2-[(2R)-2-hydroxy-4-methyl-4-(5-methylsulfonyl-2,3-dihydro-1-benzofuran-7-yl)-2-(trifluoromethyl)pentyl]-1H-indole-6-carbonitrile | 1350438-11-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: 2-[(2R)-2-hydroxy-4-methyl-4-(5-methylsulfonyl-2,3-dihydro-1-benzofuran-7-yl)-2-(trifluoromethyl)pentyl]-1H-indole-6-carbonitrile
• CAS: 1350438-11-7
• 化学式: C₂₅H₂₅F₃N₂O₄S
• 分子量: 506.546
• InChiKey: QTOKABCAHAKYAS-DEOSSOPVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  35
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  112
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  5-bromo-7-[2-(2,2-dimethyl-4-trifluoromethyl-[1,3] dioxolan-4-yl)-1,1-dimethylethyl]-2,3-dihydrobenzofuran 在 盐酸 、 ruthenium trichloride 、 sodium periodate 、 copper(l) iodide 、 正丁基锂 、 二氯双(三邻甲苯膦)合钯(II) 、 caesium carbonate 、 三乙胺 、 氢化铝 、 mercury dichloride 作用下， 以 四氢呋喃 、 甲醇 、 正己烷 、 二甲基亚砜 、 异丙醇 、 乙腈 为溶剂， 反应 12.0h， 生成 2-[(2S)-2-hydroxy-4-methyl-4-(5-methylsulfonyl-2,3-dihydro-1-benzofuran-7-yl)-2-(trifluoromethyl)pentyl]-1H-indole-6-carbonitrile 、 2-[(2R)-2-hydroxy-4-methyl-4-(5-methylsulfonyl-2,3-dihydro-1-benzofuran-7-yl)-2-(trifluoromethyl)pentyl]-1H-indole-6-carbonitrile
  参考文献：
  名称：

  Non-steroidal dissociated glucocorticoid agonists: indoles as A-ring mimetics and function-regulating pharmacophores

  摘要：

  We report a SAR of non-steroidal glucocorticoid mimetics that utilize indoles as A-ring mimetics. Detailed SAR is discussed with a focus on improving PR and MR selectivity, GR agonism, and in vitro dissociation profile. SAR analysis led to compound (R)-33 which showed high PR and MR selectivity, potent agonist activity, and reduced transactivation activity in the MMTV and aromatase assays. The compound is equipotent to prednisolone in the LPS-TNF model of inflammation. In mouse CIA, at 30 mg/kg compound (R)-33 inhibited disease progression with an efficacy similar to the 3 mg/kg dose of prednisolone. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.09.018

文献信息

• Non-steroidal dissociated glucocorticoid agonists: indoles as A-ring mimetics and function-regulating pharmacophores
  作者：Raj Betageri、Thomas Gilmore、Daniel Kuzmich、Thomas M. Kirrane、Jörg Bentzien、Dieter Wiedenmayer、Younes Bekkali、John Regan、Angela Berry、Bachir Latli、Alison J. Kukulka、Tazmeen N. Fadra、Richard M. Nelson、Susan Goldrick、Ljiljana Zuvela-Jelaska、Don Souza、Josephine Pelletier、Roger Dinallo、Mark Panzenbeck、Carol Torcellini、Heewon Lee、Edward Pack、Christian Harcken、Gerald Nabozny、David S. Thomson

  DOI：10.1016/j.bmcl.2011.09.018

  日期：2011.11

  We report a SAR of non-steroidal glucocorticoid mimetics that utilize indoles as A-ring mimetics. Detailed SAR is discussed with a focus on improving PR and MR selectivity, GR agonism, and in vitro dissociation profile. SAR analysis led to compound (R)-33 which showed high PR and MR selectivity, potent agonist activity, and reduced transactivation activity in the MMTV and aromatase assays. The compound is equipotent to prednisolone in the LPS-TNF model of inflammation. In mouse CIA, at 30 mg/kg compound (R)-33 inhibited disease progression with an efficacy similar to the 3 mg/kg dose of prednisolone. (C) 2011 Elsevier Ltd. All rights reserved.