3-bromo-5-trifluoromethylphenylisocyanate | 307990-40-5

• 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: 3-bromo-5-trifluoromethylphenylisocyanate
• 英文别名: 1-bromo-3-isocyanato-5-(trifluoromethyl)benzene
• CAS: 307990-40-5
• 化学式: C₈H₃BrF₃NO
• 分子量: 266.017
• InChiKey: PGOJVIXXAXKMAS-UHFFFAOYSA-N

物化性质

• 沸点：
  221.6±40.0 °C(Predicted)
• 密度：
  1?+-.0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  14
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  29.4
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  3-bromo-5-trifluoromethylphenylisocyanate 在 四(三苯基膦)钯 作用下， 以 1,4-二氧六环 、 二氯甲烷 、 水 为溶剂， 反应 0.33h， 生成 2-(dimethylamino)ethyl 4-methoxy-3-(3-(3-(pyridin-3-yl)-5-(trifluoromethyl)phenyl)ureido)benzoate
  参考文献：
  名称：

  Discovery of novel VEGFR-2 inhibitors. Part 5: Exploration of diverse hinge-binding fragments via core-refining approach

  摘要：

  Pathological angiogenesis plays a critical role in numerous diseases including malignancy. VEGFR-2 is the central regulators in angiogenesis and has become a promising target for anticancer drug design. We have identified a novel biphenyl-aryl urea incorporated with salicyladoxime (BPS-7) as potent VEGFR-2 inhibitor. As a continuation to our previous research, various aromatic-heterocyclic were introduced as hinge-binding fragment via a core-refining approach. Interestingly, many compounds exhibited comparable VEGFR-2 inhibition to Sorafenib. In particular, 12e and 12o displayed excellent VEGFR-2 inhibitory activity with IC50 values of 0.50 nM and 0.79 nM, respectively. Several title compounds showed considerable antiproliferative activity against A549 and SMMC-7721 cells. In addition, molecular docking was performed to rationalize the efficiency of the better compounds. These results will be instructive for further inhibitor design and optimization. (C) 2015 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2015.08.045
• 作为产物：
  描述：

  3-氨基-5-溴三氟甲苯 、 氯甲酸三氯甲酯 在 盐酸 作用下， 以 乙醚 、 甲苯 为溶剂， 生成 3-bromo-5-trifluoromethylphenylisocyanate
  参考文献：
  名称：

  Glucagon antagonists/inverse agonists

  摘要：

  揭示了一类新的化合物，其化学式为（I），其中V、A、Y、Z、R1、E、X和D的定义如规范中所述。这些化合物作用于拮抗胰高血糖素激素对胰高血糖素受体的作用。由于这些化合物对胰高血糖素受体的拮抗作用，它们适用于治疗或预防由胰高血糖素介导的疾病和病症，如高血糖、1型糖尿病、2型糖尿病和肥胖症。

  公开号：

  US06503949B1

文献信息

• Glucagon Antagonists/Inverse Agonists
  申请人：Lau Jesper

  公开号：US20090143592A1

  公开（公告）日：2009-06-04

  A novel class of compounds, which act to antagonize the action of the glucagon hormone on the glucagon receptor. Owing to their antagonizing effect of the glucagon receptor the compounds may be suitable for the treatment and/or prevention of any glucagon-mediated conditions and diseases such as hyperglycemia, Type 1 diabetes, Type 2 diabetes and obesity.

  一种新型化合物，可拮抗胰高血糖素对胰高血糖素受体的作用。由于这些化合物对胰高血糖素受体的拮抗作用，这些化合物可能适用于治疗和/或预防任何胰高血糖素介导的疾病和病症，如高血糖、1型糖尿病、2型糖尿病和肥胖症。
• Novel Glucagon Receptor Antagonists with Improved Selectivity over the Glucose-Dependent Insulinotropic Polypeptide Receptor
  作者：János T. Kodra、Anker Steen Jørgensen、Birgitte Andersen、Carsten Behrens、Christian Lehn Brand、Inger Thøger Christensen、Mette Guldbrandt、Claus Bekker Jeppesen、Lotte B. Knudsen、Peter Madsen、Erica Nishimura、Christian Sams、Ulla G. Sidelmann、Raymon A. Pedersen、Francis C. Lynn、Jesper Lau

  DOI：10.1021/jm7015599

  日期：2008.9.11

  Optimization of a new series of small molecule human glucagon receptor (hGluR) antagonists is described. In the process of optimizing glucagon receptor antagonists, we counter-screened against the closeli related human gastric inhibitory polypeptide receptor (hGIPR), and through structure activity analysis, we obtained compounds with low nanomolar affinities toward the hGluR, which were selective against the hGIPR and the human glucagon-like peptide-1 receptor (hGLP-1R). In the best cases, we obtained a >50 fold selectivity for the hGluR over the hGIPR and a > 1000 fold selectivity over the hGLP-1R. A potent and selective glucagon receptor antagonist was demonstrated to inhibit glucagon-induced glycogenolysis in primary rat hepatocytes as well as to lower glucagon-induced hyperolycemia in Sprague-Dawley rats. Furthermore. the compound was shown to lower blood glucose in the ob/ob mouse after oral dosing.
• GLUCAGON ANTAGONISTS/INVERSE AGONISTS
  申请人：NOVO NORDISK A/S

  公开号：EP1183229B1

  公开（公告）日：2005-10-26
• US6503949B1
  申请人：——

  公开号：US6503949B1

  公开（公告）日：2003-01-07
• US6875760B2
  申请人：——

  公开号：US6875760B2

  公开（公告）日：2005-04-05