4-(2-oxo-3-(p-tolyl)-2,3-dihydro-1H-benzo[d]imidazol-1-yl)-2-(trifluoromethyl)benzonitrile | 1363401-32-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并咪唑类
• 英文名称: 4-(2-oxo-3-(p-tolyl)-2,3-dihydro-1H-benzo[d]imidazol-1-yl)-2-(trifluoromethyl)benzonitrile
• 英文别名: 4-[3-(4-Methylphenyl)-2-oxobenzimidazol-1-yl]-2-(trifluoromethyl)benzonitrile
• CAS: 1363401-32-4
• 化学式: C₂₂H₁₄F₃N₃O
• 分子量: 393.368
• InChiKey: QGXSENHENIHRFJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5
• 重原子数：
  29
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  47.3
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  4-氟-2-(三氟甲基)苯甲腈 在 copper diacetate 、 potassium carbonate 、 三乙胺 作用下， 以 二氯甲烷 、 二甲基亚砜 为溶剂， 反应 216.0h， 生成 4-(2-oxo-3-(p-tolyl)-2,3-dihydro-1H-benzo[d]imidazol-1-yl)-2-(trifluoromethyl)benzonitrile
  参考文献：
  名称：

  Design of oxobenzimidazoles and oxindoles as novel androgen receptor antagonists

  摘要：

  Oxobenzimidazoles (e.g., 1), a novel series of androgen receptor (AR) antagonists, were discovered through de novo design guided by structure-based drug design. The compounds in this series were reasonably permeable and metabolically stable, but suffered from poor solubility. The incorporation of three dimensional structural features led to improved solubility. In addition, the observation of a 'flipped' binding mode of an oxobenzimidazole analog in an AR ligand binding domain (LBD) model, led to the design and discovery of the novel oxindole series (e.g., 2) that is a potent full antagonist of AR.[GRAPHICS]. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.01.116

文献信息

• COMPOUNDS AND METHODS FOR THE TARGETED DEGRADATION OF ANDROGEN RECEPTOR AND ASSOCIATED METHODS OF USE
  申请人：Arvinas Operations, Inc.

  公开号：US20220144809A1

  公开（公告）日：2022-05-12

  Bifunctional compounds, which find utility as modulators of androgen receptor (AR), are described herein. In particular, the bifunctional compounds of the present disclosure contain on one end a moiety that binds to the cereblon E3 ubiquitin ligase and on the other end a moiety which binds AR, such that the target protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of target protein. The bifunctional compounds of the present disclosure exhibit a broad range of pharmacological activities associated with degradation/inhibition of target protein. Diseases or disorders that result from aberrant regulation of the target protein are treated or prevented with compounds and compositions of the present disclosure.

  本文描述了具有雄激素受体（AR）调节剂作用的双功能化合物。特别地，本公开的双功能化合物在一端含有结合到cereblon E3泛素连接酶的基团，在另一端含有结合到AR的基团，使得靶蛋白质位于泛素连接酶附近以促进靶蛋白质的降解（和抑制）。本公开的双功能化合物表现出与靶蛋白质的降解/抑制相关的广泛的药理活性。使用本公开的化合物和组合物治疗或预防由靶蛋白质异常调节引起的疾病或障碍。
• Design of oxobenzimidazoles and oxindoles as novel androgen receptor antagonists
  作者：Chuangxing Guo、Mason Pairish、Angelica Linton、Susan Kephart、Martha Ornelas、Asako Nagata、Benjamin Burke、Liming Dong、Jon Engebretsen、Andrea N. Fanjul

  DOI：10.1016/j.bmcl.2012.01.116

  日期：2012.4

  Oxobenzimidazoles (e.g., 1), a novel series of androgen receptor (AR) antagonists, were discovered through de novo design guided by structure-based drug design. The compounds in this series were reasonably permeable and metabolically stable, but suffered from poor solubility. The incorporation of three dimensional structural features led to improved solubility. In addition, the observation of a 'flipped' binding mode of an oxobenzimidazole analog in an AR ligand binding domain (LBD) model, led to the design and discovery of the novel oxindole series (e.g., 2) that is a potent full antagonist of AR.[GRAPHICS]. (C) 2012 Elsevier Ltd. All rights reserved.