4-((2-amino-2-methylpropyl)amino)-2-(trifluoromethyl)benzonitrile

• 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: 4-((2-amino-2-methylpropyl)amino)-2-(trifluoromethyl)benzonitrile
• 英文别名: 4-(2-Amino-2-methylpropylamino)-2-trifluoromethylbenzonitrile；4-[(2-amino-2-methylpropyl)amino]-2-(trifluoromethyl)benzonitrile
• 化学式: C₁₂H₁₄F₃N₃
• 分子量: 257.258
• InChiKey: RCYDZEKDVOLYEO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  18
• 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：
  61.8
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  4-((2-amino-2-methylpropyl)amino)-2-(trifluoromethyl)benzonitrile 在 sodium hydride 、 三乙胺 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 7.17h， 生成 4-(3-(2-(difluoromethoxy)benzyl)-4,4-dimethyl-2-oxoimidazolidin-1-yl)-2-(trifluoromethyl)benzonitrile
  参考文献：
  名称：

  Electronic effect‐dependent intramolecular non‐covalent interactions on the activity of 4,4‐dimethylimidazolidin‐2‐one pharmacophore‐based androgen receptor antagonists

  摘要：

  AbstractBecause androgen receptor (AR) signalling is important for the development and progression of prostate cancer (PC), AR antagonists are utilized in clinical practices to treat PC and are referred to as androgen deprivation therapy (ADT). However, continued administration of AR antagonists often results in the development of resistance, known as castration‐resistant prostate cancer (CRPC). Despite castration, it has been demonstrated that AR signalling continues to be fundamental to tumour growth. In this regard, a series of readily synthesizable 4,4‐dimethylimidazolidine‐2‐one pharmacophore‐based AR antagonists (FAR01‐FAR11) were designed and synthesized. Androgen‐dependent LNCaP PC cell line was used to test the AR‐antagonist activity of these compounds in vitro and compared with the U.S. Food and Drug Administration (FDA) approved second‐generation enzalutamide. In our previous work, rigid thiohydantoin pharmacophore in enzalutamide is replaced by the flexible 4,4‐dimethylimidazolidin‐2‐one. In order to improve the flexibility further, one methylene group is introduced between the pharmacophore and one of the aromatic ring. Despite the fact that the amide functional group is a crucial characteristic for building AR antagonists, this class of molecules lacks one. FAR06 has the exact same activity as enzalutamide (IC50: 0.782 μM) with an IC50 value of 0.801 μM among the series of compounds.

  DOI：

  10.1111/cbdd.14151
• 作为产物：
  描述：

  1,2-二氨基-2-甲基丙烷 、 4-氟-2-(三氟甲基)苯甲腈 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 3.0h， 以72%的产率得到4-((2-amino-2-methylpropyl)amino)-2-(trifluoromethyl)benzonitrile
  参考文献：
  名称：

  [EN] NOVEL IMIDAZOLIDINE-2,4-DIONE DERIVATIVES
  [FR] NOUVEAUX DÉRIVÉS D'IMIDAZOLIDINE-2,4-DIONE

  摘要：

  本申请的主题是公式（I）的新型咪唑烷-2,4-二酮衍生物。这些产品具有抗增殖活性，特别适用于治疗与异常细胞增殖相关的病理状态和疾病，如癌症。该发明还涉及含有上述产品的药物组合物以及它们用于制备药物的用途。

  公开号：

  WO2015100617A1

文献信息

• Cyanophenyl derivative
  申请人：Yamanouchi Pharmaceutical Co. Ltd.

  公开号：US06673799B1

  公开（公告）日：2004-01-06

  This application relates to a piperazino-substituted novel cyanophenyl derivative in which a substituted carbamoyl or substituted sulfamoyl group having an aryl, heterocyclic or the like group that may have a substituent group is bonded to one nitrogen atom on the piperazine ring. The compound of this application has an anti-androgen action and is useful in preventing or treating prostatic cancer, benign prostatic hyperplasia and the like diseases.

  该申请涉及一种哌嗪取代的新型氰基苯基衍生物，其中带有芳基、杂环或类似的基团的取代羰酰基或取代磺酰基与哌嗪环上的一个氮原子结合。该申请的化合物具有抗雄激素作用，并可用于预防或治疗前列腺癌、良性前列腺增生等疾病。
• [EN] NOVEL IMIDAZOLIDINE-2,4-DIONE DERIVATIVES<br/>[FR] NOUVEAUX DÉRIVÉS D'IMIDAZOLIDINE-2,4-DIONE
  申请人：BEAUFOUR IPSEN TIANJIN PHARMACEUTICAL CO LTD

  公开号：WO2015100617A1

  公开（公告）日：2015-07-09

  A subject of the present application is novel imidazolidine-2,4-dione derivatives of formula (I). These products have an anti-proliferative activity. They are particularly useful for treating the pathological states and the diseases linked to an abnormal cell proliferation such as cancers. The invention also relates to the pharmaceutical compositions containing said products and their use for the preparation of a medicament.

  本申请的主题是公式（I）的新型咪唑烷-2,4-二酮衍生物。这些产品具有抗增殖活性，特别适用于治疗与异常细胞增殖相关的病理状态和疾病，如癌症。该发明还涉及含有上述产品的药物组合物以及它们用于制备药物的用途。
• CYANOPHENYL DERIVATIVES
  申请人：Astellas Pharma Inc.

  公开号：EP1122242B1

  公开（公告）日：2008-01-16
• NOVEL IMIDAZOLIDINE-2,4-DIONE DERIVATIVES
  申请人：IPSEN PHARMA S.A.S.

  公开号：EP3089974A1

  公开（公告）日：2016-11-09
• US6673799B1
  申请人：——

  公开号：US6673799B1

  公开（公告）日：2004-01-06