4-bromo-1-phenylsulfonyl-1H-indole-2-carboxylic acid | 896137-75-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: 4-bromo-1-phenylsulfonyl-1H-indole-2-carboxylic acid
• 英文别名: 1-(Benzenesulfonyl)-4-bromoindole-2-carboxylic acid
• CAS: 896137-75-0
• 化学式: C₁₅H₁₀BrNO₄S
• 分子量: 380.219
• InChiKey: BJAOKALFLKKIDD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  22
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  84.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-bromo-1-phenylsulfonyl-1H-indole-2-carboxylic acid 在 氯化亚砜 作用下， 反应 1.0h， 以99%的产率得到1-benzenesulfonyl-4-bromo-1H-indole-2-carbonyl chloride
  参考文献：
  名称：

  Novel Bis(1H-indol-2-yl)methanones as Potent Inhibitors of FLT3 and Platelet-Derived Growth Factor Receptor Tyrosine Kinase

  摘要：

  FLT3 receptor tyrosine kinase is aberrantly active in many cases of acute myeloid leukemia (AML). Recently, bis(1H-indol-2-yl) methanones were found to inhibit FLT3 and PDGFR kinases. To optimize FLT3 activity and selectivity, 35 novel derivatives were synthesized and tested for inhibition of FLT3 and PDGFR autophosphorylation. The most potent FLT3 inhibitors 98 and 102 show IC50 values of 0.06 and 0.04 mu M, respectively, and 1 order of magnitude lower PDGFR inhibiting activity. The derivatives 76 and 82 are 20- to 40- fold PDGFR selective. Docking at the recent FLT3 structure suggests a bidentate binding mode with the backbone of Cys-694. Activity and selectivity can be related to interactions of one indole moiety with a hydrophobic pocket including Phe-691, the only different binding site residue (PDGFR Thr-681). Compound 102 inhibited the proliferation of 32D cells expressing wildtype FLT3 or FLT3-ITD similarly as FLT3 autophosphorylation, and induced apoptosis in primary AML patient blasts.

  DOI：

  10.1021/jm058033i
• 作为产物：
  描述：

  4-溴吲哚 在 sodium hydride 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 正庚烷 为溶剂， 反应 4.0h， 生成 4-bromo-1-phenylsulfonyl-1H-indole-2-carboxylic acid
  参考文献：
  名称：

  Novel Bis(1H-indol-2-yl)methanones as Potent Inhibitors of FLT3 and Platelet-Derived Growth Factor Receptor Tyrosine Kinase

  摘要：

  FLT3 receptor tyrosine kinase is aberrantly active in many cases of acute myeloid leukemia (AML). Recently, bis(1H-indol-2-yl) methanones were found to inhibit FLT3 and PDGFR kinases. To optimize FLT3 activity and selectivity, 35 novel derivatives were synthesized and tested for inhibition of FLT3 and PDGFR autophosphorylation. The most potent FLT3 inhibitors 98 and 102 show IC50 values of 0.06 and 0.04 mu M, respectively, and 1 order of magnitude lower PDGFR inhibiting activity. The derivatives 76 and 82 are 20- to 40- fold PDGFR selective. Docking at the recent FLT3 structure suggests a bidentate binding mode with the backbone of Cys-694. Activity and selectivity can be related to interactions of one indole moiety with a hydrophobic pocket including Phe-691, the only different binding site residue (PDGFR Thr-681). Compound 102 inhibited the proliferation of 32D cells expressing wildtype FLT3 or FLT3-ITD similarly as FLT3 autophosphorylation, and induced apoptosis in primary AML patient blasts.

  DOI：

  10.1021/jm058033i

文献信息

• [EN] INHIBITORS OF BRUTON'S TYROSINE KINASE<br/>[FR] INHIBITEURS DE LA TYROSINE KINASE DE BRUTON
  申请人：HOFFMANN LA ROCHE

  公开号：WO2015086635A1

  公开（公告）日：2015-06-18

  This application discloses compounds according to generic Formula (I): wherein all variables are defined as described herein, which inhibit Btk. The compounds disclosed herein are useful to modulate the activity of Btk and treat diseases associated with excessive Btk activity. The compounds are useful for the treatment of oncological, auto-immune, and inflammatory diseases caused by aberrant B-cell activation. Also disclosed are compositions containing compounds of Formula (I) and at least one carrier, diluent or excipient.

  本申请揭示了根据通用式（I）定义的化合物，其中所有变量如本文所述，这些化合物抑制Btk。本文披露的化合物可用于调节Btk的活性并治疗与过度Btk活性相关的疾病。这些化合物可用于治疗由异常B细胞激活引起的肿瘤学、自身免疫和炎症性疾病。还披露了包含通用式（I）化合物和至少一种载体、稀释剂或赋形剂的组合物。
• INHIBITORS OF BRUTON'S TYROSINE KINASE
  申请人：F. Hoffmann-La Roche AG

  公开号：EP3080097B1

  公开（公告）日：2018-04-18
• US9624201B2
  申请人：——

  公开号：US9624201B2

  公开（公告）日：2017-04-18