(2S)-2-[6-(3,4-dihydro-2H-chromen-6-yl)-4-methyl-3-azatricyclo[9.4.0.02,7]pentadeca-1(15),2,4,6,11,13-hexaen-5-yl]-2-[(2-methylpropan-2-yl)oxy]acetic acid | 1602647-28-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并环庚烷吡啶
• 英文名称: (2S)-2-[6-(3,4-dihydro-2H-chromen-6-yl)-4-methyl-3-azatricyclo[9.4.0.02,7]pentadeca-1(15),2,4,6,11,13-hexaen-5-yl]-2-[(2-methylpropan-2-yl)oxy]acetic acid
• CAS: 1602647-28-8
• 化学式: C₃₀H₃₃NO₄
• 分子量: 471.596
• InChiKey: QXKVEBCASQUKTG-NDEPHWFRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.2
• 重原子数：
  35
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  68.6
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  [(2S)-4-(3,4-dihydro-2H-chromen-6-yl)-2-[(2-methylpropan-2-yl)oxy]but-3-ynyl] 2,2-dimethylpropanoate 在 2-氯吡啶 、 sodium chlorite 、 sodium dihydrogenphosphate 、 锂硼氢 、 3-甲基-1-环己烯 、 三氟甲磺酸酐 、 戴斯-马丁氧化剂 作用下， 以 四氢呋喃 、 异丁醇 、 水 为溶剂， 生成 (2S)-2-[6-(3,4-dihydro-2H-chromen-6-yl)-4-methyl-3-azatricyclo[9.4.0.02,7]pentadeca-1(15),2,4,6,11,13-hexaen-5-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

文献信息

• Minimizing the Contribution of Enterohepatic Recirculation to Clearance in Rat for the NCINI Class of Inhibitors of HIV
  作者：Lee D. Fader、Rebekah Carson、Sébastien Morin、François Bilodeau、Catherine Chabot、Ted Halmos、Murray D. Bailey、Stephen H. Kawai、René Coulombe、Steven Laplante、Kevork Mekhssian、Araz Jakalian、Michel Garneau、Jianmin Duan、Stephen W. Mason、Bruno Simoneau、Craig Fenwick、Youla Tsantrizos、Christiane Yoakim

  DOI：10.1021/ml500110j

  日期：2014.6.12

  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.