6-(3-methanesulfonyl-phenyl)-6-methyl-4-trifluoromethylhept-1-yn-4-ol | 1562399-33-0

• 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: 6-(3-methanesulfonyl-phenyl)-6-methyl-4-trifluoromethylhept-1-yn-4-ol
• CAS: 1562399-33-0
• 化学式: C₁₆H₁₉F₃O₃S
• 分子量: 348.386
• InChiKey: VMYFYFSAJHWHBD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.07
• 重原子数：
  23.0
• 可旋转键数：
  5.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  54.37
• 氢给体数：
  1.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  6-(3-methanesulfonyl-phenyl)-6-methyl-4-trifluoromethylhept-1-yn-4-ol 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-methyl-4-(3-methylsulfonylphenyl)-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 在 ruthenium trichloride 、 sodium periodate 、 magnesium 、 氢化铝 、 mercury dichloride 作用下， 以 四氢呋喃 、 水 、 乙腈 为溶剂， 反应 23.5h， 生成 6-(3-methanesulfonyl-phenyl)-6-methyl-4-trifluoromethylhept-1-yn-4-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

文献信息

• Identification of Highly Efficacious Glucocorticoid Receptor Agonists with a Potential for Reduced Clinical Bone Side Effects
  作者：Christian Harcken、Doris Riether、Daniel Kuzmich、Pingrong Liu、Raj Betageri、Mark Ralph、Michel Emmanuel、Jonathan T. Reeves、Angela Berry、Donald Souza、Richard M. Nelson、Alison Kukulka、Tazmeen N. Fadra、Ljiljana Zuvela-Jelaska、Roger Dinallo、Jörg Bentzien、Gerald H. Nabozny、David S. Thomson

  DOI：10.1021/jm4019178

  日期：2014.2.27

  Synthesis and structure-activity relationship (SAR) of a series of nonsteroidal glucocorticoid receptor (GR) agonists are described. These compounds contain "diazaindole" moieties and display different transcriptional regulatory profiles in vitro and are considered "dissociated" between gene transrepression and transactivation. The lead optimization effort described in this article focused in particular on limiting the transactivation of genes which result in bone side effects and these were assessed in vitro in MG-63 osteosarcoma cells, leading to the identification of (R)-18 and (R)-21. These compounds maintained anti-inflammatory activity in vivo in collagen induced arthritis studies in mouse but had reduced effects on bone relevant parameters compared to the widely used synthetic glucocorticoid prednisolone 2 in vivo. To our knowledge, we are the first to report on selective glucocorticoid ligands with reduced bone loss in a preclinical in vivo model.