1-(3,4-dichlorophenyl)cycloheptanecarbonitrile | 944352-54-9

• 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: 1-(3,4-dichlorophenyl)cycloheptanecarbonitrile
• 英文别名: 1-(3,4-dichlorophenyl)cycloheptane-1-carbonitrile
• CAS: 944352-54-9
• 化学式: C₁₄H₁₅Cl₂N
• mdl: MFCD11212944
• 分子量: 268.186
• InChiKey: YOHSVZYBBYVJJL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.3
• 重原子数：
  17
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  23.8
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  1-(3,4-dichlorophenyl)cycloheptanecarbonitrile 在 sodium hydroxide 作用下， 以 1,3-丙二醇 为溶剂， 生成 1-(3,4-Dichlorophenyl)cycloheptane-1-carboxylic acid
  参考文献：
  名称：

  Discovery of N-methyl-1-(1-phenylcyclohexyl)methanamine, a novel triple serotonin, norepinephrine, and dopamine reuptake inhibitor

  摘要：

  The current work discloses a novel cyclohexylarylamine chemotype with potent inhibition of the serotonin, norepinephrine, and dopamine transporters and potential for treatment of major depressive disorder. Optimized compounds 1 (SERT, NET, DAT, IC50 = 169, 85, 21 nM) and 42 (SERT, NET, DAT IC50 = 34, 295, 90 nM) were highly brain penetrant, active in vivo in the mouse tail suspension test at 30 mpk po and were not general motor stimulants. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.01.016
• 作为产物：
  描述：

  1,6-二溴己烷 、 3,4-二氯苯乙腈 在 sodium hydride 作用下， 以 四氢呋喃 、 二甲基亚砜 为溶剂， 生成 1-(3,4-dichlorophenyl)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

• Discovery of N-methyl-1-(1-phenylcyclohexyl)methanamine, a novel triple serotonin, norepinephrine, and dopamine reuptake inhibitor
  作者：Liming Shao、Michael C. Hewitt、Fengjiang Wang、Scott C. Malcolm、Jianguo Ma、John E. Campbell、Una C. Campbell、Sharon R. Engel、Nancy A. Spicer、Larry W. Hardy、Rudy Schreiber、Kerry L. Spear、Mark A. Varney

  DOI：10.1016/j.bmcl.2011.01.016

  日期：2011.3

  The current work discloses a novel cyclohexylarylamine chemotype with potent inhibition of the serotonin, norepinephrine, and dopamine transporters and potential for treatment of major depressive disorder. Optimized compounds 1 (SERT, NET, DAT, IC50 = 169, 85, 21 nM) and 42 (SERT, NET, DAT IC50 = 34, 295, 90 nM) were highly brain penetrant, active in vivo in the mouse tail suspension test at 30 mpk po and were not general motor stimulants. (C) 2011 Elsevier Ltd. All rights reserved.
• Discovery of the First‐in‐Class Inhibitors of Hypoxia Up‐Regulated Protein 1 (HYOU1) Suppressing Pathogenic Fibroblast Activation
  作者：Dimitra Papadopoulou、Vasiliki Mavrikaki、Filippos Charalampous、Christos Tzaferis、Martina Samiotaki、Konstantinos D. Papavasileiou、Antreas Afantitis、Niki Karagianni、Maria C. Denis、Julie Sanchez、J. Robert Lane、Zacharias Faidon Brotzakis、Georgios Skretas、Dimitris Georgiadis、Alexios N. Matralis、George Kollias

  DOI：10.1002/anie.202319157

  日期：2024.4.2

  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.