5-(2-Bromo-5-methoxy-phenyl)-3-oxo-pentanoic acid methyl ester | 909190-82-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 5-(2-Bromo-5-methoxy-phenyl)-3-oxo-pentanoic acid methyl ester
• 英文别名: Methyl 5-(2-bromo-5-methoxyphenyl)-3-oxopentanoate
• CAS: 909190-82-5
• 化学式: C₁₃H₁₅BrO₄
• 分子量: 315.164
• InChiKey: JYAGWAZQGYQTME-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  18
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  52.6
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  5-(2-Bromo-5-methoxy-phenyl)-3-oxo-pentanoic acid methyl ester 在 copper(l) iodide 、 caesium carbonate 作用下， 以 1,4-二氧六环 为溶剂， 反应 20.0h， 以67%的产率得到1-carbomethoxy-6-methoxy-2-tetralone
  参考文献：
  名称：

  O-Arylation versus C-Arylation:  Copper-Catalyzed Intramolecular Coupling of Aryl Bromides with 1,3-Dicarbonyls

  摘要：

  The copper-catalyzed intramolecular coupling of aryl bromides with 1,3-dicarbonyls via a six-membered ring closure was examined. With CuI (10 mol %) as the catalyst, N,N'-dimethylethylenediamine as the ligand, and Cs2CO3 as the base, the reactions of alpha-(2-bromobenzyl)-beta-keto esters in THF at refluxing temperature afforded the corresponding substituted 4H-1-benzopyrans in high yields via O-arylation. On the other hand, the reactions of delta-(2-bromophenyl)-beta-keto esters in refluxing dioxane led to the formation of 3,4-dihydronaphthalen-2(1H)-one derivatives via C-arylation.

  DOI：

  10.1021/jo060747t
• 作为产物：
  描述：

  methyl acetoacetate 、 2-溴-5-甲氧基溴苄 在 正丁基锂 、 二异丙胺 、 四甲基乙二胺 作用下， 以 四氢呋喃 、 正己烷 为溶剂， 反应 1.0h， 生成 5-(2-Bromo-5-methoxy-phenyl)-3-oxo-pentanoic acid methyl ester
  参考文献：
  名称：

  [EN] NIACIN RECEPTOR AGONISTS, COMPOSITIONS CONTAINING SUCH COMPOUNDS AND METHODS OF TREATMENT
  [FR] AGONISTES DES RECEPTEURS DE NIACINE, COMPOSITIONS CONTENANT LESDITS COMPOSES ET METHODES DE TRAITEMENT

  摘要：

  公开号：

  WO2006052555A3

文献信息

• Niacin Receptor Agonists, Compositions Containing Such Compounds and Methods of Treatment
  申请人：Imbriglio Jason

  公开号：US20090042926A1

  公开（公告）日：2009-02-12

  The present invention encompasses compounds of Formula (I): as well as pharmaceutically acceptable salts and hydrates thereof, that are useful for treating atherosclerosis, dyslipidemias and the like. Pharmaceutical compositions and methods of use are also included.

  本发明涵盖以下式（I）的化合物：以及其药学上可接受的盐和水合物，其对于治疗动脉粥样硬化、血脂异常等具有用处。还包括药物组合物和使用方法。
• The discovery of high affinity agonists of GPR109a with reduced serum shift and improved ADME properties
  作者：Jason E. Imbriglio、Daniel DiRocco、Rena Bodner、Subharekha Raghavan、Weichun Chen、Daria Marley、Craig Esser、Tom G. Holt、Michael S. Wolff、Andrew K.P. Taggart、M. Gerard Waters、James R. Tata、Steven L. Colletti

  DOI：10.1016/j.bmcl.2010.11.116

  日期：2011.5

  Amino-anthranilic acid derivatives have been identified as a new class of low serum shifted, high affinity full agonists of the human orphan G-protein-coupled receptor GPR109a with improved ADME properties. (C) 2010 Elsevier Ltd. All rights reserved.
• Discovery of Novel Tricyclic Full Agonists for the G-Protein-Coupled Niacin Receptor 109A with Minimized Flushing in Rats
  作者：Hong C. Shen、Fa-Xiang Ding、Qiaolin Deng、Larissa C. Wilsie、Mihajlo L. Krsmanovic、Andrew K. Taggart、Ester Carballo-Jane、Ning Ren、Tian-Quan Cai、Tsuei-Ju Wu、Kenneth K. Wu、Kang Cheng、Qing Chen、Michael S. Wolff、Xinchun Tong、Tom G. Holt、M. Gerard Waters、Milton L. Hammond、James R. Tata、Steven L. Colletti

  DOI：10.1021/jm900151e

  日期：2009.4.23

  Tricyclic analogues were rationally designed as the high affinity niacin receptor G-protein-coupled receptor 109A (GPR109A) agonists by overlapping three lead structures. Various tricyclic anthranilide and cycloalkene carboxylic acid full agonists were discovered with excellent in vitro activity. Compound 2g displayed a good therapeutic index regarding free fatty acids (FFA) reduction and vasodilation effects in rats, with very weak cytochrome P450 2C8 (CYP2C8) and cytochrome P450 2C9 (CYP2C9) inhibition, and a good mouse pharmacokinetics (PK) profile.
• [EN] NIACIN RECEPTOR AGONISTS, COMPOSITIONS CONTAINING SUCH COMPOUNDS AND METHODS OF TREATMENT<br/>[FR] AGONISTES DES RECEPTEURS DE NIACINE, COMPOSITIONS CONTENANT LESDITS COMPOSES ET METHODES DE TRAITEMENT
  申请人：MERCK & CO INC

  公开号：WO2006052555A3

  公开（公告）日：2006-06-22
• O-Arylation versus C-Arylation:  Copper-Catalyzed Intramolecular Coupling of Aryl Bromides with 1,3-Dicarbonyls
  作者：Yewen Fang、Chaozhong Li

  DOI：10.1021/jo060747t

  日期：2006.8.1

  The copper-catalyzed intramolecular coupling of aryl bromides with 1,3-dicarbonyls via a six-membered ring closure was examined. With CuI (10 mol %) as the catalyst, N,N'-dimethylethylenediamine as the ligand, and Cs2CO3 as the base, the reactions of alpha-(2-bromobenzyl)-beta-keto esters in THF at refluxing temperature afforded the corresponding substituted 4H-1-benzopyrans in high yields via O-arylation. On the other hand, the reactions of delta-(2-bromophenyl)-beta-keto esters in refluxing dioxane led to the formation of 3,4-dihydronaphthalen-2(1H)-one derivatives via C-arylation.