1-((4-chlorophenyl)amino)cycloheptanecarbonitrile | 93568-78-6

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: 1-((4-chlorophenyl)amino)cycloheptanecarbonitrile
• 英文别名: 1-((4-chlorophenyl)amino)cycloheptane-1-carbonitrile；1-<4-Chlor-anilino>-1-cyan-cycloheptan；1-(4-Chloroanilino)cycloheptane-1-carbonitrile
• CAS: 93568-78-6
• 化学式: C₁₄H₁₇ClN₂
• mdl: MFCD12846743
• 分子量: 248.755
• InChiKey: NALDUXVMXUXMCV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  17
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  35.8
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  1-((4-chlorophenyl)amino)cycloheptanecarbonitrile 在 lithium aluminium tetrahydride 作用下， 以 乙醚 为溶剂， 生成 1-(aminomethyl)-N-(4-chlorophenyl)cycloheptanamine
  参考文献：
  名称：

  Discovery of the First‐in‐Class Inhibitors of Hypoxia Up‐Regulated Protein 1 (HYOU1) Suppressing Pathogenic Fibroblast Activation

  摘要：

  Fibroblasts are key regulators of inflammation, fibrosis, and cancer. Targeting their activation in these complex diseases has emerged as a novel strategy to restore tissue homeostasis. Here, we present a multidisciplinary lead discovery approach to identify and optimize small molecule inhibitors of pathogenic fibroblast activation. The study encompasses medicinal chemistry, molecular phenotyping assays, chemoproteomics, bulk RNA‐sequencing analysis, target validation experiments, and chemical absorption, distribution, metabolism, excretion and toxicity (ADMET)/pharmacokinetic (PK)/in vivo evaluation. The parallel synthesis employed for the production of the new benzamide derivatives enabled us to a) pinpoint key structural elements of the scaffold that provide potent fibroblast‐deactivating effects in cells, b) discriminate atoms or groups that favor or disfavor a desirable ADMET profile, and c) identify metabolic “hot spots”. Furthermore, we report the discovery of the first‐in‐class inhibitor leads for hypoxia up‐regulated protein 1 (HYOU1), a member of the heat shock protein 70 (HSP70) family often associated with cellular stress responses, particularly under hypoxic conditions. Targeting HYOU1 may therefore represent a potentially novel strategy to modulate fibroblast activation and treat chronic inflammatory and fibrotic disorders.

  DOI：

  10.1002/anie.202319157
• 作为产物：
  描述：

  三甲基氰硅烷 、 对氯苯胺 、 环庚酮 反应 0.5h， 生成 1-((4-chlorophenyl)amino)cycloheptanecarbonitrile
  参考文献：
  名称：

  [EN] ANTI-INFLAMMATORY CARBOXAMIDE DERIVATIVES
  [FR] DÉRIVÉS DE CARBOXAMIDE ANTI-INFLAMMATOIRES

  摘要：

  本发明提供了化合物(I)的配方或其药学上可接受的盐、水合物或异构体。本发明还提供了包含配方(I)的药物组合物，以及它们在治疗中的使用，特别是在治疗炎症状况方面的使用。本发明的化合物具有广泛和强大的抗炎作用，并具有治疗安全性的优点。

  公开号：

  WO2022189636A1