4-(bromoacetyl)-2-phenylquinoline hydrobromide | 5659-02-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: 4-(bromoacetyl)-2-phenylquinoline hydrobromide
• 英文别名: 2-bromo-1-(2-phenyl-4-quinolinyl)ethanone hydrobromide；2-bromo-1-(2-phenyl-[4]quinolyl)-ethanone; hydrobromide；2-Brom-1-(2-phenyl-[4]chinolyl)-aethanon; Hydrobromid；2-Bromo-1-(2-phenylquinolin-4-yl)ethan-1-one hydrobromide；2-bromo-1-(2-phenylquinolin-4-yl)ethanone;hydrobromide
• CAS: 5659-02-9
• 化学式: BrH*C₁₇H₁₂BrNO
• 分子量: 407.104
• InChiKey: VPOAOJNCYSQZSZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.06
• 重原子数：
  21
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  30
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  4-(bromoacetyl)-2-phenylquinoline hydrobromide 、 苯甲脒 在 sodium carbonate 作用下， 以 乙醇 为溶剂， 反应 24.0h， 以70%的产率得到2-phenyl-4-(2-phenyl-1H-imidazol-5-yl)quinoline
  参考文献：
  名称：

  新型 4-杂芳基-2-苯基喹啉的合成及其作为 NK-2/NK-3 受体配体的药理活性

  摘要：

  为了更好地了解构效关系，合成了取代的 4-杂芳基-2-苯基喹啉并在 NK-2 和 NK-3 受体上进行了测试。总的来说，这些可被视为 NK-3 拮抗剂 SB 218795 的生物电子等排体的分子显示出比模板低的活性。环电子分布和H-键供体和受体位置在选择性中起一定作用，2-咪唑基取代的2a主要对NK-3表现出亲和力，而3-吡唑基取代的4表现出与NK-2受体的优先相互作用。合成化合物的结构表征是通过核磁共振和质谱技术实现的。二维 1H-NOESY 实验是确定化合物 9 和 11b – c 的异构结构的有用工具。

  DOI：

  10.1002/ardp.200600113
• 作为产物：
  描述：

  2-苯基-4-喹啉羧酸 在 氯化亚砜 、 N,N-二甲基甲酰胺 作用下， 以 四氢呋喃 、 正己烷 为溶剂， 反应 24.0h， 生成 4-(bromoacetyl)-2-phenylquinoline hydrobromide
  参考文献：
  名称：

  SAR studies of 4-pyridyl heterocyclic anilines that selectively induce autophagic cell death in von Hippel-Lindau-deficient renal cell carcinoma cells

  摘要：

  We recently identified a class of pyridyl aniline thiazoles (PAT) that displayed selective cytotoxicity for von Hippel-Lindau (VHL) deficient renal cell carcinoma (RCC) cells in vitro and in vivo. Structure-activity relationship (SAR) studies were used to develop a comparative molecular field analysis (CoMFA) model that related VHL-selective potency to the three-dimensional arrangement of chemical features of the chemotype. We now report the further molecular alignment-guided exploration of the chemotype to discover potent and selective PAT analogues. The contribution of the central thiazole ring was explored using a series of five-and six-membered ring heterocyclic replacements to vary the electronic and steric interactions in the central unit. We also explored a positive steric CoMFA contour adjacent to the pyridyl ring using Pd-catalysed cross-coupling Suzuki-Miyaura, Sonogashira and nucleophilic displacement reactions to prepare of a series of aryl-, alkynyl-, alkoxy- and alkylamino-substituted pyridines, respectively. In vitro potency and selectivity were determined using paired RCC cell lines: the VHL-null cell line RCC4 and the VHL-positive cell line RCC4-VHL. Active analogues selectively induced autophagy in RCC4 cells. We have used the new SAR data to further develop the CoMFA model, and compared this to a 2D-QSAR method. Our progress towards realising the therapeutic potential of this chemotype as a targeted cytotoxic therapy for the treatment of RCC by exploiting the absence of the VHL tumour suppressor gene is reported. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.04.042

文献信息

• [EN] HETEROARYL COMPOUNDS, COMPOSITIONS, AND METHODS OF USE IN CANCER TREATMENT<br/>[FR] COMPOSÉS HÉTÉROARYLE, COMPOSITIONS ET PROCÉDÉS D'UTILISATION DANS LE TRAITEMENT DU CANCER
  申请人：UNIV LELAND STANFORD JUNIOR

  公开号：WO2009114552A1

  公开（公告）日：2009-09-17

  Provided herein are novel heteroaryl compounds, compositions comprising the compounds, and methods of treatment or prevention comprising administration of the compounds. The compounds are effective in the targeting of cells defective in the von Hippel-Lindau gene and in inducing autophagic cell death. The methods are directed to treating or preventing diseases such as cancer, and in particular cancers resulting from von Hippel-Lindau disease. The compounds of the invention may be administered in combination with another therapeutic agent.

  本文提供了新颖的杂环芳基化合物，包含这些化合物的组合物，以及包括给予这些化合物的治疗或预防方法。这些化合物在靶向冯·希普尔-林道（von Hippel-Lindau）基因缺陷细胞和诱导自噬性细胞死亡方面具有有效性。这些方法旨在治疗或预防癌症等疾病，特别是由冯·希普尔-林道疾病引起的癌症。本发明的化合物可以与另一种治疗剂联合给药。
• HETEROARYL COMPOUNDS, COMPOSITIONS, AND METHODS OF USE IN CANCER TREATMENT
  申请人：Turcotte Sandra

  公开号：US20110105436A1

  公开（公告）日：2011-05-05

  Provided herein are novel heteroaryl compounds, compositions comprising the compounds, and methods of treatment or prevention comprising administration of the compounds. The compounds are effective in the targeting of cells defective in the von Hippel-Lindau gene and in inducing autophagic cell death. The methods are directed to treating or preventing diseases such as cancer, and in particular cancers resulting from von Hippel-Lindau disease. The compounds of the invention may be administered in combination with another therapeutic agent.

  本文提供了新型的杂环芳基化合物、包含这些化合物的组合物以及治疗或预防方法，包括给予这些化合物。这些化合物能够有效地针对von Hippel-Lindau基因缺陷的细胞，并诱导自噬性细胞死亡。这些方法旨在治疗或预防癌症等疾病，特别是由von Hippel-Lindau病引起的癌症。本发明的化合物可以与另一种治疗药物联合使用。
• SAR studies of 4-pyridyl heterocyclic anilines that selectively induce autophagic cell death in von Hippel-Lindau-deficient renal cell carcinoma cells
  作者：Muriel Bonnet、Jack U. Flanagan、Denise A. Chan、Edwin W. Lai、Phuong Nguyen、Amato J. Giaccia、Michael P. Hay

  DOI：10.1016/j.bmc.2011.04.042

  日期：2011.6

  We recently identified a class of pyridyl aniline thiazoles (PAT) that displayed selective cytotoxicity for von Hippel-Lindau (VHL) deficient renal cell carcinoma (RCC) cells in vitro and in vivo. Structure-activity relationship (SAR) studies were used to develop a comparative molecular field analysis (CoMFA) model that related VHL-selective potency to the three-dimensional arrangement of chemical features of the chemotype. We now report the further molecular alignment-guided exploration of the chemotype to discover potent and selective PAT analogues. The contribution of the central thiazole ring was explored using a series of five-and six-membered ring heterocyclic replacements to vary the electronic and steric interactions in the central unit. We also explored a positive steric CoMFA contour adjacent to the pyridyl ring using Pd-catalysed cross-coupling Suzuki-Miyaura, Sonogashira and nucleophilic displacement reactions to prepare of a series of aryl-, alkynyl-, alkoxy- and alkylamino-substituted pyridines, respectively. In vitro potency and selectivity were determined using paired RCC cell lines: the VHL-null cell line RCC4 and the VHL-positive cell line RCC4-VHL. Active analogues selectively induced autophagy in RCC4 cells. We have used the new SAR data to further develop the CoMFA model, and compared this to a 2D-QSAR method. Our progress towards realising the therapeutic potential of this chemotype as a targeted cytotoxic therapy for the treatment of RCC by exploiting the absence of the VHL tumour suppressor gene is reported. (C) 2011 Elsevier Ltd. All rights reserved.
• Synthesis of New 4-Heteroaryl-2-Phenylquinolines and Their Pharmacological Activity as NK-2/NK-3 Receptor Ligands
  作者：Anna Borioni、Carlo Mustazza、Isabella Sestili、Maria Sbraccia、Luciana Turchetto、Maria Rosaria Del Giudice

  DOI：10.1002/ardp.200600113

  日期：2007.1

  Substituted 4‐heteroaryl‐2‐phenylquinolines were synthesized and tested on NK‐2 and NK‐3 receptors in order to get a better insight in the structure‐activity relationship. On the whole, these molecules, which can be regarded as bioisosters of the NK‐3 antagonist SB 218795, displayed a lower activity than the template. Ring electronic distribution and H‐bond donor and acceptor positions played some

  为了更好地了解构效关系，合成了取代的 4-杂芳基-2-苯基喹啉并在 NK-2 和 NK-3 受体上进行了测试。总的来说，这些可被视为 NK-3 拮抗剂 SB 218795 的生物电子等排体的分子显示出比模板低的活性。环电子分布和H-键供体和受体位置在选择性中起一定作用，2-咪唑基取代的2a主要对NK-3表现出亲和力，而3-吡唑基取代的4表现出与NK-2受体的优先相互作用。合成化合物的结构表征是通过核磁共振和质谱技术实现的。二维 1H-NOESY 实验是确定化合物 9 和 11b – c 的异构结构的有用工具。