1-(5-chloropyridin-2-yl)-1,4-diazepane

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: 1-(5-chloropyridin-2-yl)-1,4-diazepane
• 化学式: C₁₀H₁₄ClN₃
• 分子量: 211.694
• InChiKey: QROUAUKPBGCWPX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  14
• 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：
  28.2
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1-(5-chloropyridin-2-yl)-1,4-diazepane 在 盐酸 、 碳酸氢钠 、 potassium iodide 作用下， 以 乙醚 、 异丙醇 为溶剂， 反应 12.0h， 生成 4-(4-(5-chloropyridin-2-yl)-1,4-diazepan-1-yl)-1-(4-fluoro-phenyl)butan-1-one dihydrochloride
  参考文献：
  名称：

  SYA 013 analogs as moderately selective sigma-2 (σ2) ligands: Structure-affinity relationship studies

  摘要：

  Several lines of evidence suggest that selective sigma-2 (sigma(2)) ligands might be useful for the treatment of solid tumors. However, very few selective sigma(2) ligands have been identified. This study was aimed at identifying new selective sigma(2) receptor ligands using a previously identified agent, SYA 013 as a lead. Four groups, homopiperazine, piperazine, tropane and selected oxime analogs of the homopiperazines were identified, synthesized and subsequently screened at the sigma(1) and sigma(2) receptors. The results demonstrate that these scaffolds can be modified to obtain selective sigma(2) receptor ligands. 1-(5-Chloropyridin-2-yl)-4-(3-((4-fluorophenyl)thio)propyl)-1,4-diazepane, 7 and 3-(4-chlorophenyl)-8-(3-((2-fluorophenyl)thio)propyl)-8-azabicyclo[ 3.2.1]octan-3-ol, 21 were identified as the highest binding affinity ligands (sigma(2)Ki = 2.2 nM) and (4-(4-(5-chloropyridin-2-yl)-1,4-diazepan-1-yl)-1-(4-fluorophenyl)-butan-1-one oxime, 22 as a high affinity and the most selective ligand for the sigma(2) receptor (sigma(1)Ki/sigma(2)Ki = 41.8).

  DOI：

  10.1016/j.bmc.2019.01.035
• 作为产物：
  描述：

  1,4-二氮杂环庚烷-1-甲酸叔丁酯 在 盐酸 、 N,N-二异丙基乙胺 作用下， 以 1,4-二氧六环 、 N-甲基吡咯烷酮 、 水 为溶剂， 反应 2.0h， 生成 1-(5-chloropyridin-2-yl)-1,4-diazepane
  参考文献：
  名称：

  [EN] INHIBITORS OF DIHYDROCERAMIDE DESATURASE FOR TREATING DISEASE
  [FR] INHIBITEURS DE LA DIHYDROCÉRAMIDE DÉSATURASE POUR LE TRAITEMENT D'UNE MALADIE

  摘要：

  本文披露了二氢神经酰胺脱饱和酶1（Des1）抑制剂化合物和组合物，这些化合物和组合物在治疗疾病方面非常有用，例如代谢紊乱，预期通过抑制Des1对患者具有治疗作用。还提供了在人类或动物受试者中抑制Des1活性的方法。

  公开号：

  WO2019140188A1

文献信息

• New analogs of SYA013 as sigma-2 ligands with anticancer activity
  作者：Gladys Asong、Xue Y. Zhu、Barbara Bricker、Terrick Andey、Felix Amissah、Nazarius Lamango、Seth Y. Ablordeppey

  DOI：10.1016/j.bmc.2019.04.012

  日期：2019.6

  moderate selectivity for the sigma-2 receptor. Given the overexpression of sigma receptors in solid tumors and reports of sigma ligands with anticancer activities, we selected 1 for evaluation in several solid tumor cell lines. In addition, we have synthesized new analogs of 1 and now report that several of them bind preferentially at the sigma-2 receptor and have shown inhibition of several cancer cell lines

  我们先前的研究表明4-（4-（4-氯苯基）-1,4-二氮杂-1-基）-1-（4-氟苯基）丁-1--1-酮·2HCl（SYA013）1为sigma配体对sigma-2受体具有中等选择性。鉴于实体肿瘤中sigma受体的过表达以及具有抗癌活性的sigma配体的报道，我们选择1在几种实体瘤细胞系中进行评估。此外，我们合成了1的新类似物，现在报道其中一些类似物优先与sigma-2受体结合，并显示出对多种癌细胞系（包括MDA-MB-231，MDA-MB-486，A549，PC）的抑制作用-3，MIA PaCa-2和Panc-1细胞。特别地，化合物1和12已显示出对Panc-1细胞系的亚微摩尔活性。还发现这些化合物中的几种对癌细胞具有选择性毒性，
• Discovery of Potent and Selective Transient Receptor Potential Vanilloid 1 (TRPV1) Agonists with Analgesic Effects <i>In Vivo</i> Based on the Functional Conversion Induced by Altering the Orientation of the Indazole Core
  作者：Qianqian Liang、Zhen Qiao、Qiqi Zhou、Dengqi Xue、KeWei Wang、Liming Shao

  DOI：10.1021/acs.jmedchem.2c00469

  日期：2022.9.8
• INHIBITORS OF DIHYDROCERAMIDE DESATURASE FOR TREATING DISEASE
  申请人：Centaurus Therapeutics

  公开号：EP3737361A1

  公开（公告）日：2020-11-18
• Inhibitors of Dihydroceramide Desaturase For Treating Disease
  申请人：Centaurus Therapeutics

  公开号：US20200339535A1

  公开（公告）日：2020-10-29

  Disclosed herein are dihydroceramide desaturase 1 (Des1) inhibitor compounds and compositions, which are useful in the treatment of diseases, such as metabolic disorders, where inhibition of Des1 is expected to be therapeutic to a patient. Methods of inhibition of Des1 activity in a human or animal subject are also provided.