1-(pyridin-3-yl)cycloheptanecarbonitrile | 1510908-26-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: 1-(pyridin-3-yl)cycloheptanecarbonitrile
• 英文别名: 1-Pyridin-3-ylcycloheptane-1-carbonitrile
• CAS: 1510908-26-5
• 化学式: C₁₃H₁₆N₂
• 分子量: 200.283
• InChiKey: DEUZLSVHLKUJDF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  15
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  36.7
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  1-(pyridin-3-yl)cycloheptanecarbonitrile 以 四氢呋喃 为溶剂， 以20 %的产率得到(1-(pyridin-3-yl)cycloheptyl)methanamine
  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：

  1,6-二溴己烷 、 3-吡啶乙腈 在 sodium hydride 作用下， 以 四氢呋喃 、 二甲基亚砜 为溶剂， 以19 %的产率得到1-(pyridin-3-yl)cycloheptanecarbonitrile
  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

文献信息

• [EN] INDOLE CARBOXAMIDE DERIVATIVES AS P2X7 RECEPTOR ANTAGONISTS<br/>[FR] DÉRIVÉS D'INDOLE CARBOXAMIDE UTILISÉS EN TANT QU'ANTAGONISTES DU RÉCEPTEUR P2X7
  申请人：ACTELION PHARMACEUTICALS LTD

  公开号：WO2014097140A1

  公开（公告）日：2014-06-26

  The invention relates to indole carboxamide derivatives of formula (I), wherein R1, R2, R3, R4, R5, R6, R7, R8, R9, R10 and n are as defined in the description, their preparation and their use as pharmaceutically active compounds.

  这项发明涉及式(I)的吲哚羧酰胺衍生物，其中R1、R2、R3、R4、R5、R6、R7、R8、R9、R10和n如描述中所定义，它们的制备以及它们作为药用活性化合物的用途。
• INDOLE CARBOXAMIDE DERIVATIVES AS P2X7 RECEPTOR ANTAGONISTS
  申请人：ACTELION PHARMACEUTICALS LTD

  公开号：US20150344425A1

  公开（公告）日：2015-12-03

  The invention relates to indole carboxamide derivatives of formula (I), wherein R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 and n are as defined in the description, their preparation and their use as pharmaceutically active compounds.

  该发明涉及式(I)的吲哚羧酰胺衍生物，其中R1、R2、R3、R4、R5、R6、R7、R8、R9、R10和n如描述中所定义，它们的制备以及它们作为药物活性化合物的用途。
• US9556117B2
  申请人：——

  公开号：US9556117B2

  公开（公告）日：2017-01-31