6-bromobenzofuran-3-carboxylic acid | 1393570-42-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并呋喃
• 英文名称: 6-bromobenzofuran-3-carboxylic acid
• 英文别名: 6-Bromo-1-benzofuran-3-carboxylic acid；6-bromo-1-benzofuran-3-carboxylic acid
• CAS: 1393570-42-7
• 化学式: C₉H₅BrO₃
• 分子量: 241.041
• InChiKey: NWNPYUMOFOZKJH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  13
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  50.4
• 氢给体数：
  1
• 氢受体数：
  3

安全信息

• 储存条件：
  存储在室温下

反应信息

• 作为反应物：
  描述：

  6-bromobenzofuran-3-carboxylic acid 在 草酰氯 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 1.0h， 生成
  参考文献：
  名称：

  Potent BRAF kinase inhibitors based on 2,4,5-trisubstituted imidazole with naphthyl and benzothiophene 4-substituents

  摘要：

  The RAS-RAF-MEK-ERK pathway is hyperactivated in 30% of human cancers. BRAF is a serine-threonine kinase, belonging to this pathway that is mutated with high frequency in human melanoma and other cancers thus BRAF is an important therapeutic target in melanoma. We have designed inhibitors of BRAF based on 2,4,5-trisubstituted imidazoles with naphthyl and benzothiophene-4-substituents. Two compounds were discovered to be potent BRAF inhibitors: 1-(6-{2-[4-(2-dimethylamino-ethoxy) phenyl]-5-(pyridin-4-yl)-1H-imidazol-4-yl} benzo[b]thiophen-3-yl)-2,2,2-trifluoroethanol (1i) with BRAF IC50 = 190 nM and with cellular GI(50) = 2100 nM, and 6-{2-[4-(2-dimethylamino-ethoxy)-phenyl]-5-pyridin-4-yl-3H-imidazol-4-yl}-naphthalen-1-ol (1q) with IC50 = 9 nM and GI(50) = 220 nM. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2012.12.035
• 作为产物：
  描述：

  4-溴-2-羟基苯甲醛 在 三氟化硼乙醚 、 sodium hydroxide 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 反应 3.2h， 生成 6-bromobenzofuran-3-carboxylic acid
  参考文献：
  名称：

  Potent BRAF kinase inhibitors based on 2,4,5-trisubstituted imidazole with naphthyl and benzothiophene 4-substituents

  摘要：

  The RAS-RAF-MEK-ERK pathway is hyperactivated in 30% of human cancers. BRAF is a serine-threonine kinase, belonging to this pathway that is mutated with high frequency in human melanoma and other cancers thus BRAF is an important therapeutic target in melanoma. We have designed inhibitors of BRAF based on 2,4,5-trisubstituted imidazoles with naphthyl and benzothiophene-4-substituents. Two compounds were discovered to be potent BRAF inhibitors: 1-(6-{2-[4-(2-dimethylamino-ethoxy) phenyl]-5-(pyridin-4-yl)-1H-imidazol-4-yl} benzo[b]thiophen-3-yl)-2,2,2-trifluoroethanol (1i) with BRAF IC50 = 190 nM and with cellular GI(50) = 2100 nM, and 6-{2-[4-(2-dimethylamino-ethoxy)-phenyl]-5-pyridin-4-yl-3H-imidazol-4-yl}-naphthalen-1-ol (1q) with IC50 = 9 nM and GI(50) = 220 nM. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2012.12.035

文献信息

• Synthesis, structure-activity relationship and antiviral activity of indole-containing inhibitors of Flavivirus NS2B-NS3 protease
  作者：Shenyou Nie、Jidong Zhao、Xiaowei Wu、Yuan Yao、Fangrui Wu、Yi-Lun Lin、Xin Li、Alexander R. Kneubehl、Megan B. Vogt、Rebecca Rico-Hesse、Yongcheng Song

  DOI：10.1016/j.ejmech.2021.113767

  日期：2021.12

  structure-activity relationships of these and related compounds are discussed. Enzyme kinetics studies show the inhibitor 66 most likely exhibited a non-competitive mode of inhibition. In addition, this series of ZVpro inhibitors also inhibit the NS2B-NS3 protease of dengue and West Nile virus with reduced potencies. The most potent compounds 66 and 67 strongly inhibited Zika virus replication in cells with EC68

  寨卡病毒属于 RNA 病毒的黄病毒家族，其中包括其他重要的人类病原体，例如登革热和西尼罗河病毒。这些病毒没有经过批准的抗病毒药物。黄病毒的高度保守的 NS2B-NS3 蛋白酶对于这些病毒的复制是必不可少的，因此它是药物靶标。化合物筛选后进行药物化学优化产生了一系列新型 2,6-二取代吲哚化合物，它们是寨卡病毒蛋白酶 (ZVpro) 的有效抑制剂，IC 50值低至 320 nM。讨论了这些和相关化合物的构效关系。酶动力学研究表明抑制剂66最有可能表现出非竞争性抑制模式。此外，该系列 ZVpro 抑制剂还抑制登革热和西尼罗河病毒的 NS2B- 蛋白酶，但效力降低。最有效的化合物66和67强烈抑制寨卡病毒在细胞中的复制，EC 68值为 1–3 μM。这些化合物是针对寨卡病毒进一步药物开发的新药理学线索。
• Discovery, Structure–Activity Relationship and In Vitro Anticancer Activity of Small-Molecule Inhibitors of the Protein–Protein Interactions between AF9/ENL and AF4 or DOT1L
  作者：Xin Li、Xiaowei Wu、Shenyou Nie、Jidong Zhao、Yuan Yao、Fangrui Wu、Chandra Bhushan Mishra、Md Ashraf-Uz-Zaman、Bala Krishna Moku、Yongcheng Song

  DOI：10.3390/cancers15215283

  日期：——

  between the most frequent MLL fusion partner proteins AF9/ENL and AF4 or histone methyltransferase DOT1L are drug targets for MLL-rearranged (MLL-r) leukemia. Several benzothiophene-carboxamide compounds were identified as novel inhibitors of these PPIs with IC50 values as low as 1.6 μM. Structure-activity relationship studies of 77 benzothiophene and related indole and benzofuran compounds show that

  涉及混合谱系白血病 (MLL) 基因的染色体易位导致 5-10% 的急性白血病，且临床结果不佳。最常见的 MLL 融合伴侣蛋白 AF9/ENL 和 AF4 或组蛋白甲基转移酶 DOT1L 之间的蛋白质-蛋白质相互作用 (PPI) 是 MLL 重排 (MLL-r) 白血病的药物靶点。几种苯并噻吩甲酰胺化合物被鉴定为这些 PPI 的新型抑制剂，IC50 值低至 1.6 μM。对 77 种苯并噻吩以及相关吲哚和苯并呋喃化合物的构效关系研究表明，4-哌啶-1-基苯基或 4-吡咯烷-1-基苯基取代基对于活性至关重要。该抑制剂抑制MLL靶基因HoxA9、Meis1和Myc的表达，并选择性抑制MLL-r和其他急性髓系白血病细胞的增殖，EC50值低至4.7 μM。这些抑制剂是 AF9/ENL 生物学研究的有用化学探针，也是进一步开发针对 MLL-r 和其他白血病的药物的药理学先导物。
• WO2020010252A5
  申请人：——

  公开号：WO2020010252A5

  公开（公告）日：2022-07-05
• FUSED RING COMPOUND HAVING UREA STRUCTURE
  申请人：Sanford Burnham Prebys Medical Discovery Institute

  公开号：EP3818053A1

  公开（公告）日：2021-05-12