8-(4-hydroxy-6-methyl-2-oxo-2H-pyran-3-yl)-8-oxooctanoic acid | 117213-41-9

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 酮酸及其衍生物
• 英文名称: 8-(4-hydroxy-6-methyl-2-oxo-2H-pyran-3-yl)-8-oxooctanoic acid
• 英文别名: 8-(4-Hydroxy-6-methyl-2-oxopyran-3-yl)-8-oxooctanoic acid；8-(4-hydroxy-6-methyl-2-oxopyran-3-yl)-8-oxooctanoic acid
• CAS: 117213-41-9
• 化学式: C₁₄H₁₈O₆
• 分子量: 282.293
• InChiKey: VBYFBCFSMJXJCU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  20
• 可旋转键数：
  8
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  101
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  8-(4-hydroxy-6-methyl-2-oxo-2H-pyran-3-yl)-8-oxooctanoic acid 在 potassium peroxymonosulfate 、 草酰氯 、 三乙胺 作用下， 以 四氢呋喃 、 水 、 丙酮 、 甲苯 为溶剂， 反应 2.0h， 生成 N-(2,2-dioxido-5-oxo-4,5-dihydro-[1,2]dithiolo[4,3-b]pyrrol-6-yl)-8-(4-hydroxy-6-methyl-2-oxo-2H-pyran-3-yl)-8-oxooctanamide
  参考文献：
  名称：

  Novel Hybrid-Type Antimicrobial Agents Targeting the Switch Region of Bacterial RNA Polymerase

  摘要：

  The bacterial RNA polymerase (RNAP) is an ideal target for the development of antimicrobial agents against drug-resistant bacteria. Especially, the switch region within RNAP has been considered as an attractive binding site for drug discovery. Here, we designed and synthesized a series of novel hybrid-type inhibitors of bacterial RNAP. The antimicrobial activities were evaluated using a paper disk diffusion assay, and selected derivatives were tested to determine their MIC values. The hybrid-type antimicrobial agent 29 showed inhibitory activity against Escherichia coli RNAP. The molecular docking study suggested that the RNAP switch region would be the binding site of 29.

  DOI：

  10.1021/ml300350p
• 作为产物：
  描述：

  辛二酸单甲酯 在 4-二甲氨基吡啶 、 lithium hydroxide 、 N,N'-二异丙基碳二亚胺 作用下， 以 四氢呋喃 、 水 、 甲苯 为溶剂， 反应 23.0h， 生成 8-(4-hydroxy-6-methyl-2-oxo-2H-pyran-3-yl)-8-oxooctanoic acid
  参考文献：
  名称：

  Novel Hybrid-Type Antimicrobial Agents Targeting the Switch Region of Bacterial RNA Polymerase

  摘要：

  The bacterial RNA polymerase (RNAP) is an ideal target for the development of antimicrobial agents against drug-resistant bacteria. Especially, the switch region within RNAP has been considered as an attractive binding site for drug discovery. Here, we designed and synthesized a series of novel hybrid-type inhibitors of bacterial RNAP. The antimicrobial activities were evaluated using a paper disk diffusion assay, and selected derivatives were tested to determine their MIC values. The hybrid-type antimicrobial agent 29 showed inhibitory activity against Escherichia coli RNAP. The molecular docking study suggested that the RNAP switch region would be the binding site of 29.

  DOI：

  10.1021/ml300350p

文献信息

• Design, synthesis and biological evaluation of novel hybrids of N-aryl pyrrothine-base α-pyrone as bacterial RNA polymerase inhibitors
  作者：Xiangduan Tan、Mohan Huang、Siyun Nian、Yanfen Peng、Jianli Qin、Bo Kong、Xiaoqun Duan

  DOI：10.1016/j.bmcl.2020.127146

  日期：2020.6

  problem, thus discovery of novel and effective antibiotics is urgent. A series of novel hybrids of N-aryl pyrrothine-base α-pyrone hybrids was designed, synthesized and evaluated as bacterial RNA polymerase (RNAP) inhibitors. Among them, compound 13c exhibited potent antibacterial activity against antibiotic-resistant S. aureus with the minimum inhibitory concentration (MIC) in the range of 1-4 μg/mL

  细菌中的抗生素抗性已经成为新兴的公共卫生问题，因此迫切需要发现新型有效的抗生素。设计，合成和评估了一系列新型的N-芳基酪氨酸碱基α-吡喃酮杂种，作为细菌RNA聚合酶（RNAP）抑制剂。其中，化合物13c对抗生素耐药的金黄色葡萄球菌表现出有效的抗菌活性，最小抑制浓度（MIC）在1-4μg/ mL的范围内。此外，化合物13c对大肠杆菌RNAP表现出强的抑制活性，IC50值为16.06μM，对HepG2细胞的细胞毒性为7.04μM。分子对接研究进一步表明，化合物13c与细菌RNAP的开关区域结合。总之，化合物13c是新型细菌RNAP抑制剂，
• COOK, LUISA;TERNAI, BELA, BIOL. CHEM. HOPPE-SEYLER, 369,(1988) N 7, C. 627-631
  作者：COOK, LUISA、TERNAI, BELA

  DOI：——

  日期：——
• Novel Hybrid-Type Antimicrobial Agents Targeting the Switch Region of Bacterial RNA Polymerase
  作者：Fumika Yakushiji、Yuko Miyamoto、Yuki Kunoh、Reiko Okamoto、Hidemasa Nakaminami、Yuri Yamazaki、Norihisa Noguchi、Yoshio Hayashi

  DOI：10.1021/ml300350p

  日期：2013.2.14

  The bacterial RNA polymerase (RNAP) is an ideal target for the development of antimicrobial agents against drug-resistant bacteria. Especially, the switch region within RNAP has been considered as an attractive binding site for drug discovery. Here, we designed and synthesized a series of novel hybrid-type inhibitors of bacterial RNAP. The antimicrobial activities were evaluated using a paper disk diffusion assay, and selected derivatives were tested to determine their MIC values. The hybrid-type antimicrobial agent 29 showed inhibitory activity against Escherichia coli RNAP. The molecular docking study suggested that the RNAP switch region would be the binding site of 29.