(4-Ethyl-1,5-diphenyl-1H-pyrazol-3-yl)-acetic acid methyl ester | 263328-18-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: (4-Ethyl-1,5-diphenyl-1H-pyrazol-3-yl)-acetic acid methyl ester
• 英文别名: Methyl 2-(4-ethyl-1,5-diphenylpyrazol-3-yl)acetate
• CAS: 263328-18-3
• 化学式: C₂₀H₂₀N₂O₂
• 分子量: 320.391
• InChiKey: DKNGIMIYHWRHEU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  24
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  44.1
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (4-Ethyl-1,5-diphenyl-1H-pyrazol-3-yl)-acetic acid methyl ester 在 劳森试剂 、 氨 作用下， 以 甲醇 、 甲苯 为溶剂， 反应 2.0h， 生成 (4-Ethyl-1,5-diphenyl-1H-pyrazol-3-yl)-acetonitrile
  参考文献：
  名称：

  Novel 1,5-Diphenylpyrazole Nonnucleoside HIV-1 Reverse Transcriptase Inhibitors with Enhanced Activity versus the Delavirdine-Resistant P236L Mutant:  Lead Identification and SAR of 3- and 4-Substituted Derivatives

  摘要：

  Through computationally directed broad screening, a novel 1,5-diphenylpyrazole (DPP) class of HIV-1 nonnucleoside reverse transcriptase inhibitors (NNRTIs) has been discovered. Compound 2 (PNU-32945) was found to have good activity versus wild-type (IC50 = 2.3 mu M) and delavirdine-resistant P236L (IC50 = 1.1 mu M) reverse transcriptase IRT). Also, PNU-32945 has an ED50 for inhibition of viral replication in cell cultures of 0.1 mu M and was shown to be noncytotoxic with a CC50 > 10 mu M. Structure-activity relationship studies on the 3- and 4-positions of PNU-32945 led to interesting selectivity and activity within the class. In particular, the 3-hydroxyethyl-4-ethyl congener 29 is a potent inhibitor of the P236L mutant (IC50 = 0.65 mu M), whereas it is essentially inactive versus the wild-type enzyme (IC50 > 50 mu M). Furthermore, this compound was significantly more active versus the P236L mutant than delavirdine. The synthesis and RT inhibitory activity of various 3- and 4-substituted analogues are discussed.

  DOI：

  10.1021/jm990383f
• 作为产物：
  描述：

  1-苯基-1,3-丁二酮 在 甲醇 、 氨 、 sodium acetate 、 caesium carbonate 、 sodium amide 作用下， 以 甲醇 、 乙腈 、 苯 为溶剂， 反应 13.5h， 生成 (4-Ethyl-1,5-diphenyl-1H-pyrazol-3-yl)-acetic acid methyl ester
  参考文献：
  名称：

  Novel 1,5-Diphenylpyrazole Nonnucleoside HIV-1 Reverse Transcriptase Inhibitors with Enhanced Activity versus the Delavirdine-Resistant P236L Mutant:  Lead Identification and SAR of 3- and 4-Substituted Derivatives

  摘要：

  Through computationally directed broad screening, a novel 1,5-diphenylpyrazole (DPP) class of HIV-1 nonnucleoside reverse transcriptase inhibitors (NNRTIs) has been discovered. Compound 2 (PNU-32945) was found to have good activity versus wild-type (IC50 = 2.3 mu M) and delavirdine-resistant P236L (IC50 = 1.1 mu M) reverse transcriptase IRT). Also, PNU-32945 has an ED50 for inhibition of viral replication in cell cultures of 0.1 mu M and was shown to be noncytotoxic with a CC50 > 10 mu M. Structure-activity relationship studies on the 3- and 4-positions of PNU-32945 led to interesting selectivity and activity within the class. In particular, the 3-hydroxyethyl-4-ethyl congener 29 is a potent inhibitor of the P236L mutant (IC50 = 0.65 mu M), whereas it is essentially inactive versus the wild-type enzyme (IC50 > 50 mu M). Furthermore, this compound was significantly more active versus the P236L mutant than delavirdine. The synthesis and RT inhibitory activity of various 3- and 4-substituted analogues are discussed.

  DOI：

  10.1021/jm990383f