9-bromophenanthrene-3-carboxylic acid

• 分子结构分类: 有机化合物 - 苯类化合物 - 菲及其衍生物
• 英文名称: 9-bromophenanthrene-3-carboxylic acid
• 英文别名: 9-bromo-phenanthrene-3-carboxylic acid；9-Brom-phenanthren-3-carbonsaeure
• 化学式: C₁₅H₉BrO₂
• 分子量: 301.139
• InChiKey: RPCWJIQXDDOMKY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.2
• 重原子数：
  18
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  37.3
• 氢给体数：
  1
• 氢受体数：
  2

上下游信息

• 上游原料

  中文名称	英文名称	CAS号	化学式	分子量
  1-(9-溴菲-3-基)乙酮	3-Acetyl-9-brom-phenanthren	6328-08-1	C16H11BrO	299.167
  9-溴菲	9-bromophenanthrene	573-17-1	C14H9Br	257.129

• 下游产品

  中文名称	英文名称	CAS号	化学式	分子量
  ——	methyl 9-formylphenanthrene-3-carboxylate	1357838-21-1	C17H12O3	264.28
  ——	methyl 9-vinylphenanthrene-3-carboxylate	——	C18H14O2	262.308
  ——	9-(4-methylpent-1-yl)phenanthrene-3-carboxylic acid	1333213-35-6	C21H22O2	306.404
  ——	9-cyclopropylphenanthrene-3-carboxylic acid	1333111-40-2	C18H14O2	262.308

反应信息

• 作为反应物：
  描述：

  9-bromophenanthrene-3-carboxylic acid 在 palladium diacetate 、 三(邻甲基苯基)磷 四氧化锇 、 水 、 potassium carbonate 、 三乙胺 作用下， 以 N,N-二甲基甲酰胺 、 叔丁醇 为溶剂， 反应 84.0h， 生成 methyl 9-formylphenanthrene-3-carboxylate
  参考文献：
  名称：

  [EN] COMPOUNDS FOR USE IN MODULATING THE NMDA RECEPTOR
  [FR] MODULATEURS POSITIFS ET NÉGATIFS DES RÉCEPTEURS NMDA

  摘要：

  公开号：

  WO2012019106A8
• 作为产物：
  描述：

  9-溴菲 在 aluminum (III) chloride 、 溴 、 sodium hydroxide 作用下， 以 1,4-二氧六环 为溶剂， 反应 1.0h， 生成 9-bromophenanthrene-3-carboxylic acid
  参考文献：
  名称：

  Piperazine-2,3-dicarboxylic Acid Derivatives as Dual Antagonists of NMDA and GluK1-Containing Kainate Receptors

  摘要：

  Competitive N-methyl-D-aspartate receptor (NMDAR) antagonists bind to the GluN2 subunit, of which there are four types (GluN2A-D). We report that some N-1-substituted derivatives of cis-piperazine-2,3-dicarboxylic acid display improved relative affinity for GluN2C and GluN2D versus GluN2A and GluN2B. These derivatives also display subtype selectivity among the more distantly related kainate receptor family. Compounds 18i and (-)-4 were the most potent kainate receptor antagonists, and 18i was selective for GluK1 versus GluK2, GluK3 and AMPA receptors. Modeling studies revealed structural features required for activity at GluK1 subunits and suggested that S674 was vital for antagonist activity. Consistent with this hypothesis, replacing the equivalent residue in GluK3 (alanine) with a serine imparts 18i antagonist activity. Antagonists with dual GluN2D and GluK1 antagonist activity may have beneficial effects in various neurological disorders. Consistent with this idea, antagonist 18i (30 mg/kg ip) showed antinociceptive effects in an animal model of mild nerve injury.

  DOI：

  10.1021/jm201230z

文献信息

• Synthesis of a Series of Novel 3,9-Disubstituted Phenanthrenes as Analogues of Known N-Methyl-d-aspartate Receptor Allosteric Modulators
  作者：Mark Irvine、Guangyu Fang、Richard Eaves、Maria Mayo-Martin、Erica Burnell、Blaise Costa、Georgia Culley、Arturas Volianskis、Graham Collingridge、Daniel Monaghan、David Jane

  DOI：10.1055/s-0034-1380114

  日期：2015.6

  9-Substituted phenanthrene-3-carboxylic acids have been reported to have allosteric modulatory activity at the N-methyl-d-aspartate (NMDA) receptor. This receptor is activated by the excitatory neurotransmitter l-glutamate and has been implicated in a range of neurological disorders such as schizophrenia, epilepsy and chronic pain, and in neurodegenerative disorders such as Alzheimer’s disease. Herein, the convenient synthesis of a wide range of novel 3,9-disubstituted phenanthrene derivatives starting from a few common intermediates is described. These new phenanthrene derivatives will help to clarify the structural requirements for allosteric modulation of the NMDA receptor.

  9-取代菲3-羧酸据报道具有对N-甲基-d-天冬氨酸（NMDA）受体的变构调节活性。该受体被兴奋性神经递质l-谷氨酸激活，并已被认为与一系列神经系统疾病（如精神分裂症、癫痫和慢性疼痛）以及神经退行性疾病（如阿尔茨海默病）有关。本文描述了从几种常见中间体出发合成一系列新型3,9-二取代菲衍生物的便捷方法。这些新的菲衍生物将有助于阐明对NMDA受体的变构调节的结构要求。
• ATTEMPTS TO FIND NEW ANTIMALARIALS. XII. DERIVATIVES OF PHENANTHRENE, IV. 1 (OR 8)-ACETYL-9-HALOPHENANTHRENE
  作者：J. SCHULTZ、M. A. GOLDBERG、E. P. ORDAS、G. CARSCH

  DOI：10.1021/jo01174a004

  日期：1946.7
• STUDIES IN THE PHENANTHRENE SERIES. II. PHENANTHRENE CARBOXYLIC ACIDS AND 9-BROMOPHENANTHRENE DERIVATIVES¹
  作者：Erich Mosettig、Jacob van de Kamp

  DOI：10.1021/ja01347a046

  日期：1932.8
• [EN] POSITIVE AND NEGATIVE MODULATORS OF NMDA RECEPTORS<br/>[FR] MODULATEURS POSITIFS ET NÉGATIFS DES RÉCEPTEURS NMDA
  申请人：UNIV NEBRASKA

  公开号：WO2012019106A2

  公开（公告）日：2012-02-09

  Disclosed herein are compounds useful as modulators of an NMDA receptor. Further disclosed are methods of modulating an NMDA receptor using these compounds, and methods of treating various NMDA-receptor disorders, such as, for example, schizophrenia, post-traumatic stress disorder, Alzheimer's disease, and pain.
• Piperazine-2,3-dicarboxylic Acid Derivatives as Dual Antagonists of NMDA and GluK1-Containing Kainate Receptors
  作者：Mark W. Irvine、Blaise M. Costa、Daniel Dlaboga、Georgia R. Culley、Richard Hulse、Caroline L. Scholefield、Palmi Atlason、Guangyu Fang、Richard Eaves、Richard Morley、Maria B. Mayo-Martin、Mascia Amici、Zuner A. Bortolotto、Lucy Donaldson、Graham L. Collingridge、Elek Molnár、Daniel T. Monaghan、David E. Jane

  DOI：10.1021/jm201230z

  日期：2012.1.12

  Competitive N-methyl-D-aspartate receptor (NMDAR) antagonists bind to the GluN2 subunit, of which there are four types (GluN2A-D). We report that some N-1-substituted derivatives of cis-piperazine-2,3-dicarboxylic acid display improved relative affinity for GluN2C and GluN2D versus GluN2A and GluN2B. These derivatives also display subtype selectivity among the more distantly related kainate receptor family. Compounds 18i and (-)-4 were the most potent kainate receptor antagonists, and 18i was selective for GluK1 versus GluK2, GluK3 and AMPA receptors. Modeling studies revealed structural features required for activity at GluK1 subunits and suggested that S674 was vital for antagonist activity. Consistent with this hypothesis, replacing the equivalent residue in GluK3 (alanine) with a serine imparts 18i antagonist activity. Antagonists with dual GluN2D and GluK1 antagonist activity may have beneficial effects in various neurological disorders. Consistent with this idea, antagonist 18i (30 mg/kg ip) showed antinociceptive effects in an animal model of mild nerve injury.