5-bromo-2-hydroxy-3-[3-(2,3,6-trichlorophenyl)-acryloyl]benzoic acid | 1289079-61-3

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 直链 1,3-二芳基丙烷
• 英文名称: 5-bromo-2-hydroxy-3-[3-(2,3,6-trichlorophenyl)-acryloyl]benzoic acid
• 英文别名: 5-Bromo-2-hydroxy-3-[3-(2,3,6-trichlorophenyl)prop-2-enoyl]benzoic acid；5-bromo-2-hydroxy-3-[3-(2,3,6-trichlorophenyl)prop-2-enoyl]benzoic acid
• CAS: 1289079-61-3
• 化学式: C₁₆H₈BrCl₃O₄
• 分子量: 450.5
• InChiKey: OQMPYUOYAANCFA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6
• 重原子数：
  24
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  74.6
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  5-溴水杨酸 在 aluminum (III) chloride 、 硫酸 、 sodium hydroxide 作用下， 以 乙醇 、 水 为溶剂， 反应 3.33h， 生成 5-bromo-2-hydroxy-3-[3-(2,3,6-trichlorophenyl)-acryloyl]benzoic acid
  参考文献：
  名称：

  Synthesis, biological evaluation and 3D-QSAR studies of 3-keto salicylic acid chalcones and related amides as novel HIV-1 integrase inhibitors

  摘要：

  HIV-1 integrase is one of the three most important enzymes required for viral replication and is therefore an attractive target for anti retroviral therapy. We herein report the design and synthesis of 3-keto salicylic acid chalcone derivatives as novel HIV-1 integrase inhibitors. The most active compound, 5-bromo-2-hydroxy-3-[3-(2,3,6-trichlorophenyl)acryloyl] benzoic acid (25) was selectively active against integrase strand transfer, with an IC50 of 3.7 mu M. While most of the compounds exhibited strand transfer selectivity, a few were nonselective, such as 5-bromo-3-[3-(4-bromophenyl)acryloyl]-2-hydroxybenzoic acid (15), which was active against both 3'-processing and strand transfer with IC50 values of 11 +/- 4 and 5 +/- 2 mu M, respectively. The compounds also inhibited HIV replication with potencies comparable with their integrase inhibitory potencies. Thus, 5-bromo-2-hydroxy-3-[3-(2,3,6-trichlorophenyl) acryloyl] benzoic acid (25) and 5-bromo-3-[3-(4-bromophenyl) acryloyl]-2-hydroxybenzoic acid (15) inhibited HIV-1 replication with EC50 values of 7.3 and 8.7 mu M, respectively. A PHASE pharmacophore hypothesis was developed and validated by 3D-QSAR, which gave a predictive r(2) of 0.57 for an external test set of ten compounds. Phamacophore derived molecular alignments were used for CoMFA and CoMSIA 3D-QSAR modeling. CoMSIA afforded the best model with q(2) and r(2) values of 0.54 and 0.94, respectively. This model predicted all the ten compounds of the test set within 0.56 log units of the actual pIC(50) values; and can be used to guide the rational design of more potent novel 3-keto salicylic acid integrase inhibitors (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.01.047

文献信息

• Synthesis, biological evaluation and 3D-QSAR studies of 3-keto salicylic acid chalcones and related amides as novel HIV-1 integrase inhibitors
  作者：Horrick Sharma、Shivaputra Patil、Tino W. Sanchez、Nouri Neamati、Raymond F. Schinazi、John K. Buolamwini

  DOI：10.1016/j.bmc.2011.01.047

  日期：2011.3

  HIV-1 integrase is one of the three most important enzymes required for viral replication and is therefore an attractive target for anti retroviral therapy. We herein report the design and synthesis of 3-keto salicylic acid chalcone derivatives as novel HIV-1 integrase inhibitors. The most active compound, 5-bromo-2-hydroxy-3-[3-(2,3,6-trichlorophenyl)acryloyl] benzoic acid (25) was selectively active against integrase strand transfer, with an IC50 of 3.7 mu M. While most of the compounds exhibited strand transfer selectivity, a few were nonselective, such as 5-bromo-3-[3-(4-bromophenyl)acryloyl]-2-hydroxybenzoic acid (15), which was active against both 3'-processing and strand transfer with IC50 values of 11 +/- 4 and 5 +/- 2 mu M, respectively. The compounds also inhibited HIV replication with potencies comparable with their integrase inhibitory potencies. Thus, 5-bromo-2-hydroxy-3-[3-(2,3,6-trichlorophenyl) acryloyl] benzoic acid (25) and 5-bromo-3-[3-(4-bromophenyl) acryloyl]-2-hydroxybenzoic acid (15) inhibited HIV-1 replication with EC50 values of 7.3 and 8.7 mu M, respectively. A PHASE pharmacophore hypothesis was developed and validated by 3D-QSAR, which gave a predictive r(2) of 0.57 for an external test set of ten compounds. Phamacophore derived molecular alignments were used for CoMFA and CoMSIA 3D-QSAR modeling. CoMSIA afforded the best model with q(2) and r(2) values of 0.54 and 0.94, respectively. This model predicted all the ten compounds of the test set within 0.56 log units of the actual pIC(50) values; and can be used to guide the rational design of more potent novel 3-keto salicylic acid integrase inhibitors (C) 2011 Elsevier Ltd. All rights reserved.