isopropyl 4-formyl-1H-pyrrole-2-carboxylate | 273382-44-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯
• 英文名称: isopropyl 4-formyl-1H-pyrrole-2-carboxylate
• 英文别名: propan-2-yl 4-formyl-1H-pyrrole-2-carboxylate
• CAS: 273382-44-8
• 化学式: C₉H₁₁NO₃
• 分子量: 181.191
• InChiKey: DFNBDQKODMYJMB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  13
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  59.2
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  isopropyl 4-formyl-1H-pyrrole-2-carboxylate 在 sodium tetrahydroborate 、 18-冠醚-6 、 potassium tert-butylate 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 2.0h， 生成 1-(5-Chloro-2-nitro-benzenesulfonyl)-4-hydroxymethyl-1H-pyrrole-2-carboxylic acid isopropyl ester
  参考文献：
  名称：

  Structure-Based Design, Synthesis, and Biological Evaluation of Novel Pyrrolyl Aryl Sulfones:  HIV-1 Non-Nucleoside Reverse Transcriptase Inhibitors Active at Nanomolar Concentrations

  摘要：

  Pyrrolyl aryl sulfones (PASs) have been recently reported as a new class of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) inhibitors acting at the non-nucleosicie binding site of this enzyme (Artico, M.; et al. J. Med. Chem. 1996, 39, 522-530). Compound 3, the most patent inhibitor within the series (EC50 = 0.14 mu M, IC50 = 0.4 mu M, and SI > 1429), was then selected as a lead compound for a synthetic project based on molecular modeling studies. Using the three-dimensional structure of RT cocrystallized with the alpha-APA derivative R95845, we derived a model of the RT/3 complex by taking into account previously developed structure-activity relationships. Inspection of this model and docking calculations on virtual compounds prompted the design of novel PAS derivatives and related analogues. Our computational approach proved to be effective in making qualitative predictions, that is in discriminating active versus inactive compounds. Among the compounds synthesized and tested, 20 was the most active one, with EC50 = 0.045 mu M, IC50 = 0.05 mu M, and SI = 5333. Compared with the lead 3, these values represent a 3- and 8-fold improvement in the cell-based and enzyme assays, respectively, together with the highest selectivity achieved so far in the PAS series.

  DOI：

  10.1021/jm9901125
• 作为产物：
  描述：

  1,1-二氯甲醚 、 isopropyl pyrrole-2-carboxylate 在 三氯化铝 作用下， 以 1,2-二氯乙烷 为溶剂， 以50%的产率得到isopropyl 4-formyl-1H-pyrrole-2-carboxylate
  参考文献：
  名称：

  Structure-Based Design, Synthesis, and Biological Evaluation of Novel Pyrrolyl Aryl Sulfones:  HIV-1 Non-Nucleoside Reverse Transcriptase Inhibitors Active at Nanomolar Concentrations

  摘要：

  Pyrrolyl aryl sulfones (PASs) have been recently reported as a new class of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) inhibitors acting at the non-nucleosicie binding site of this enzyme (Artico, M.; et al. J. Med. Chem. 1996, 39, 522-530). Compound 3, the most patent inhibitor within the series (EC50 = 0.14 mu M, IC50 = 0.4 mu M, and SI > 1429), was then selected as a lead compound for a synthetic project based on molecular modeling studies. Using the three-dimensional structure of RT cocrystallized with the alpha-APA derivative R95845, we derived a model of the RT/3 complex by taking into account previously developed structure-activity relationships. Inspection of this model and docking calculations on virtual compounds prompted the design of novel PAS derivatives and related analogues. Our computational approach proved to be effective in making qualitative predictions, that is in discriminating active versus inactive compounds. Among the compounds synthesized and tested, 20 was the most active one, with EC50 = 0.045 mu M, IC50 = 0.05 mu M, and SI = 5333. Compared with the lead 3, these values represent a 3- and 8-fold improvement in the cell-based and enzyme assays, respectively, together with the highest selectivity achieved so far in the PAS series.

  DOI：

  10.1021/jm9901125