methyl 5-bromo-2-[methyl(methylsulfonyl)amino]benzoate | 654682-76-5

• 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: methyl 5-bromo-2-[methyl(methylsulfonyl)amino]benzoate
• 英文别名: Methyl 5-bromo-2-[methyl(methylsulfonyl)amino]benzoate
• CAS: 654682-76-5
• 化学式: C₁₀H₁₂BrNO₄S
• 分子量: 322.18
• InChiKey: ZIRLLDHQJSWAED-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  17
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  72.1
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  methyl 5-bromo-2-[methyl(methylsulfonyl)amino]benzoate 在 sodium hydride 作用下， 以 四氢呋喃 为溶剂， 反应 4.0h， 生成 8-Bromo-1,5-dimethylpyrazolo[4,3-c][2,1]benzothiazine 4,4-dioxide
  参考文献：
  名称：

  Structure-based discovery of cellular-active allosteric inhibitors of FAK

  摘要：

  In order to develop potent and selective focal adhesion kinase (FAK) inhibitors, synthetic studies on pyrazolo[ 4,3-c][2,1]benzothiazines targeted for the FAK allosteric site were carried out. Based on the X-ray structural analysis of the co-crystal of the lead compound, 8-(4-ethylphenyl)-5-methyl-1,5-dihydropyrazolo[4,3-c][2,1]benzothiazine 4,4-dioxide 1 with FAK, we designed and prepared 1,5-dimethyl-1,5-dihydropyrazolo[4,3-c][2,1]benzothiazin derivatives which selectively inhibited kinase activity of FAK without affecting seven other kinases. The optimized compound, N-(4-tert-butylbenzyl)-1,5-dimethyl-1,5-dihydropyrazolo[4,3-c][2,1]benzothiazin-8-amine 4,4-dioxide 30 possessed significant FAK kinase inhibitory activities both in cell-free (IC50 = 0.64 mu M) and in cellular assays (IC50 = 7.1 mu M). These results clearly demonstrated a potential of FAK allosteric inhibitors as antitumor agents. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.01.047
• 作为产物：
  描述：

  5-溴氨基苯甲酸甲酯 在 sodium hydride 、 三乙胺 作用下， 以 正己烷 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 4.25h， 生成 methyl 5-bromo-2-[methyl(methylsulfonyl)amino]benzoate
  参考文献：
  名称：

  Synthesis, Characterization and Biological Activities of 2-[(Methyl sulfonyl)]amino Benzoic Acid Derivatives and Their Metal Complexes

  摘要：

  磺酰胺衍生物及其金属复合物是公认的药物分子，因为这个基团在大多数药物结构中都扮演着重要的功能性角色，具有恒定性和人体耐受性。磺酰胺类化合物具有巨大的生物潜力，如抗菌、释放胰岛素、抑制碳酸酐酶、抗炎、抗真菌和抗肿瘤等活性。在本研究中，2-[（甲基磺酰基）]氨基苯甲酸使用甲基等烷基化剂进行 N-烷基化。由于存在-COOH、-SO2、N-等电子捐赠基团，上述分子可作为一种极好的螯合剂。这些取代的 N-烷基磺酰胺配体与一些内外过渡金属（如 Co(II)、Cu(II)、Ce(II)、Pr(II)、Dy(II) 和 Nd(II)）进行处理，形成配位配合物。这些新合成的磺酰胺类化合物及其金属配合物通过熔点、溶解度、颜色、傅里叶变换红外分析和 XRD 进行了表征。对这些产品进行了抗菌活性及其他可利用的应用研究。

  DOI：

  10.14233/ajchem.2015.17807

文献信息

• Discovery and characterization of novel allosteric FAK inhibitors
  作者：Misa Iwatani、Hidehisa Iwata、Atsutoshi Okabe、Robert J. Skene、Naoki Tomita、Yoko Hayashi、Yoshio Aramaki、David J. Hosfield、Akira Hori、Atsuo Baba、Hiroshi Miki

  DOI：10.1016/j.ejmech.2012.06.035

  日期：2013.3

  Focal adhesion kinase (FAR) regulates cell survival and proliferation pathways. Here we report the discovery of a highly selective series of 1,5-dihydropyrazolo[4,3-c][2,1]benzothiazines that demonstrate a novel mode of allosteric inhibition of FAR. These compounds showed slow dissociation from unphosphorylated FAR and were noncompetitive with ATP after long preincubation. Co-crystal structural analysis revealed that the compounds target a novel allosteric site within the C-lobe of the kinase domain, which induces disruption of ATP pocket formation leading to the inhibition of kinase activity. The potency of allosteric inhibition was reduced by phosphorylation of FAR. Coupled SAR analysis revealed that N-substitution of the fused pyrazole is critical to achieve allosteric binding and high selectivity among kinases. (C) 2012 Elsevier Masson SAS. All rights reserved.
• Shafiq, Muhammad; Khan, Islam Ullah; Arshad, Muhammad Nadeem, Asian Journal of Chemistry, 2011, vol. 23, # 5, p. 2101 - 2105
  作者：Shafiq, Muhammad、Khan, Islam Ullah、Arshad, Muhammad Nadeem、Siddiqui, Waseeq Ahmad

  DOI：——

  日期：——