4-allyloxy-3-fluorobenzoic acid | 445026-40-4

• 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: 4-allyloxy-3-fluorobenzoic acid
• 英文别名: 3-Fluoro-4-(prop-2-en-1-yloxy)benzoic acid；3-fluoro-4-prop-2-enoxybenzoic acid
• CAS: 445026-40-4
• 化学式: C₁₀H₉FO₃
• 分子量: 196.178
• InChiKey: WIRVSVAMFVPXOD-UHFFFAOYSA-N

物化性质

• 沸点：
  322.7±27.0 °C(Predicted)
• 密度：
  1.239±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  14
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  46.5
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-allyloxy-3-fluorobenzoic acid 在 AtH₂⁽¹⁺⁾*HO^(1-) 、 盐酸羟胺 、 sodium methylate 、 N,N-二异丙基乙胺 、 4,4'-二氨基二苯乙烯-2,2'-二磺酸 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 作用下， 以 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 31.0h， 生成 2-(4-(allyloxy)-3-fluorophenyl)-N-hydroxy-4,5-dihydrooxazole-4-carboxamide
  参考文献：
  名称：

  Potent, Novel in Vitro Inhibitors of the Pseudomonas aeruginosa Deacetylase LpxC

  摘要：

  Deacetylation of uridyldiphospho-3-O-(R-hydroxydecanoyl)-N-acetylglucosamine by LpxC is the first committed step in the Pseudomonas aeruginosa biosynthetic pathway to lipid A; homologous enzymes are found widely among Gram-negative bacteria. As an essential enzyme for which no inhibitors have yet been reported, the P. aeruginosa LpxC represents a highly attractive target for a novel antibacterial drug. We synthesized several focused small-molecule libraries, each composed of a variable aromatic ring, one of four heterocyclic/spacer moieties, and a hydroxamic acid and evaluated the LpxC inhibition of these compounds against purified P. aeruginosa enzyme. To ensure that the in vitro assay would be as physiologically relevant as possible, we synthesized a tritiated form of the specific P. aeruginosa glycolipid substrate and measured directly the enzymatically released acetate. Several of our novel compounds, predominantly those having fluorinated substituents on the aromatic ring and an oxazoline as the heterocyclic moiety, demonstrated in vitro IC50 values less than 1 muM. We now report the synthesis and in vitro evaluation of these P. aeruginosa LpxC inhibitors.

  DOI：

  10.1021/jm010579r
• 作为产物：
  描述：

  2-氟苯酚 在 溴 、 叔丁基锂 、 potassium carbonate 作用下， 以 四氢呋喃 、 二氯甲烷 、 丙酮 、 正戊烷 为溶剂， 反应 60.25h， 生成 4-allyloxy-3-fluorobenzoic acid
  参考文献：
  名称：

  Potent, Novel in Vitro Inhibitors of the Pseudomonas aeruginosa Deacetylase LpxC

  摘要：

  Deacetylation of uridyldiphospho-3-O-(R-hydroxydecanoyl)-N-acetylglucosamine by LpxC is the first committed step in the Pseudomonas aeruginosa biosynthetic pathway to lipid A; homologous enzymes are found widely among Gram-negative bacteria. As an essential enzyme for which no inhibitors have yet been reported, the P. aeruginosa LpxC represents a highly attractive target for a novel antibacterial drug. We synthesized several focused small-molecule libraries, each composed of a variable aromatic ring, one of four heterocyclic/spacer moieties, and a hydroxamic acid and evaluated the LpxC inhibition of these compounds against purified P. aeruginosa enzyme. To ensure that the in vitro assay would be as physiologically relevant as possible, we synthesized a tritiated form of the specific P. aeruginosa glycolipid substrate and measured directly the enzymatically released acetate. Several of our novel compounds, predominantly those having fluorinated substituents on the aromatic ring and an oxazoline as the heterocyclic moiety, demonstrated in vitro IC50 values less than 1 muM. We now report the synthesis and in vitro evaluation of these P. aeruginosa LpxC inhibitors.

  DOI：

  10.1021/jm010579r

文献信息

• Potent, Novel in Vitro Inhibitors of the <i>Pseudomonas </i><i>a</i><i>eruginosa</i> Deacetylase LpxC
  作者：Toni Kline、Niels H. Andersen、Eric A. Harwood、Jason Bowman、Andre Malanda、Stephanie Endsley、Alice L. Erwin、Michael Doyle、Susan Fong、Alex L. Harris、Brian Mendelsohn、Khisimuzi Mdluli、Christian R. H. Raetz、C. Kendall Stover、Pamela R. Witte、Asha Yabannavar、Shuguang Zhu

  DOI：10.1021/jm010579r

  日期：2002.7.1

  Deacetylation of uridyldiphospho-3-O-(R-hydroxydecanoyl)-N-acetylglucosamine by LpxC is the first committed step in the Pseudomonas aeruginosa biosynthetic pathway to lipid A; homologous enzymes are found widely among Gram-negative bacteria. As an essential enzyme for which no inhibitors have yet been reported, the P. aeruginosa LpxC represents a highly attractive target for a novel antibacterial drug. We synthesized several focused small-molecule libraries, each composed of a variable aromatic ring, one of four heterocyclic/spacer moieties, and a hydroxamic acid and evaluated the LpxC inhibition of these compounds against purified P. aeruginosa enzyme. To ensure that the in vitro assay would be as physiologically relevant as possible, we synthesized a tritiated form of the specific P. aeruginosa glycolipid substrate and measured directly the enzymatically released acetate. Several of our novel compounds, predominantly those having fluorinated substituents on the aromatic ring and an oxazoline as the heterocyclic moiety, demonstrated in vitro IC50 values less than 1 muM. We now report the synthesis and in vitro evaluation of these P. aeruginosa LpxC inhibitors.