ethyl 4-chloro-3-(pyridin-2-yl)benzoate | 1416048-24-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: ethyl 4-chloro-3-(pyridin-2-yl)benzoate
• 英文别名: Ethyl 4-chloro-3-pyridin-2-ylbenzoate；ethyl 4-chloro-3-pyridin-2-ylbenzoate
• CAS: 1416048-24-2
• 化学式: C₁₄H₁₂ClNO₂
• 分子量: 261.708
• InChiKey: ZNYJQGJWFMYHIT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  18
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  39.2
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  ethyl 4-chloro-3-(pyridin-2-yl)benzoate 在 lithium hydroxide monohydrate 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 4.0h， 以62.5%的产率得到4-chloro-3-(pyridin-2-yl)benzoic acid
  参考文献：
  名称：

  Discovery of Dap-3 Polymyxin Analogues for the Treatment of Multidrug-Resistant Gram-Negative Nosocomial Infections

  摘要：

  We report novel polymyxin analogues with improved antibacterial in vitro potency against polymprin resistant recent clinical isolates of Acinetobacter baumannii and Pseudomonas aeruginosa. In addition, a human renal cell in vitro assay (hRPTEC) was used to inform structure-toxicity relationships and further differentiate analogues. Replacement of the Dab-3 residue with a Dap-3 in combination with a relatively polar 6-oxo-1-phenyl-1,6-dihydropyridine-3-carbonyl side chain as a fatty acyl replacement yielded analogue 5x, which demonstrated an improved in vitro antimicrobial and renal cytotoxicity profiles relative to polymyxin B (PMB). However, in vivo PK/PD comparison of 5x and PMB in a murine neutropenic thigh model against P. aeruginosa strains with matched MICs showed that 5x was inferior to PMB in vivo, suggesting a lack of improved therapeutic index in spite of apparent in vitro advantages.

  DOI：

  10.1021/jm400416u
• 作为产物：
  描述：

  ethyl 3-(pyridin-2-yl)benzoate 在 叔丁基过氧化氢 、 氧气 、 氯化苄 、 palladium dichloride 作用下， 以 二甲基亚砜 为溶剂， 反应 24.0h， 生成 ethyl 4-chloro-3-(pyridin-2-yl)benzoate
  参考文献：
  名称：

  芳基甲基氯化物：钯催化2-芳基吡啶的邻位氯化和酰化的新型双功能试剂

  摘要：

  AbstractA chemoselective, palladium‐catalyzed, ligand‐directed ortho‐CH chlorination and acylation process has been developed, exhibiting high regioselectivity for 2‐arylpyridines bearing a meta‐substituent. Worthy of note is the fact that arylmethyl chlorides as new, readily available, and inexpensive reagents can selectively be utilized as chlorine or acyl sources.magnified image

  DOI：

  10.1002/adsc.201400810

文献信息

• Discovery of Dap-3 Polymyxin Analogues for the Treatment of Multidrug-Resistant Gram-Negative Nosocomial Infections
  作者：Thomas V. Magee、Matthew F. Brown、Jeremy T. Starr、David C. Ackley、Joseph A. Abramite、Jiri Aubrecht、Andrew Butler、Jared L. Crandon、Fadia Dib-Hajj、Mark E. Flanagan、Karl Granskog、Joel R. Hardink、Michael D. Huband、Rebecca Irvine、Michael Kuhn、Karen L. Leach、Bryan Li、Jian Lin、David R. Luke、Shawn H. MacVane、Alita A. Miller、Sandra McCurdy、James M. McKim、David P. Nicolau、Thuy-Trinh Nguyen、Mark C. Noe、John P. O’Donnell、Scott B. Seibel、Yue Shen、Antonia F. Stepan、Andrew P. Tomaras、Paul C. Wilga、Li Zhang、Jinfeng Xu、Jinshan Michael Chen

  DOI：10.1021/jm400416u

  日期：2013.6.27

  We report novel polymyxin analogues with improved antibacterial in vitro potency against polymprin resistant recent clinical isolates of Acinetobacter baumannii and Pseudomonas aeruginosa. In addition, a human renal cell in vitro assay (hRPTEC) was used to inform structure-toxicity relationships and further differentiate analogues. Replacement of the Dab-3 residue with a Dap-3 in combination with a relatively polar 6-oxo-1-phenyl-1,6-dihydropyridine-3-carbonyl side chain as a fatty acyl replacement yielded analogue 5x, which demonstrated an improved in vitro antimicrobial and renal cytotoxicity profiles relative to polymyxin B (PMB). However, in vivo PK/PD comparison of 5x and PMB in a murine neutropenic thigh model against P. aeruginosa strains with matched MICs showed that 5x was inferior to PMB in vivo, suggesting a lack of improved therapeutic index in spite of apparent in vitro advantages.
• Arylmethyl Chlorides: New Bifunctional Reagents for Palladium-Catalyzed<i>ortho</i>-Chlorination and Acylation of 2-Arylpyridines
  作者：Guodong Zhang、Suyan Sun、Fan Yang、Qian Zhang、Jianxun Kang、Yusheng Wu、Yangjie Wu

  DOI：10.1002/adsc.201400810

  日期：2015.2.9

  AbstractA chemoselective, palladium‐catalyzed, ligand‐directed ortho‐CH chlorination and acylation process has been developed, exhibiting high regioselectivity for 2‐arylpyridines bearing a meta‐substituent. Worthy of note is the fact that arylmethyl chlorides as new, readily available, and inexpensive reagents can selectively be utilized as chlorine or acyl sources.magnified image