3-bromo-2-isothiocyantopyridine | 1206640-75-6

• 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: 3-bromo-2-isothiocyantopyridine
• 英文别名: 3-bromo-3-aminopyridine；3-bromo-2-isothiocyanato-pyridine；3-Bromopyridin-2-isothiocyanate；3-bromo-2-isothiocyanatopyridine
• CAS: 1206640-75-6
• 化学式: C₆H₃BrN₂S
• 分子量: 215.073
• InChiKey: YHDCGHCRRTXBLS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  10
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  57.3
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3-bromo-2-isothiocyantopyridine 、 1-甲基-1-苯肼 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 3.0h， 以88%的产率得到4-(3-bromopyridin-2-yl)-1-methyl-1-phenylthiosemicarbazide
  参考文献：
  名称：

  Design, synthesis, and computational validation of novel compounds selectively targeting HER2-expressing breast cancer

  摘要：

  Human epidermal growth factor receptor (HER) is a family of multidomain proteins that plays important role in the regulation of several biological functions. HER2 is a member of HER that is highly presented in breast cancer cells. Here, we designed and synthesized a series of diaryl urea/thiourea compounds. The compounds were tested on HER2+ breast cancer cells including MCF-7 and SkBr3, compared to HER2- breast cancer cells including MDA-MB-231 and BT-549. Only compounds 12-14 at 10 µM showed selective anti-proliferative activity against MCF-7 and SkBr3 by 65-79%. Compounds 12-14 showed >80% inhibition of the intracellular kinase domain of HER2. The results obtained indicated that compounds 12-14 are selectively targeting HER2+ cells. The IC50 of compound 13 against MCF-7 and SkBR3 were 1.3 ± 0.009 and 0.73 ± 0.03 µM, respectively. Molecular docking and MD simulations (50 ns) were carried out, and their binding free energies were calculated. Compounds 12-14 formed strong hydrogen bond and pi-pi stacking interactions with the key residues Thr862 and Phe864. 3DQSAR model confirmed the role of 3-bromo substituent of pyridine ring and 4-chloro substituent of phenyl ring in the activity of the compounds. In conclusion, novel compounds, particularly 13 were developed selectively against HER2-expressing/overexpressing breast cancer cells including MCF7 and SkBr3.

  DOI：

  10.1016/j.bmcl.2020.127658
• 作为产物：
  描述：

  2-氨基-3-溴吡啶 、 硫光气 以 二氯甲烷 为溶剂， 反应 1.0h， 生成 3-bromo-2-isothiocyantopyridine
  参考文献：
  名称：

  [EN] [1, 2, 4] TRIAZOLO [1, 5-A] PYRIDINES AS JAK INHIBITORS
  [FR] [1, 2, 4]TRIAZOLO[1, 5-A]PYRIDINES UTILISÉES COMME INHIBITEURS DE JAK

  摘要：

  揭示了一种具有以下式表示的化学式的新型[1,2,4]三唑并[1,5-a]吡啶化合物（I）。这些化合物可以制备为药物组合物，并可用于预防和治疗包括人类在内的哺乳动物的各种疾病，例如关节疾病、炎症等。

  公开号：

  WO2010010184A1

文献信息

• [EN] [1, 2, 4] TRIAZOLO [1, 5-A] PYRIDINES AS JAK INHIBITORS<br/>[FR] [1, 2, 4]TRIAZOLO[1, 5-A]PYRIDINES UTILISÉES COMME INHIBITEURS DE JAK
  申请人：GALAPAGOS NV

  公开号：WO2010010184A1

  公开（公告）日：2010-01-28

  Novel [1,2,4]triazolo[1,5-a]pyridine compounds are disclosed that have a Formula represented by the following: (I). The compounds may be prepared as pharmaceutical compositions, and may be used for the prevention and treatment of a variety of conditions in mammals including humans, including by way of non-limiting example, joint disease, inflammation, and others.

  揭示了一种具有以下式表示的化学式的新型[1,2,4]三唑并[1,5-a]吡啶化合物（I）。这些化合物可以制备为药物组合物，并可用于预防和治疗包括人类在内的哺乳动物的各种疾病，例如关节疾病、炎症等。
• Computer-aided identification of novel anticancer compounds with a possible dual HER1/HER2 inhibition mechanism
  作者：Samia A. Elseginy、Glorianne Lazaro、Galal A.M. Nawwar、Kamilia M. Amin、Stephen Hiscox、Andrea Brancale

  DOI：10.1016/j.bmcl.2014.12.095

  日期：2015.2

  HER1 and HER2 are frequently overexpressed in human tumors where they drive cellular proliferation. For this reason they are considered important targets in anticancer therapy with dual HER1/HER2 inhibitors being recently approved and marketed. In this paper we report the identification of a series of compounds with anticancer activity by a combined virtual screening approach on the kinase domains of HER1 and HER2. 6 hit compounds that present a sub- or low-micromolar activity in two cell-based assays, were initially identified and a subsequent design cycle led to the synthesis of a compound with nanomolar activity in the cell-based assays. (C) 2015 Elsevier Ltd. All rights reserved.
• Design, synthesis, and computational validation of novel compounds selectively targeting HER2-expressing breast cancer
  作者：Samia A. Elseginy、Rania Hamdy、Varsha Menon、Ahmed M. Almehdi、Raafat El-Awady、Sameh S.M. Soliman

  DOI：10.1016/j.bmcl.2020.127658

  日期：2020.12

  Human epidermal growth factor receptor (HER) is a family of multidomain proteins that plays important role in the regulation of several biological functions. HER2 is a member of HER that is highly presented in breast cancer cells. Here, we designed and synthesized a series of diaryl urea/thiourea compounds. The compounds were tested on HER2+ breast cancer cells including MCF-7 and SkBr3, compared to HER2- breast cancer cells including MDA-MB-231 and BT-549. Only compounds 12-14 at 10 µM showed selective anti-proliferative activity against MCF-7 and SkBr3 by 65-79%. Compounds 12-14 showed >80% inhibition of the intracellular kinase domain of HER2. The results obtained indicated that compounds 12-14 are selectively targeting HER2+ cells. The IC50 of compound 13 against MCF-7 and SkBR3 were 1.3 ± 0.009 and 0.73 ± 0.03 µM, respectively. Molecular docking and MD simulations (50 ns) were carried out, and their binding free energies were calculated. Compounds 12-14 formed strong hydrogen bond and pi-pi stacking interactions with the key residues Thr862 and Phe864. 3DQSAR model confirmed the role of 3-bromo substituent of pyridine ring and 4-chloro substituent of phenyl ring in the activity of the compounds. In conclusion, novel compounds, particularly 13 were developed selectively against HER2-expressing/overexpressing breast cancer cells including MCF7 and SkBr3.