3-(1H-benzimidazol-2-yl)-5-bromo-1H-pyrazolo[3,4-b]pyridine | 1346169-43-4

• 分子结构分类: 有机化合物 - 有机杂环化合物
• 英文名称: 3-(1H-benzimidazol-2-yl)-5-bromo-1H-pyrazolo[3,4-b]pyridine
• 英文别名: 3-(1H-benzimidazol-2-yl)-5-bromo-2H-pyrazolo[3,4-b]pyridine
• CAS: 1346169-43-4
• 化学式: C₁₃H₈BrN₅
• 分子量: 314.144
• InChiKey: JTAADZNAHUTEDB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  19
• 可旋转键数：
  1
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  70.2
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3-(1H-benzimidazol-2-yl)-5-bromo-1H-pyrazolo[3,4-b]pyridine 、 [RuCl(μ-Cl)(4-formylphenoxyacetyl-η6-benzylamide)]2*0.5H2O 以 乙醇 为溶剂， 以92%的产率得到[RuCl(4-formylphenoxyacetyl-η6-benzylamide)(3-(1H-benzimidazol-2-yl)-5-bromo-1H-pyrazolo[3,4-b]pyridine(-1H))]*H2O
  参考文献：
  名称：

  Conjugation of Organoruthenium(II) 3-(1H-Benzimidazol-2-yl)pyrazolo[3,4-b]pyridines and Indolo[3,2-d]benzazepines to Recombinant Human Serum Albumin: a Strategy To Enhance Cytotoxicity in Cancer Cells

  摘要：

  Following our strategy of coupling cyclin-dependent kinase (Cdk) inhibitors with organometallic moieties to improve their physicochemical properties and bioavailability, five organoruthenium complexes (1c-5c) of the general formula [RuCl(eta(6)-arene)(L)]Cl have been synthesized in which the arene is 4-formylphenoxyacetyl-eta(6)-benzylamide and L is a Cdk inhibitor [3-(1H-benzimidazol-2-yl)-1H-pyrazolo[3,4-b]pyridines (L1-L3) and indolo[3,2-d]benzazepines (L4 and L5)]. All of the compounds were characterized by spectroscopic and analytical methods. Upon prolonged standing (2-3 months) at room temperature, the dimethyl sulfoxide (DMSO) solutions of 1c and 2c-(HCl) afforded residues, which after recrystallization from EtOH and EtOH/H2O, respectively, were shown by X-ray diffraction to be cis,cis-[(RuCl2)-Cl-II(DMSO)(2)(L1)]center dot H2O and mer-[(RuCl)-Cl-II(DMSO)(3)(L2-H)]center dot H2O. Compound 5c, with a coordinated amidine unit, undergoes E/Z isomerization in solution. The antiproliferative activities and effects on the cell cycle of the new compounds were evaluated. Complexes 1c-5c are moderately cytotoxic to cancer cells (CH1, SW480, A549, A2780, and A2780cisR cell lines). Therefore, in order to improve their antiproliferative effects, as well as their drug targeting and delivery to cancer cells, 1c-5c were conjugated to recombinant human serum albumin, potentially exploiting the so-called "enhanced permeability and retention" effect that results in the accumulation of macromolecules in tumors. Notably, a marked increase in cytotoxicity of the albumin conjugates was observed in all cases.

  DOI：

  10.1021/ic201801e

文献信息

• Organometallic 3-(1<i>H</i>-Benzimidazol-2-yl)-1<i>H</i>-pyrazolo[3,4-<i>b</i>]pyridines as Potential Anticancer Agents
  作者：Iryna N. Stepanenko、Maria S. Novak、Gerhard Mühlgassner、Alexander Roller、Michaela Hejl、Vladimir B. Arion、Michael A. Jakupec、Bernhard K. Keppler

  DOI：10.1021/ic201704u

  日期：2011.11.21

  of 1H-pyrazolo[3,4-b]pyridine-3-carboxylic acids (1, 3) through the use of an inexpensive coupling reagent, N,N′-carbonyldiimidazole (CDI)). Stabilization of the 7b tautomer of methoxymethyl-substituted L3 by coordination to a metal(II) center, as well as the NMR spectroscopic characterization of two tautomers 7b-L3 and 4b′-L3 in a metal-free state are described. Structure–activity relationships with

  六种通式为 [M II Cl(η 6 - p -cymene)(L)]Cl 的有机金属配合物，其中 M = Ru ( 11a , 12a , 13a ) 或 Os ( 11b , 12b , 13b ) 和 L = 3- (1 H -benzimidazol-2-yl)-1 H -pyrazolo[3,4- b ]pyridines ( L1 – L3) 已合成。后者被称为潜在的细胞周期蛋白依赖性激酶 (Cdk) 抑制剂。所有化合物都已通过元素分析、一维和二维 NMR 光谱、UV-vis 光谱、ESI 质谱和 X 射线晶体学进行了全面表征（11b和12b）。3-(1 H -benzimidazol-2-yl)-1 H - pyrazolo[3,4- b ]pyridines ( L1 – L3 )的多步合成，由其他研究人员报道，我们基本上已经修改（例如, 5-溴-1 H-吡唑并[3,4- b
• 3-benzoimidazolyl-pyrazolopyridines useful in treating kinase disorders
  申请人：Chiu George

  公开号：US20090048249A1

  公开（公告）日：2009-02-19

  The present invention is directed to novel 3-benzoimidazolyl-pyrazolopyridine compounds of formula (I): and pharmaceutically acceptable forms thereof and their synthesis and use as inhibitors of serine-threonine protein kinases and tyrosine protein kinases and interactions thereof.

  本发明涉及一种新型的3-苯并咪唑基-吡唑吡啶化合物，其化学式为(I)，以及其药学上可接受的形式、合成方法和用作丝氨酸/苏氨酸蛋白激酶和酪氨酸蛋白激酶的抑制剂及其相互作用的用途。
• US7541367B2
  申请人：——

  公开号：US7541367B2

  公开（公告）日：2009-06-02
• [EN] 3-BENZOIMIDAZOLYL-PYRAZOLOPYRIDINES USEFUL IN TREATING KINASE DISORDERS<br/>[FR] 3-BENZOIMIDAZOLYL-PYRAZOLOPYRIDINES UTILISEES POUR TRAITER DES TROUBLES DONT LA MEDIATION EST ASSUREE PAR DES KINASES
  申请人：JANSSEN PHARMACEUTICA NV

  公开号：WO2006130673A1

  公开（公告）日：2006-12-07

  [EN] The present invention is directed to novel 3-benzoimidazolyl-pyrazolopyridine compounds of formula (I): and pharmaceutically acceptable forms thereof and their synthesis and use as inhibitors of serine-threonine protein kinases and tyrosine protein kinases and interactions thereof.
  [FR] L'invention concerne de nouveaux composés 3-benzoimidazolyl-pyrazolopyridine de formule (I), et des formes pharmaceutiquement acceptables de ces composés. La présente invention concerne également la synthèse et l'utilisation desdits composés en tant qu'inhibiteurs des protéines kinases sérine-thréonine et des protéines kinases tyrosine et des interactions correspondantes.