N-(3-bromo-2-methylphenyl)benzamide | 51489-11-3

• 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: N-(3-bromo-2-methylphenyl)benzamide
• CAS: 51489-11-3
• 化学式: C₁₄H₁₂BrNO
• mdl: MFCD02673639
• 分子量: 290.159
• InChiKey: ANGKQCYXVHFALV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  17
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.071
• 拓扑面积：
  29.1
• 氢给体数：
  1
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  N-(3-bromo-2-methylphenyl)benzamide 在 bis-triphenylphosphine-palladium(II) chloride 、 potassium phosphate 、 四(三苯基膦)钯 、 potassium phenolate 、 三苯基膦 、 三氟乙酸 、 potassium bromide 作用下， 以 乙醇 、 水 、 甲苯 为溶剂， 反应 18.0h， 生成 N-(2-methyl-3-(4-((4-(morpholine-4-carbonyl)phenyl)amino)-1H-imidazo[4,5-c]pyridin-6-yl)phenyl)benzamide
  参考文献：
  名称：

  1,4,6-三取代的咪唑并[4,5- c ]吡啶类化合物作为布鲁顿酪氨酸激酶的抑制剂

  摘要：

  在本文中，我们报告了一种针对三取代咪唑并[4,5- c ]吡啶的有效合成方法，该吡啶被设计为布鲁顿酪氨酸激酶（BTK）的抑制剂。引入了两种可供选择的合成路线，用于简单制备所需化合物的N 1，C 4，C 6位置的可变取代基，以及易于获得的结构单元。此外，开发的合成方法对于带有咪唑并[4，5- b ]吡啶骨架的异构体化合物是可行的。在基于以往的研究对比期望，咪唑并[4,5- c ^ ]吡啶抑制剂显示出对BTK显著更高的活性相比，它的咪唑并[4,5- b]吡啶异构体。一系列咪唑并[4,5- c ]吡啶化合物的固有SAR研究表明，对于疏水和亲水取代基，C 6取代均具有极高的耐受性。初步的细胞实验表明在Burkitt淋巴瘤和套细胞淋巴瘤细胞系中有选择性的BTK靶向。因此，这些抑制剂可以作为进一步开发的起点，最终导致可以在依鲁替尼治疗失败后使用的BTK抑制剂。

  DOI：

  10.1016/j.ejmech.2020.113094
• 作为产物：
  描述：

  苯甲酸 在 草酰氯 、 N,N-二异丙基乙胺 、 N,N-二甲基甲酰胺 作用下， 以 二氯甲烷 为溶剂， 反应 4.17h， 生成 N-(3-bromo-2-methylphenyl)benzamide
  参考文献：
  名称：

  Discovery of N-(3-(5-((3-acrylamido-4-(morpholine-4-carbonyl)phenyl)amino)-1-methyl-6-oxo-1,6-dihydropyridin-3-yl)-2-methylphenyl)-4-(tert-butyl)benzamide (CHMFL-BTK-01) as a highly selective irreversible Bruton's tyrosine kinase (BTK) inhibitor

  摘要：

  Currently there are several irreversible BTK inhibitors targeting Cys481 residue under preclinical or clinical development. However, most of these inhibitors also targeted other Idnases such as BMX, JAK3, and EGFR that bear the highly similar active cysteine residues. Through a structure-based drug design approach, we discovered a highly potent (IC50: 7 nM) irreversible BTK inhibitor compound 9 (CHMFL-BTK-01), which displayed a high selectivity profile in KINOMEscan (S score (35) = 0.00) among 468 kinases/mutants at the concentration of 1 mu M. Compound 9 completely abolished BMX, JAK3 and EGFR's activity. Both X-ray crystal structure and cysteine-serine mutation mediated rescue experiment confirmed 9's irreversible binding mode. 9 also potently inhibited BTK Y223 auto-phosphorylation (EC50: <30 nM), arrested cell cycle in G0/G1 phase and induced apoptosis in U2932 and Pfeiffer cells. We believe these features would make 9 a good pharmacological tool to study the BTK related pathology. (C) 2017 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2017.03.001

文献信息

• Discovery of N-(3-(5-((3-acrylamido-4-(morpholine-4-carbonyl)phenyl)amino)-1-methyl-6-oxo-1,6-dihydropyridin-3-yl)-2-methylphenyl)-4-(tert-butyl)benzamide (CHMFL-BTK-01) as a highly selective irreversible Bruton's tyrosine kinase (BTK) inhibitor
  作者：Qianmao Liang、Yongfei Chen、Kailin Yu、Cheng Chen、Shouxiang Zhang、Aoli Wang、Wei Wang、Hong Wu、Xiaochuan Liu、Beilei Wang、Li Wang、Zhenquan Hu、Wenchao Wang、Tao Ren、Shanchun Zhang、Qingsong Liu、Cai-Hong Yun、Jing Liu

  DOI：10.1016/j.ejmech.2017.03.001

  日期：2017.5

  Currently there are several irreversible BTK inhibitors targeting Cys481 residue under preclinical or clinical development. However, most of these inhibitors also targeted other Idnases such as BMX, JAK3, and EGFR that bear the highly similar active cysteine residues. Through a structure-based drug design approach, we discovered a highly potent (IC50: 7 nM) irreversible BTK inhibitor compound 9 (CHMFL-BTK-01), which displayed a high selectivity profile in KINOMEscan (S score (35) = 0.00) among 468 kinases/mutants at the concentration of 1 mu M. Compound 9 completely abolished BMX, JAK3 and EGFR's activity. Both X-ray crystal structure and cysteine-serine mutation mediated rescue experiment confirmed 9's irreversible binding mode. 9 also potently inhibited BTK Y223 auto-phosphorylation (EC50: <30 nM), arrested cell cycle in G0/G1 phase and induced apoptosis in U2932 and Pfeiffer cells. We believe these features would make 9 a good pharmacological tool to study the BTK related pathology. (C) 2017 Elsevier Masson SAS. All rights reserved.
• 1,4,6-Trisubstituted imidazo[4,5-c]pyridines as inhibitors of Bruton’s tyrosine kinase
  作者：Soňa Krajčovičová、Radek Jorda、David Vanda、Miroslav Soural、Vladimír Kryštof

  DOI：10.1016/j.ejmech.2020.113094

  日期：2021.2

  bearing imidazo [4,5-b]pyridine scaffolds. In contrast to expectations based on previous studies, the imidazo [4,5-c]pyridine inhibitor exhibited a significantly higher activity against BTK compared to its imidazo [4,5-b]pyridine isomer. An inherent SAR study in the series of imidazo [4,5-c]pyridine compounds revealed a remarkably high tolerance of C6 substitutions for both hydrophobic and hydrophilic

  在本文中，我们报告了一种针对三取代咪唑并[4,5- c ]吡啶的有效合成方法，该吡啶被设计为布鲁顿酪氨酸激酶（BTK）的抑制剂。引入了两种可供选择的合成路线，用于简单制备所需化合物的N 1，C 4，C 6位置的可变取代基，以及易于获得的结构单元。此外，开发的合成方法对于带有咪唑并[4，5- b ]吡啶骨架的异构体化合物是可行的。在基于以往的研究对比期望，咪唑并[4,5- c ^ ]吡啶抑制剂显示出对BTK显著更高的活性相比，它的咪唑并[4,5- b]吡啶异构体。一系列咪唑并[4,5- c ]吡啶化合物的固有SAR研究表明，对于疏水和亲水取代基，C 6取代均具有极高的耐受性。初步的细胞实验表明在Burkitt淋巴瘤和套细胞淋巴瘤细胞系中有选择性的BTK靶向。因此，这些抑制剂可以作为进一步开发的起点，最终导致可以在依鲁替尼治疗失败后使用的BTK抑制剂。