方案轻松获得4-炔基-氮杂环丁烷-2-酮。进一步详细阐述了母体化合物，以获得一个小型的4-亚烷基衍生物库。使用基于VRS概念的GRID描述符的分子建模方法可识别出有吸引力的药物候选物，并有助于QSAR中官能团效应的合理化。通过确定其最低抑菌浓度（MIC），评估了新药对43种近期对抗生素敏感和耐药的革兰氏阳性和革兰氏阴性病原体临床分离株的体外抗菌活性。活性最高的化合物对某些测试细菌的MIC值为0.25至32 mg / L。有趣的是，一些化合物对金黄色葡萄球菌对甲氧西林敏感和耐药的菌株表现出相似的活性，表明这些试剂的可能替代作用机制是由细胞毒性和初步扫描电子显微镜研究支持的。

  DOI：

  10.1021/jm0580510
• 作为产物：
  描述：

  ethyl {(2E,3S)-3-[(1R)-(tert-butyldimethylsilanyloxy)ethyl]-4-oxoazetidin-2-ylidene}acetate 在 盐酸 、 四氯化锡 作用下， 以 乙腈 、 苯 为溶剂， 反应 4.0h， 生成 [(1R)-1-[(2Z,3S)-2-(2-ethoxy-2-oxoethylidene)-4-oxoazetidin-3-yl]ethyl] 3,4,5-tris(phenylmethoxy)benzoate
  参考文献：
  名称：

  4-Alkyliden-β-lactams conjugated to polyphenols: Synthesis and inhibitory activity

  摘要：

  A series of compounds combining the beta-lactain and polyphenol scaffold have been prepared and evaluated for inhibition of human leukocyte elastase and matrix metallo-proteases MMP-2 and MMP-9. The design of these compounds has been based on the 'overlapping-type' strategy where two pharmacophores are linked in a single molecule. The most powerful compound against elastase was an N-galloyl-4-alkyliden beta-lactam, [3-[1-(tert-butyl-dimethyl-silanyloxy)-ethyl]-4-oxo-1-(3,4,5-tris-benzyloxy-benzoyl)-azetidin-2-ylidene]-acetic acid ethylester, with an IC50 of 0.5 mu M; while the most powerful against MMP-2 was a 4-alkyliden beta-lactam arylated on the C-3 hydroxy side chain (3,5-bis-benzyloxy-4-hydroxy-benzoic acid 1-(2-benzyloxycarbonylmethylene4-oxo-azetidin-3-yl)-ethyl ester) with an IC50 of 4 mu M. Of the total 35 compounds tested, high levels of inhibition of elastase and of MMPs were separately exerted by distinct molecules. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2005.06.041

文献信息

• 4-Alkyliden-β-lactams conjugated to polyphenols: Synthesis and inhibitory activity
  作者：Gianfranco Cainelli、Paola Galletti、Spiridione Garbisa、Daria Giacomini、Luigi Sartor、Arianna Quintavalla

  DOI：10.1016/j.bmc.2005.06.041

  日期：2005.11

  A series of compounds combining the beta-lactain and polyphenol scaffold have been prepared and evaluated for inhibition of human leukocyte elastase and matrix metallo-proteases MMP-2 and MMP-9. The design of these compounds has been based on the 'overlapping-type' strategy where two pharmacophores are linked in a single molecule. The most powerful compound against elastase was an N-galloyl-4-alkyliden beta-lactam, [3-[1-(tert-butyl-dimethyl-silanyloxy)-ethyl]-4-oxo-1-(3,4,5-tris-benzyloxy-benzoyl)-azetidin-2-ylidene]-acetic acid ethylester, with an IC50 of 0.5 mu M; while the most powerful against MMP-2 was a 4-alkyliden beta-lactam arylated on the C-3 hydroxy side chain (3,5-bis-benzyloxy-4-hydroxy-benzoic acid 1-(2-benzyloxycarbonylmethylene4-oxo-azetidin-3-yl)-ethyl ester) with an IC50 of 4 mu M. Of the total 35 compounds tested, high levels of inhibition of elastase and of MMPs were separately exerted by distinct molecules. (c) 2005 Elsevier Ltd. All rights reserved.
• Design, Synthesis, and Biological Evaluation of 4-Alkyliden-beta Lactams:  New Products with Promising Antibiotic Activity Against Resistant Bacteria
  作者：Francesco Broccolo、Gianfranco Cainelli、Gianluigi Caltabiano、Clementina E. A. Cocuzza、Cosimo G. Fortuna、Paola Galletti、Daria Giacomini、Giuseppe Musumarra、Rosario Musumeci、Arianna Quintavalla

  DOI：10.1021/jm0580510

  日期：2006.5.1

  The design, synthesis, and antibacterial activity of 4-alkyliden-azetidin-2-ones as new antimicrobial agents against multidrug-resistant pathogens is reported. 4-Alkyliden-azetidin-2-ones were easily obtained using an original protocol starting from 4-acetoxy-azetidinones and diazoesters. Parent compounds were further elaborated to obtain a small library of 4-alkylidene derivatives. A molecular modeling

  据报道4-亚烷基-氮杂环丁烷-2-酮作为新型抗多药耐药病原体的抗菌剂的设计，合成和抗菌活性。从4-乙酰氧基-氮杂环丁烷酮和重氮酯开始，可以使用原始方案轻松获得4-炔基-氮杂环丁烷-2-酮。进一步详细阐述了母体化合物，以获得一个小型的4-亚烷基衍生物库。使用基于VRS概念的GRID描述符的分子建模方法可识别出有吸引力的药物候选物，并有助于QSAR中官能团效应的合理化。通过确定其最低抑菌浓度（MIC），评估了新药对43种近期对抗生素敏感和耐药的革兰氏阳性和革兰氏阴性病原体临床分离株的体外抗菌活性。活性最高的化合物对某些测试细菌的MIC值为0.25至32 mg / L。有趣的是，一些化合物对金黄色葡萄球菌对甲氧西林敏感和耐药的菌株表现出相似的活性，表明这些试剂的可能替代作用机制是由细胞毒性和初步扫描电子显微镜研究支持的。