propyl 1-cyclopropyl-6-fluoro-4-oxo-7-(piperazin-1-yl)-1,4-dihydroquinoline-3-carboxylate | 1239881-81-2

• 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: propyl 1-cyclopropyl-6-fluoro-4-oxo-7-(piperazin-1-yl)-1,4-dihydroquinoline-3-carboxylate
• 英文别名: n-propyl 1-cyclopropyl-6-fluoro-4-oxo-7-piperazin-1-yl-1,4-dihydroquinoline-3-carboxylate；ciprofloxacin n-propyl ester；Propyl 1-cyclopropyl-6-fluoro-4-oxo-7-piperazin-1-ylquinoline-3-carboxylate；propyl 1-cyclopropyl-6-fluoro-4-oxo-7-piperazin-1-ylquinoline-3-carboxylate
• CAS: 1239881-81-2
• 化学式: C₂₀H₂₄FN₃O₃
• 分子量: 373.427
• InChiKey: VKUDGLSPCRRLLQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  27
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  61.9
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  7-(4-(tert-butoxycarbonyl)piperazin-1-yl)-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydroquinoline-3-carboxylic acid 在 4-二甲氨基吡啶 、 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 生成 propyl 1-cyclopropyl-6-fluoro-4-oxo-7-(piperazin-1-yl)-1,4-dihydroquinoline-3-carboxylate
  参考文献：
  名称：

  Optimizing Solubility and Permeability of a Biopharmaceutics Classification System (BCS) Class 4 Antibiotic Drug Using Lipophilic Fragments Disturbing the Crystal Lattice

  摘要：

  Esterification was used to simultaneously increase solubility and permeability of ciprofloxacin, a biopharmaceutics classification system (BCS) class 4 drug (low solubility/low permeability) with solid-state limited solubility. Molecular flexibility was increased to disturb the crystal lattice, lower the melting point, and thereby improve the solubility, whereas lipophilicity was increased to enhance the intestinal permeability. These structural changes resulted in BCS class 1 analogues (high solubility/high permeability) emphasizing that simple medicinal chemistry may improve both these properties.

  DOI：

  10.1021/jm301721e

文献信息

• Design of Ciprofloxacin Derivatives that Inhibit Growth of Methicillin Resistant Staphylococcus aureus (MRSA) and Methicillin Susceptible Staphylococcus aureus (MSSA)
  作者：Ronald Bartzatt、Suat L.G. Cirillo、Jeffrey D. Cirillo

  DOI：10.2174/157340610791321442

  日期：2010.3.1

  Three derivatives of ciprofloxacin (compound B, C, and D) were constructed utilizing microwave synthesis methodology (compound D) or diazoalkane reaction in nonaqueous solvent (compounds B and C). The final structures of the derivatives featured an ester group in place of the original carboxyl group of the ciprofloxacin. These ester groups contained aliphatic single carbon (compound B), two carbon length (compound C), or three carbon length propyl ester group (compound D). The ester groups strongly affected the molecular properties of the parent ciprofloxacin. As the size of the ester group increased the formula weight, molar volume, and number of rotatable bonds increased. The Log P for these compounds were -0.701, -0.441, -0.065, 0.437 for ciprofloxacin, B, C, and compound D, respectively. Numerical values of dermal permeability coefficient (Kp) increased rapidly as length of the ester carbon chain increased. The immediate consequence of Kp increase is an increased skin penetration rate based on dose and time span of administration. Polar surface area for ciprofloxacin is 74.569 Angstroms2, but decreases to 63.575 Angstroms2 for all three derivatives. All three derivatives of ciprofloxacin showed zero violations of the Rule of 5, indicating these drugs would have favorable bioavailability. Compounds A, B, C, and D were placed into tissue culture with methicillin resistant and susceptible Staphylococcus aureus (MRSA and MSSA, respectively) to determine levels of bacterial growth inhibition. All compounds induced greater than 60 % inhibition of MSSA at concentrations as low as 15.63 micrograms/milliliter. All four compounds induced greater than 80 % inhibition of MRSA at concentratins as low as 15.63 micrograms/milliliter. Development of novel drug designs will benefit the clinical treatment of dangerous infections of MSSA and MRSA.

  利用微波合成法（化合物D）或非水溶剂中的重氮甲烷反应（化合物B和C）合成了三种环丙沙星衍生物（化合物B、C和D）。衍生物的最终结构中，环丙沙星原有的羧基被酯基替代。这些酯基包含烷基单碳（化合物B）、双碳长度（化合物C）或三碳长度的丙酯基（化合物D）。酯基显著影响了环丙沙星母体的分子性质。随着酯基尺寸的增大，其分子量、摩尔体积和可旋转键的数量也随之增加。这些化合物的Log P值分别为环丙沙星的-0.701、B的-0.441、C的-0.065和化合物D的0.437。随着酯碳链长度的增加，透皮渗透系数（Kp）数值迅速增大。Kp增大的直接后果是基于剂量和给药时间间隔的皮肤渗透速率增加。环丙沙星的极性表面积为74.569平方埃，而三种衍生物的值降至63.575平方埃。所有三种环丙沙星衍生物均未违反五规则，表明这些药物将具有良好的生物利用度。将化合物A、B、C和D与耐甲氧西林和敏感的金黄色葡萄球菌（MRSA和MSSA）进行组织培养，以确定细菌生长抑制水平。所有化合物在低至15.63微克/毫升的浓度下对MSSA的抑制率均超过60%。所有四种化合物在低至15.63微克/毫升的浓度下对MRSA的抑制率均超过80%。开发新型药物设计将有利于临床治疗危险的MSSA和MRSA感染。
• Optimizing Solubility and Permeability of a Biopharmaceutics Classification System (BCS) Class 4 Antibiotic Drug Using Lipophilic Fragments Disturbing the Crystal Lattice
  作者：Ulrika Tehler、Jonas H. Fagerberg、Richard Svensson、Mats Larhed、Per Artursson、Christel A. S. Bergström

  DOI：10.1021/jm301721e

  日期：2013.3.28

  Esterification was used to simultaneously increase solubility and permeability of ciprofloxacin, a biopharmaceutics classification system (BCS) class 4 drug (low solubility/low permeability) with solid-state limited solubility. Molecular flexibility was increased to disturb the crystal lattice, lower the melting point, and thereby improve the solubility, whereas lipophilicity was increased to enhance the intestinal permeability. These structural changes resulted in BCS class 1 analogues (high solubility/high permeability) emphasizing that simple medicinal chemistry may improve both these properties.