2-bromo-1-(2,6-difluoro-4-methoxyphenyl)ethanone | 490038-74-9

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 2-bromo-1-(2,6-difluoro-4-methoxyphenyl)ethanone
• 英文别名: 2',6'-Difluoro-4'-methoxyphenacyl bromide
• CAS: 490038-74-9
• 化学式: C₉H₇BrF₂O₂
• 分子量: 265.054
• InChiKey: ZEMJOIJNEFNPBU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  14
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  26.3
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-bromo-1-(2,6-difluoro-4-methoxyphenyl)ethanone 在 水 、 乙酸乙酯 、 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 22.0h， 生成 [2-Amino-6-(2,6-difluoro-benzoyl)-imidazo[1,2-a]pyridin-3-yl]-(2,6-difluoro-4-methoxy-phenyl)-methanone
  参考文献：
  名称：

  A New Approach to the Synthesis of 2-Aminoimidazo[1,2-a]pyridineDerivatives Through Rapid Parallel Synthesis

  摘要：

  利用快速平行合成法制备出了不同取代的 6-（2,6-二氟苯甲酰基）咪唑并吡啶 3。关键的氰酰胺中间体 4 由氯吡啶 1 制备，并与不同的溴苯乙酮（也是通过快速平行合成法制备的）在环内氮处发生烷基化反应。随后用 EtOAc/H2O 原位环化，得到目标分子。

  DOI：

  10.1055/s-2002-33539
• 作为产物：
  描述：

  3,5-二氟苯甲醚 在 aluminum (III) chloride tetra-N-butylammonium tribromide 作用下， 以 二氯甲烷 、 乙腈 为溶剂， 反应 18.5h， 生成 2-bromo-1-(2,6-difluoro-4-methoxyphenyl)ethanone
  参考文献：
  名称：

  Modulators Of HEC1 Activity And Methods Therefor

  摘要：

  提供了用于调节Hec1/Nek2相互作用的化合物、组合物和方法。特别偏爱的化合物会破坏Nek2/Hec1的结合，因此可用作肿瘤疾病的化疗药物。

  公开号：

  US20110230486A1

文献信息

• Synthesis and biological evaluation of N-(4-phenylthiazol-2-yl)cinnamamide derivatives as novel potential anti-tumor agents
  作者：Yong Luo、Yongxia Zhu、Kai Ran、Zhihao Liu、Ningyu Wang、Qiang Feng、Jun Zeng、Lidan Zhang、Bing He、Tinghong Ye、Shirui Zhu、Xiaolong Qiu、Luoting Yu

  DOI：10.1039/c4md00573b

  日期：——

  In this study, a series of novel N-(4-phenylthiazol-2-yl)-cinnamamide derivatives (7a–8n) were synthesized and evaluated for their anti-proliferative activities in vitro.

  在这项研究中，合成了一系列新型的N-(4-苯基噻唑-2-基)-肉桂酰胺衍生物（7a–8n），并评估了它们在体外对细胞增殖的抑制活性。
• Modulators Of HEC1 Activity And Methods Therefor
  申请人：Lau Johnson

  公开号：US20110230486A1

  公开（公告）日：2011-09-22

  Compounds, compositions, and methods for modulation of Hec1/Nek2 interaction are provided. Especially preferred compounds disrupt Nek2/Hec1 binding and are therefore useful as chemotherapeutic agent for neoplastic diseases.

  提供了用于调节Hec1/Nek2相互作用的化合物、组合物和方法。特别偏爱的化合物会破坏Nek2/Hec1的结合，因此可用作肿瘤疾病的化疗药物。
• Aminoimidazo[1,2-a]pyridines as a new structural class of cyclin-dependent kinase inhibitors. Part 1: Design, synthesis, and biological evaluation
  作者：Carlos Jaramillo、J. Eugenio de Diego、Chafiq Hamdouchi、Elizabeth Collins、Heather Keyser、Concha Sánchez-Martı́nez、Miriam del Prado、Bryan Norman、Harold B. Brooks、Scott A. Watkins、Charles D. Spencer、Jack Alan Dempsey、Bryan D. Anderson、Robert M. Campbell、Tellie Leggett、Bharvin Patel、Richard M. Schultz、Juan Espinosa、Michal Vieth、Faming Zhang、David E. Timm

  DOI：10.1016/j.bmcl.2004.09.053

  日期：2004.12

  We have identified a novel structural class of protein serine/threonine kinase inhibitors comprised of an aminoimidazo[1,2-a]pyridine nucleus. Compounds from this family are shown to potently inhibit cyclin-dependent kinases by competing with ATP for binding to a catalytic subunit of the protein. Structure-based design approach was used to direct this chemical scaffold toward generating potent and

  我们已经确定了由氨基咪唑并[1,2-a]吡啶核组成的蛋白质丝氨酸/苏氨酸激酶抑制剂的新型结构类别。已显示该家族化合物通过与ATP竞争结合蛋白的催化亚基而有效抑制细胞周期蛋白依赖性激酶。基于结构的设计方法用于指导该化学支架产生有效的和选择性的CDK2抑制剂。这类新型的ATP定位的蛋白激酶抑制剂氨基咪唑并[1,2-a]吡啶类化合物的发现，为寻求有效治疗癌症和其他涉及蛋白激酶信号传导途径的疾病的药物化学工具提供了基础。
• MODULATORS OF HEC1 ACTIVITY AND METHODS THEREFOR
  申请人：Taivex Therapeutics, Inc.

  公开号：US20150057281A1

  公开（公告）日：2015-02-26

  Compounds, compositions, and methods for modulation of Hec1/Nek2 interaction are provided. Especially preferred compounds disrupt Nek2/Hec1 binding and are therefore useful as chemotherapeutic agent for neoplastic diseases.

  提供了调节Hec1/Nek2相互作用的化合物、组合物和方法。特别优选的化合物破坏Nek2/Hec1结合并因此可用作肿瘤疾病的化疗药物。
• Discovery of 4-Aryl-<i>N</i>-arylcarbonyl-2-aminothiazoles as Hec1/Nek2 Inhibitors. Part I: Optimization of in Vitro Potencies and Pharmacokinetic Properties
  作者：Ying-Shuan E. Lee、Shih-Hsien Chuang、Lynn Y. L. Huang、Chun-Liang Lai、Yu-Hsiang Lin、Ju-Ying Yang、Chia-Wei Liu、Sheng-chuan Yang、Her-Sheng Lin、Chia-chi Chang、Jun-Yu Lai、Pei-Shiou Jian、King Lam、Jia-Ming Chang、Johnson Y. N. Lau、Jiann-Jyh Huang

  DOI：10.1021/jm401990s

  日期：2014.5.22

  A series of 4-aryl-N-arylcarbonyl-2-aminothiazoles of scaffold 4 was designed and synthesized as Hec1/Nek2 inhibitors. Structural optimization of 4 led to compound S 32 bearing C-4' 4-methoxyphenoxy and 4-(o-fluoropyridyl)-carbonyl groups that showed low nanomolar in vitro antiproliferative activity (IC50: 16.3-42.7 nM), high intravenous AUC (64.9 mu M.h, 2.0 mg/kg) in SD rats, and significant in vivo antitumor activity (T/C = 32%, 20 mg/kg, IV) in mice bearing human MDA-MB-231 xenografts. Cell responses resulting from Hec1/Nek2 inhibition were observed in cells treated with 32, including a reduced level of Hec1 coimmunoprecipitated with Nek2, degradation of Nek2, mitotic abnormalities, and apoptosis. Compound 32 showed selectivity toward cancer cells over normal phenotype cells and was inactive in a [H-3]astemizole competitive binding assay for hERG liability screening. Therefore, 32 is as a good lead toward the discovery of a preclinical candidate targeting Hec1/Nek2 interaction.