1-Naphthalenepropanoic acid,1,2,3,4-tetrahydro-1-(2-methylpropyl)-a-oxo- | 872835-51-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 1-Naphthalenepropanoic acid,1,2,3,4-tetrahydro-1-(2-methylpropyl)-a-oxo-
• 英文别名: 3-(1-Isobutyl-1,2,3,4-tetrahydro-naphthalen-1-yl)-2-oxo-propionic acid
• CAS: 872835-51-3
• 化学式: C₁₇H₂₂O₃
• 分子量: 274.36
• InChiKey: PLSLWLJMLZAFPN-UHFFFAOYSA-N

物化性质

• 沸点：
  398.9±11.0 °C(Predicted)
• 密度：
  1.090±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.35
• 重原子数：
  20.0
• 可旋转键数：
  5.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  54.37
• 氢给体数：
  1.0
• 氢受体数：
  2.0

反应信息

• 作为反应物：
  描述：

  1-Naphthalenepropanoic acid,1,2,3,4-tetrahydro-1-(2-methylpropyl)-a-oxo- 在 氯化亚砜 、 cesium fluoride 作用下， 以 N,N-二甲基乙酰胺 、 N,N-二甲基甲酰胺 为溶剂， 生成 3,3,3-trifluoro-2-hydroxy-N-(4-methyl-1-oxo-1H-2,3-benzoxazin-6-yl)-2-{[1-(2-methylpropyl)-1,2,3,4-tetrahydro-1-naphthalenyl]methyl}propanamide
  参考文献：
  名称：

  Dissociated Nonsteroidal Glucocorticoid Receptor Modulators; Discovery of the Agonist Trigger in a Tetrahydronaphthalene−Benzoxazine Series

  摘要：

  The tetrahydronaphthalene-benzoxazine glucocorticoid receptor (GR) partial agonist 4b was optimized to produce potent full agonists of GR. Aromatic ring substitution of the tetrahydronaphthalene leads to weak GR antagonists. Discovery of an "agonist trigger" substituent on the saturated ring of the tetrahydronaphthalene leads to increased potency and efficacious GR agonism. These compounds are efficacy selective in an NFkB GR agonist assay ( representing transrepression effects) over an MMTV GR agonist assay ( representing transactivation effects). 52 and 60 have NFkB pIC(50) = 8.92 (105%) and 8.69 (92%) and MMTV pEC(50) = 8.20 (47%) and 7.75 (39%), respectively. The impact of the trigger substituent on agonism is modeled within GR and discussed. 36, 52, and 60 have anti-inflammatory activity in a mouse model of inflammation after topical dosing with 52 and 60, having an effect similar to that of dexamethasone. The original lead was discovered by a manual agreement docking method, and automation of this method is also described.

  DOI：

  10.1021/jm060302x
• 作为产物：
  描述：

  在 臭氧 、 二甲基硫 、 氢氧化钾 作用下， 以 甲醇 为溶剂， 生成 1-Naphthalenepropanoic acid,1,2,3,4-tetrahydro-1-(2-methylpropyl)-a-oxo-
  参考文献：
  名称：

  Dissociated Nonsteroidal Glucocorticoid Receptor Modulators; Discovery of the Agonist Trigger in a Tetrahydronaphthalene−Benzoxazine Series

  摘要：

  The tetrahydronaphthalene-benzoxazine glucocorticoid receptor (GR) partial agonist 4b was optimized to produce potent full agonists of GR. Aromatic ring substitution of the tetrahydronaphthalene leads to weak GR antagonists. Discovery of an "agonist trigger" substituent on the saturated ring of the tetrahydronaphthalene leads to increased potency and efficacious GR agonism. These compounds are efficacy selective in an NFkB GR agonist assay ( representing transrepression effects) over an MMTV GR agonist assay ( representing transactivation effects). 52 and 60 have NFkB pIC(50) = 8.92 (105%) and 8.69 (92%) and MMTV pEC(50) = 8.20 (47%) and 7.75 (39%), respectively. The impact of the trigger substituent on agonism is modeled within GR and discussed. 36, 52, and 60 have anti-inflammatory activity in a mouse model of inflammation after topical dosing with 52 and 60, having an effect similar to that of dexamethasone. The original lead was discovered by a manual agreement docking method, and automation of this method is also described.

  DOI：

  10.1021/jm060302x