methyl 5-bromo-2-methoxybiphenyl-3-carboxylate | 1155261-82-7

• 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: methyl 5-bromo-2-methoxybiphenyl-3-carboxylate
• 英文别名: Methyl 5-bromo-2-methoxy-3-phenylbenzoate
• CAS: 1155261-82-7
• 化学式: C₁₅H₁₃BrO₃
• 分子量: 321.17
• InChiKey: HUPTVWGJLMDZDF-UHFFFAOYSA-N

物化性质

• 沸点：
  389.3±42.0 °C(Predicted)
• 密度：
  1.379±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  19
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.13
• 拓扑面积：
  35.5
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  methyl 5-bromo-2-methoxybiphenyl-3-carboxylate 在 三溴化硼 作用下， 以 二氯甲烷 为溶剂， 以57%的产率得到3-phenyl-5-bromosalicylic acid
  参考文献：
  名称：

  Structure-Guided Design, Synthesis, and Evaluation of Salicylic Acid-Based Inhibitors Targeting a Selectivity Pocket in the Active Site of Human 20α-Hydroxysteroid Dehydrogenase (AKR1C1)

  摘要：

  The first design, synthesis, and evaluation of human 20(x-hydroxysteroid dehydrogenase (AKR1C1) inhibitors based on the recently published crystal structure of its ternary complex with inhibitor are reported. While the enzyme-inhibitor interactions observed in the crystal structure remain conserved with the newly designed inhibitors, the additional phenyl group of the most potent compound, 3-bromo-5-phenylsalicylic acid, targets a nonconserved hydrophobic pocket in the active site of AKR1C1 resulting in 21-fold improved potency (K(i) = 4 nM) over the structurally similar 3 alpha-hydroxysteroid dehydrogenase isoform (AKR1C2). The compound is hydrogen bonded to Tyr55, His 117, and His222, and the phenyl ring forms additional van der Waals interactions with residues Leu308, Phe311, and the nonconserved Leu54 (Val in AKR1C2). Additionally, the metabolism of progesterone in AKR1C1-overexpressed cells was potently inhibited by 3-bromo-5-phenylsalicylic acid, which was effective from 10 nM with an IC(50) value equal to 460 nM.

  DOI：

  10.1021/jm9001633
• 作为产物：
  描述：

  methyl 2-methoxy-3-iodo-5-bromobenzoate 、 苯硼酸 在 potassium phosphate 、 四(三苯基膦)钯 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以89%的产率得到methyl 5-bromo-2-methoxybiphenyl-3-carboxylate
  参考文献：
  名称：

  Structure-Guided Design, Synthesis, and Evaluation of Salicylic Acid-Based Inhibitors Targeting a Selectivity Pocket in the Active Site of Human 20α-Hydroxysteroid Dehydrogenase (AKR1C1)

  摘要：

  The first design, synthesis, and evaluation of human 20(x-hydroxysteroid dehydrogenase (AKR1C1) inhibitors based on the recently published crystal structure of its ternary complex with inhibitor are reported. While the enzyme-inhibitor interactions observed in the crystal structure remain conserved with the newly designed inhibitors, the additional phenyl group of the most potent compound, 3-bromo-5-phenylsalicylic acid, targets a nonconserved hydrophobic pocket in the active site of AKR1C1 resulting in 21-fold improved potency (K(i) = 4 nM) over the structurally similar 3 alpha-hydroxysteroid dehydrogenase isoform (AKR1C2). The compound is hydrogen bonded to Tyr55, His 117, and His222, and the phenyl ring forms additional van der Waals interactions with residues Leu308, Phe311, and the nonconserved Leu54 (Val in AKR1C2). Additionally, the metabolism of progesterone in AKR1C1-overexpressed cells was potently inhibited by 3-bromo-5-phenylsalicylic acid, which was effective from 10 nM with an IC(50) value equal to 460 nM.

  DOI：

  10.1021/jm9001633

文献信息

• Structure-Guided Design, Synthesis, and Evaluation of Salicylic Acid-Based Inhibitors Targeting a Selectivity Pocket in the Active Site of Human 20α-Hydroxysteroid Dehydrogenase (AKR1C1)
  作者：Ossama El-Kabbani、Peter J. Scammells、Joshua Gosling、Urmi Dhagat、Satoshi Endo、Toshiyuki Matsunaga、Midori Soda、Akira Hara

  DOI：10.1021/jm9001633

  日期：2009.5.28

  The first design, synthesis, and evaluation of human 20(x-hydroxysteroid dehydrogenase (AKR1C1) inhibitors based on the recently published crystal structure of its ternary complex with inhibitor are reported. While the enzyme-inhibitor interactions observed in the crystal structure remain conserved with the newly designed inhibitors, the additional phenyl group of the most potent compound, 3-bromo-5-phenylsalicylic acid, targets a nonconserved hydrophobic pocket in the active site of AKR1C1 resulting in 21-fold improved potency (K(i) = 4 nM) over the structurally similar 3 alpha-hydroxysteroid dehydrogenase isoform (AKR1C2). The compound is hydrogen bonded to Tyr55, His 117, and His222, and the phenyl ring forms additional van der Waals interactions with residues Leu308, Phe311, and the nonconserved Leu54 (Val in AKR1C2). Additionally, the metabolism of progesterone in AKR1C1-overexpressed cells was potently inhibited by 3-bromo-5-phenylsalicylic acid, which was effective from 10 nM with an IC(50) value equal to 460 nM.