1,1,1-trifluoro-4-methyl-4-(3-fluorophenyl)pentan-2-one | 1245526-86-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 1,1,1-trifluoro-4-methyl-4-(3-fluorophenyl)pentan-2-one
• 英文别名: 1,1,1-Trifluoro-4-(3-fluorophenyl)-4-methylpentan-2-one
• CAS: 1245526-86-6
• 化学式: C₁₂H₁₂F₄O
• 分子量: 248.22
• InChiKey: ZWHBEQJRESIWGY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  17
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  17.1
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  1,1,1-trifluoro-4-methyl-4-(3-fluorophenyl)pentan-2-one 在 bis-triphenylphosphine-palladium(II) chloride 、 copper(l) iodide 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 三乙胺 作用下， 以 甲醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 16.0h， 生成 1,1,1-trifluoro-4-(3-fluorophenyl)-4-methyl-2-[(5-morpholin-4-yl-1H-pyrrolo[2,3-c]pyridin-2-yl)methyl]pentan-2-ol
  参考文献：
  名称：

  Optimization of Drug-Like Properties of Nonsteroidal Glucocorticoid Mimetics and Identification of a Clinical Candidate

  摘要：

  A series of nonsteroidal dissociated glucocorticoid receptor agonists was optimized for drug-like properties such as cytochrome P450 inhibition, metabolic stability, aqueous solubility, and hERG ion channel inhibition. This effort culminated in the identification of the clinical candidate compound (R)-39.

  DOI：

  10.1021/ml500387y
• 作为产物：
  描述：

  1,1,1-三氟-4-甲基-3-戊烯-2-酮 、 间溴氟苯 在 magnesium 、 copper(l) iodide 作用下， 以 四氢呋喃 为溶剂， 反应 20.0h， 生成 1,1,1-trifluoro-4-methyl-4-(3-fluorophenyl)pentan-2-one
  参考文献：
  名称：

  Optimization of Drug-Like Properties of Nonsteroidal Glucocorticoid Mimetics and Identification of a Clinical Candidate

  摘要：

  A series of nonsteroidal dissociated glucocorticoid receptor agonists was optimized for drug-like properties such as cytochrome P450 inhibition, metabolic stability, aqueous solubility, and hERG ion channel inhibition. This effort culminated in the identification of the clinical candidate compound (R)-39.

  DOI：

  10.1021/ml500387y

文献信息

• Nonsteroidal Dissociated Glucocorticoid Agonists Containing Azaindoles as Steroid A-Ring Mimetics
  作者：Doris Riether、Christian Harcken、Hossein Razavi、Daniel Kuzmich、Thomas Gilmore、Jörg Bentzien、Edward J. Pack、Donald Souza、Richard M. Nelson、Alison Kukulka、Tazmeen N. Fadra、Ljiljana Zuvela-Jelaska、Josephine Pelletier、Roger Dinallo、Mark Panzenbeck、Carol Torcellini、Gerald H. Nabozny、David S. Thomson

  DOI：10.1021/jm100751q

  日期：2010.9.23

  Syntheses and structure activity relationships (SA R) of nonsteroidal glucocorticoid receptor (GR) agonists are described. These compounds contain azaindole moieties as A-ring mimetics and display various degrees of in vitro dissociation between gene transrepression and transactivation. Collagen induced arthritis studies in mouse have demonstrated that in vitro dissociated compounds (R)-16 and (R)-37 have steroid-like anti-inflammatory properties with improved metabolic side effect profiles, such as a reduced increase in body fat and scrum insulin levels, compared to steroids.
• Optimization of Drug-Like Properties of Nonsteroidal Glucocorticoid Mimetics and Identification of a Clinical Candidate
  作者：Christian Harcken、Doris Riether、Pingrong Liu、Hossein Razavi、Usha Patel、Thomas Lee、Todd Bosanac、Yancey Ward、Mark Ralph、Zhidong Chen、Donald Souza、Richard M. Nelson、Alison Kukulka、Tazmeen N. Fadra-Khan、Ljiljana Zuvela-Jelaska、Mita Patel、David S. Thomson、Gerald H. Nabozny

  DOI：10.1021/ml500387y

  日期：2014.12.11

  A series of nonsteroidal dissociated glucocorticoid receptor agonists was optimized for drug-like properties such as cytochrome P450 inhibition, metabolic stability, aqueous solubility, and hERG ion channel inhibition. This effort culminated in the identification of the clinical candidate compound (R)-39.