2-[2-[(1-ethyl-3,4-dihydro-2H-naphthalen-1-yl)methyl]-3,3,3-trifluoro-2-hydroxypropyl]-4-methyl-1H-indole-6-carbonitrile | 1002761-96-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 四氢化萘
• 英文名称: 2-[2-[(1-ethyl-3,4-dihydro-2H-naphthalen-1-yl)methyl]-3,3,3-trifluoro-2-hydroxypropyl]-4-methyl-1H-indole-6-carbonitrile
• CAS: 1002761-96-7
• 化学式: C₂₆H₂₇F₃N₂O
• 分子量: 440.508
• InChiKey: REOSGJSLYJEKCA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.1
• 重原子数：
  32
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  59.8
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  N-(2-bromo-5-cyano-3-methylphenyl)acetamide 、 2-[(1-ethyl-1,2,3,4-tetrahydro-1-naphthalenyl)methyl]-1,1,1-trifluoro-4-pentyn-2-ol 在 bis-triphenylphosphine-palladium(II) chloride 、 copper(l) iodide 1,1,2,3-四甲基胍 作用下， 以 1,4-二氧六环 为溶剂， 反应 18.0h， 生成 2-[2-[(1-ethyl-3,4-dihydro-2H-naphthalen-1-yl)methyl]-3,3,3-trifluoro-2-hydroxypropyl]-4-methyl-1H-indole-6-carbonitrile
  参考文献：
  名称：

  Nonsteroidal Glucocorticoid Agonists: Tetrahydronaphthalenes with Alternative Steroidal A-Ring Mimetics Possessing Dissociated (Transrepression/Transactivation) Efficacy Selectivity

  摘要：

  The synthesis and biological activity of tetrahydronaphthalene derivatives coupled to various heterocycles are described. These compounds are potent glucocorticoid receptor agonists with efficacy selectivity in an NF kappa B glucocorticoid receptor (GR) agonist assay (representing transrepression effects) over an MMTV GR agonist assay (representing transactivation effects). Quinolones, indoles, and C- and N-linked quinolines are some of the heterocycles that provide efficacy selectivity. For example, the isoquinoline 49D1E2 has NF kappa B agonism with pIC(50) of 8.66 (89%) and reduced efficacy in MMTV agonism (6%), and the quinoline 55D1E1 has NF kappa B agonism with pIC(50) of 9.30 (101%) and reduced efficacy in MMTV agonism with pEC(50) of 8.02 (47%). A description of how a compound from each class is modeled in the active site of the receptor is given.

  DOI：

  10.1021/jm070778w