| 1638143-64-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• CAS: 1638143-64-2
• 化学式: C₃₂H₃₇N₃O₃
• 分子量: 511.664
• InChiKey: WNHLLYJQHZZOCY-MUUNZHRXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.61
• 重原子数：
  38.0
• 可旋转键数：
  6.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  69.4
• 氢给体数：
  1.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  在 sodium chlorite 、 sodium dihydrogenphosphate 、 3-甲基-1-环己烯 、 戴斯-马丁氧化剂 作用下， 以 异丁醇 、 水 为溶剂， 生成 (2S)-2-[4-(3,4-dihydro-2H-chromen-6-yl)-2,5-dimethyl-6-[3-(1-methylpyrazol-4-yl)phenyl]pyridin-3-yl]-2-[(2-methylpropan-2-yl)oxy]acetic acid
  参考文献：
  名称：

  Minimizing the Contribution of Enterohepatic Recirculation to Clearance in Rat for the NCINI Class of Inhibitors of HIV

  摘要：

  A scaffold replacement approach was used to identifying the pyridine series of noncatalytic site integrase inhibitors. These molecules bind with higher affinity to a tetrameric form compared to a dimeric form of integrase. Optimization of the C6 and C4 positions revealed that viruses harboring T124 or A124 amino acid substitutions are highly susceptible to these inhibitors, but viruses having the N124 amino acid substitution are about 100-fold less susceptible. Compound 20 had EC50 values <10 nM against viruses having 1 T124 or A124 substitutions in IN and >800 nM in viruses having N124 substitions. Compound 20 had an excellent in vitro ADME profile and demonstrated reduced contribution of biliary excretion to in vivo clearance compared to BI 224436, the lead compound from the quinoline series of NCINIs.

  DOI：

  10.1021/ml500110j
• 作为产物：
  描述：

  [(2S)-2-[(2-methylpropan-2-yl)oxy]but-3-ynyl] 2,2-dimethylpropanoate 在 2-氯吡啶 、 锂硼氢 、 四(三苯基膦)钯 、 三氟甲磺酸酐 、 二乙胺 作用下， 以 四氢呋喃 为溶剂， 生成
  参考文献：
  名称：

  Minimizing the Contribution of Enterohepatic Recirculation to Clearance in Rat for the NCINI Class of Inhibitors of HIV

  摘要：

  A scaffold replacement approach was used to identifying the pyridine series of noncatalytic site integrase inhibitors. These molecules bind with higher affinity to a tetrameric form compared to a dimeric form of integrase. Optimization of the C6 and C4 positions revealed that viruses harboring T124 or A124 amino acid substitutions are highly susceptible to these inhibitors, but viruses having the N124 amino acid substitution are about 100-fold less susceptible. Compound 20 had EC50 values <10 nM against viruses having 1 T124 or A124 substitutions in IN and >800 nM in viruses having N124 substitions. Compound 20 had an excellent in vitro ADME profile and demonstrated reduced contribution of biliary excretion to in vivo clearance compared to BI 224436, the lead compound from the quinoline series of NCINIs.

  DOI：

  10.1021/ml500110j