norfloxacin methanesulfonate

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: norfloxacin methanesulfonate
• 英文别名: 1-Ethyl-6-fluoro-4-oxo-7-piperazin-1-ylquinoline-3-carboxylic acid;methanesulfonic acid
• 化学式: CH₄O₃S*C₁₆H₁₈FN₃O₃
• 分子量: 415.443
• InChiKey: OQPBNMAOEATERV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.77
• 重原子数：
  28
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  136
• 氢给体数：
  3
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  norfloxacin methanesulfonate 在 1,8-双二甲氨基萘 、 三氟乙酸 作用下， 以 二氯甲烷 、 氯仿 、 N,N-二甲基甲酰胺 为溶剂， 反应 56.0h， 生成 1-ethyl-6-fluoro-1,4-dihydro-4-oxo-7-[1'-(4'-N-(succinyloxymethyleneoxycarbonyl)piperazinyl)]-3-quinolinecarboxylic acid
  参考文献：
  名称：

  Synthesis and Activities of Pyoverdin−Quinolone Adducts: A Prospective Approach to a Specific Therapy Against Pseudomonas aeruginosa

  摘要：

  Pseudomonas aeruginosa is particularly resistant to most all the antibiotics presently available, essentially because of the very low permeability of its outer membrane. To overcome this, we synthesized four siderophore-based antibiotics formed by two quinolones - norfloxacin and benzonaphthyridone - bound to the pyoverdin of P. aeruginosa ATCC 15692 via two types of spacer arms: one stable and the other readily hydrolyzable. From the comparison of their antibacterial properties with those of the two unbound quinolones, we reached the following conclusions: (a) The adducts inhibit Escherichia: coli's gyrase showing that the dissociation of the compounds is not necessary for their activity. However, the presence of the pyoverdin moiety on the molecule decreases the inhibition activity compared to the antibiotic alone. (b) They facilitate the uptake of Fe-55 using the specific pyoverdin-mediated iron-transport system of the bacterium. No uptake was observed either with II? aeruginosa ATCC 27853, which produces a structurally different pyoverdin, or with P. aeruginosa K690, which is a mutant of P. aeruginosa ATCC 15692 lacking FpvA, the outer-membrane pyoverdin receptor. (c) MIC determinations have shown that only strains P. aeruginosa ATCC 15692 and the derived outer-membrane receptor-producing but pyoverdin-deficient P. aeruginosa IA1 mutant present higher susceptibility to the pyoverdin-quinolone adducts, whereas P. aeruginosa ATCC 27853 and K690 are much more resistant. (d) Growth inhibition by these adducts confirmed these results and showed that the adducts with the hydrolyzable spacer arm have better activity than those with the stable one and that the labile spacer arm adducts present much higher activity than the quinolones alone. These results show clearly that the penetration of the antibiotic into the cells is favored when this latter is coupled with pyoverdin: Only the strains possessing the appropriate outer-membrane receptor present higher susceptibility to the adduct. In this case the antibiotic uses the pyoverdin-mediated iron-transport system. Furthermore, better efficiency is obtained when the spacer arm is liabile and favors the antibiotic release inside the cell, allowing better inhibition of gyrase.

  DOI：

  10.1021/jm990508g
• 作为产物：
  描述：

  甲烷磺酸 、 诺氟沙星 以 乙腈 为溶剂， 生成 norfloxacin methanesulfonate
  参考文献：
  名称：

  诺氟沙星的新型水合物和无水共晶/盐及其理化性质

  摘要：

  研究了生物药剂学分类系统 BCS IV 类抗生素药物诺氟沙星 (NORF) 的低溶解度和低渗透性，以改善水合和无水共晶的理化性质/NORF 与对羟基苯甲酸甲酯 (MBZ)、对羟基苯甲酸乙酯、甲磺酸 (MSA)、苯磺酸 (BSA)、对甲苯磺酸 (PTSA) 和酪胺 (TYM) 形成的盐。这些结晶形式的特征在于粉末 X 射线衍射 (PXRD)、热 [差示扫描量热法 (DSC)]、重量分析 [热重分析 (TGA)]、光谱 [红外 (IR)] 和显微镜 [扫描电子显微镜 (SEM) )] 技巧。通过单晶 X 射线衍射分析了 NORF-MBZ-HYD、NORF-MSA-HYD、NORF-PTSA 和 NORF-TYM-HYD 的晶体结构。此外，通过 IR、DSC 和 TGA 表征水合和无水形式，以了解水合和脱水事件，并通过场发射 SEM 表征晶体形态和形状/尺寸特征。溶解度、溶出度、和扩散测量表明，NORF

  DOI：

  10.1021/acs.cgd.3c00023

文献信息

• Synthesis and Activities of Pyoverdin−Quinolone Adducts: A Prospective Approach to a Specific Therapy Against <i>Pseudomonas a</i><i>eruginosa</i>
  作者：Christophe Hennard、Que Chi Truong、Jean-François Desnottes、Jean-Marc Paris、Nicole J. Moreau、Mohamed A. Abdallah

  DOI：10.1021/jm990508g

  日期：2001.6.1

  Pseudomonas aeruginosa is particularly resistant to most all the antibiotics presently available, essentially because of the very low permeability of its outer membrane. To overcome this, we synthesized four siderophore-based antibiotics formed by two quinolones - norfloxacin and benzonaphthyridone - bound to the pyoverdin of P. aeruginosa ATCC 15692 via two types of spacer arms: one stable and the other readily hydrolyzable. From the comparison of their antibacterial properties with those of the two unbound quinolones, we reached the following conclusions: (a) The adducts inhibit Escherichia: coli's gyrase showing that the dissociation of the compounds is not necessary for their activity. However, the presence of the pyoverdin moiety on the molecule decreases the inhibition activity compared to the antibiotic alone. (b) They facilitate the uptake of Fe-55 using the specific pyoverdin-mediated iron-transport system of the bacterium. No uptake was observed either with II? aeruginosa ATCC 27853, which produces a structurally different pyoverdin, or with P. aeruginosa K690, which is a mutant of P. aeruginosa ATCC 15692 lacking FpvA, the outer-membrane pyoverdin receptor. (c) MIC determinations have shown that only strains P. aeruginosa ATCC 15692 and the derived outer-membrane receptor-producing but pyoverdin-deficient P. aeruginosa IA1 mutant present higher susceptibility to the pyoverdin-quinolone adducts, whereas P. aeruginosa ATCC 27853 and K690 are much more resistant. (d) Growth inhibition by these adducts confirmed these results and showed that the adducts with the hydrolyzable spacer arm have better activity than those with the stable one and that the labile spacer arm adducts present much higher activity than the quinolones alone. These results show clearly that the penetration of the antibiotic into the cells is favored when this latter is coupled with pyoverdin: Only the strains possessing the appropriate outer-membrane receptor present higher susceptibility to the adduct. In this case the antibiotic uses the pyoverdin-mediated iron-transport system. Furthermore, better efficiency is obtained when the spacer arm is liabile and favors the antibiotic release inside the cell, allowing better inhibition of gyrase.
• Novel Hydrate and Anhydrate Cocrystals/Salts of Norfloxacin and Their Physicochemical Properties
  作者：Anilkumar Gunnam、Ashwini K. Nangia

  DOI：10.1021/acs.cgd.3c00023

  日期：2023.6.7

  The low solubility and low permeability of Biopharmaceutics Classification System BCS class IV antibiotic drug norfloxacin (NORF) were studied for improvement of physicochemical properties in hydrated and anhydrous cocrystals/salts of NORF with methyl paraben (MBZ), ethyl paraben, methanesulfonic acid (MSA), benzenesulfonic acid (BSA), p-toluenesulfonic acid (PTSA), and tyramine (TYM). These crystalline

  研究了生物药剂学分类系统 BCS IV 类抗生素药物诺氟沙星 (NORF) 的低溶解度和低渗透性，以改善水合和无水共晶的理化性质/NORF 与对羟基苯甲酸甲酯 (MBZ)、对羟基苯甲酸乙酯、甲磺酸 (MSA)、苯磺酸 (BSA)、对甲苯磺酸 (PTSA) 和酪胺 (TYM) 形成的盐。这些结晶形式的特征在于粉末 X 射线衍射 (PXRD)、热 [差示扫描量热法 (DSC)]、重量分析 [热重分析 (TGA)]、光谱 [红外 (IR)] 和显微镜 [扫描电子显微镜 (SEM) )] 技巧。通过单晶 X 射线衍射分析了 NORF-MBZ-HYD、NORF-MSA-HYD、NORF-PTSA 和 NORF-TYM-HYD 的晶体结构。此外，通过 IR、DSC 和 TGA 表征水合和无水形式，以了解水合和脱水事件，并通过场发射 SEM 表征晶体形态和形状/尺寸特征。溶解度、溶出度、和扩散测量表明，NORF