3,6-dibromobenzo[b]thiophene | 1426082-37-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并噻吩类
• 英文名称: 3,6-dibromobenzo[b]thiophene
• 英文别名: 3,6-Dibromobenzo[B]thiophene；3,6-dibromo-1-benzothiophene
• CAS: 1426082-37-2
• 化学式: C₈H₄Br₂S
• 分子量: 291.994
• InChiKey: LQQHIORRVCHCNT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  11
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  28.2
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  3,6-dibromobenzo[b]thiophene 在 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 、 正丁基锂 、 potassium acetate 作用下， 以 乙醚 、 正己烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 5.25h， 生成 6-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-benzo[b]thiophene-3-carbaldehyde
  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：

  6-溴苯并[b]噻吩-2-甲酸 在 喹啉 、 N-溴代丁二酰亚胺(NBS) 、 铜 、 溶剂黄146 作用下， 以 氯仿 为溶剂， 反应 2.0h， 生成 3,6-dibromobenzo[b]thiophene
  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 of C2 Substituted Benzothiophenes via an Interrupted Pummerer/[3,3]-Sigmatropic/1,2-Migration Cascade of Benzothiophene <i>S</i> -Oxides
  作者：Zhen He、Harry J. Shrives、José A. Fernández-Salas、Alberto Abengózar、Jessica Neufeld、Kevin Yang、Alexander P. Pulis、David J. Procter

  DOI：10.1002/anie.201801982

  日期：2018.5.14

  Functionalized benzothiophenes are important scaffolds found in molecules with wide ranging biological activity and in organic materials. We describe an efficient, metal‐free synthesis of C2 arylated, allylated, and propargylated benzothiophenes. The reaction utilizes synthetically unexplored yet readily accessible benzothiophene S‐oxides and phenols, allyl‐, or propargyl silanes in a unique cascade

  功能化的苯并噻吩是在具有广泛生物活性的分子和有机材料中发现的重要支架。我们描述了一种高效，无金属的C2芳基化，烯丙基化和炔丙基化苯并噻吩的合成方法。该反应以独特的级联顺序利用合成的未探索但易于获得的苯并噻吩S-氧化物和苯酚，烯丙基或炔丙基硅烷。苯并噻吩S-氧化物与偶合剂之间的Pummerer反应中断，生成的aromatic盐缺乏芳香性，因此容易实现[3,3]-σ重排。随后生成的苯并噻吩盐经历了以前未经探索的1,2-迁移，以进入C2功能化的苯并噻吩。
• 3,9-Disubstituted Bis[1]benzothieno[3,2-<i>b</i>;2′,3′-<i>e</i>][1,4]thiazines with Low Oxidation Potentials and Enhanced Emission
  作者：Henning R. V. Berens、Kausar Mohammad、Guido J. Reiss、Thomas J. J. Müller

  DOI：10.1021/acs.joc.1c00397

  日期：2021.6.18

  mino substituted BBTT possess very high lying HOMO energy (EHOMO = −4.46 to −4.83 eV), a favorable property of hole transport molecules. A representative X-ray structure analysis reveals that the central BBTT core in these extended π-systems is essentially planarized. Upon protonation of a 3,9-bis(di(hetero)arylamino) substituted BBTT, the absorption color shifts from yellow to deep blue with a concomitant

  二溴化双[1]苯并噻吩并[3,2- b ;2',3'- e ][1,4]噻嗪（BBTT）被有效合成并应用于铃木和Buchwald-Hartwig交叉偶联反应中，以获得3具有扩展的 π 共轭和增强的电子特性的 ,9-二取代 BBTT 衍生物。例如，3,9-二（杂）芳基取代的 BBTT 衍生物优于它们的母体同系物吩噻嗪，具有较低的氧化电位和明显的黄色至橙红色荧光（Φ f ≈ 30-45%）。此外，3,9-双(二(杂)芳基氨基取代的BBTT)具有非常高的HOMO能( E HOMO= -4.46 至 -4.83 eV），这是空穴传输分子的有利特性。代表性的 X 射线结构分析表明，这些扩展 π 系统中的中央 BBTT 核心基本上是平面化的。在 3,9-双（二（杂）芳基氨基）取代的 BBTT 质子化后，吸收颜色从黄色变为深蓝色，伴随着发射损失。这些新型 BBTT 衍生物的光学性质可以通过时间相关密度泛函理论
• Discovery of Thieno[2,3-<i>e</i>]indazole Derivatives as Novel Oral Selective Estrogen Receptor Degraders with Highly Improved Antitumor Effect and Favorable Druggability
  作者：Zhengyu Lu、Yangzhi Cao、Dan Zhang、Xin Meng、Bin Guo、Deyu Kong、Yushe Yang

  DOI：10.1021/acs.jmedchem.2c00008

  日期：2022.4.14

  Endocrine therapies in the treatment of early and metastatic estrogen receptor α positive (ERα+) breast cancer (BC) are greatly limited by de novo and acquired resistance. Selective estrogen receptor degraders (SERDs) like fulvestrant provide new strategies for endocrine therapy combinations due to unique mechanisms. Herein, we disclose our structure-based optimization of LSZ102 by replacing 6-hydroxybenzothiophene

  内分泌治疗在早期和转移性雌激素受体 α 阳性 (ERα+) 乳腺癌 (BC) 的治疗中受到新发耐药和获得性耐药的极大限制。由于独特的机制，选择性雌激素受体降解剂 (SERD) （如氟维司群）为内分泌治疗组合提供了新策略。在此，我们通过用 6 H-噻吩并[2,3 - e ]吲唑代替 6-羟基苯并噻吩，公开了基于结构的 LSZ102 优化。随后的丙烯酸 degron 修饰使我们将化合物40确定为首选候选者。一般来说，化合物40显示出比先导 LSZ102 更好的药理学特征，表现出对野生型或他莫昔芬抗性 MCF-7 细胞的生长抑制，有效的 ERα 降解，以及优越的药代动力学特性，包括大脑在内的定向靶组织分布，以及强大的抗肿瘤功效小鼠乳腺癌异种移植模型。目前，40 个正在临床前试验中进行评估。
• [EN] SUBSTITUTED BENZOTHIOPHENE DERIVATIVES AND METHODS OF USE THEREOF<br/>[FR] DÉRIVÉS DE BENZOTHIOPHÈNE SUBSTITUÉS ET LEURS PROCÉDÉS D'UTILISATION
  申请人：MERCK SHARP & DOHME LLC

  公开号：WO2023121939A1

  公开（公告）日：2023-06-29

  Provided are novel Substituted Thiophene Derivatives of Formula (I) and pharmaceutically acceptable salts thereof, wherein R1, R2, R3, R4, and R7are as defined herein, as well as compositions comprising at least one Substituted Thiophene Derivative, and methods of using the Substituted Thiophene Derivatives for treating or preventing cancer in a patient.

  本文提供了新颖的式 (I) 取代的噻吩衍生物及其药学上可接受的盐，其中 R1、R2、R3、R4 和 R7 如本文所定义；还提供了包含至少一种取代的噻吩衍生物的组合物，以及使用取代的噻吩衍生物治疗或预防患者癌症的方法。
• NaBH4-TMEDA and a palladium catalyst as efficient regio- and chemoselective system for the hydrodehalogenation of halogenated heterocycles
  作者：Giorgio Chelucci、Susanna Figus

  DOI：10.1016/j.molcata.2014.06.012

  日期：2014.11