6-bromo-4-methylcoumarin-3-carboxylic acid | 773109-55-0

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 香豆素及其衍生物
• 英文名称: 6-bromo-4-methylcoumarin-3-carboxylic acid
• 英文别名: UBP714；6-bromo-4-methyl-2-oxo-2H-chromene-3-carboxylic acid；6-bromo-4-methyl-2-oxochromene-3-carboxylic acid
• CAS: 773109-55-0
• 化学式: C₁₁H₇BrO₄
• mdl: MFCD06208402
• 分子量: 283.078
• InChiKey: BWBWVUJRXNIUMA-UHFFFAOYSA-N

物化性质

• 沸点：
  436.8±45.0 °C(Predicted)
• 密度：
  1.752±0.06 g/cm3(Predicted)
• 溶解度：
  DMSO：可溶15mg/mL，澄清

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  16
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  63.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  6-bromo-4-methylcoumarin-3-carboxylic acid 在 4-二甲氨基吡啶 、 tris-(dibenzylideneacetone)dipalladium(0) 、 N,N'-二环己基碳二亚胺 、 4,5-双二苯基膦-9,9-二甲基氧杂蒽 作用下， 以 二氯甲烷 、 甲苯 为溶剂， 反应 12.0h， 生成 6-bromo-4-(but-3-en-1-yl)-2H-chromen-2-one
  参考文献：
  名称：

  香豆素的迁移脱羧偶联：合成和机理方面

  摘要：

  进展：烯丙基 4-甲基-3-羧基香豆素的脱羧偶联提供了甲基 γ-烯丙基化的产物，而不是典型的区域特异性 α-烯丙基化。机理研究表明，分子内质子从 4-甲基转移到 3-羧酸酯可以实现远程甲基的烯丙基化。所得的 4-丁烯基-3-羧基香豆素经过 Pd 0催化脱羧，得到观察到的产物（参见方案）。

  DOI：

  10.1002/anie.201100765
• 作为产物：
  描述：

  2-羟基-5-溴苯乙酮 在 硫酸 、 sodium ethanolate 、 sodium hydroxide 作用下， 以 乙醇 、 水 为溶剂， 反应 3.0h， 生成 6-bromo-4-methylcoumarin-3-carboxylic acid
  参考文献：
  名称：

  香豆素的迁移脱羧偶联：合成和机理方面

  摘要：

  进展：烯丙基 4-甲基-3-羧基香豆素的脱羧偶联提供了甲基 γ-烯丙基化的产物，而不是典型的区域特异性 α-烯丙基化。机理研究表明，分子内质子从 4-甲基转移到 3-羧酸酯可以实现远程甲基的烯丙基化。所得的 4-丁烯基-3-羧基香豆素经过 Pd 0催化脱羧，得到观察到的产物（参见方案）。

  DOI：

  10.1002/anie.201100765

文献信息

• Coumarin-3-carboxylic acid derivatives as potentiators and inhibitors of recombinant and native N-methyl-d-aspartate receptors
  作者：Mark W. Irvine、Blaise M. Costa、Arturas Volianskis、Guangyu Fang、Laura Ceolin、Graham L. Collingridge、Daniel T. Monaghan、David E. Jane

  DOI：10.1016/j.neuint.2011.12.020

  日期：2012.9

  N-Methyl-D-aspartate receptors (NMDARs) are known to be involved in a range of neurological and neurodegenerative disorders and consequently the development of compounds that modulate the function of these receptors has been the subject of intense interest. We have recently reported that 6-bromocoumarin-3-carboxylic acid (UBP608) is a negative allosteric modulator with weak selectivity for GluN2A-containing NMDARs. In the present study, a series of commercially available and newly synthesized coumarin derivatives have been evaluated in a structure-activity relationship (SAR) study as modulators of recombinant NMDAR activity. The main conclusions from this SAR study were that substituents as large as iodo were accommodated at the 6-position and that 6,8-dibromo or 6,8-diiodo substitution of the coumarin ring enhanced the inhibitory activity at NMDARs. These coumarin derivatives are therefore excellent starting points for the development of more potent and GluN2 subunit selective inhibitors, which may have application in the treatment of a range of neurological disorders such as neuropathic pain, epilepsy and depression. Surprisingly, 4-methyl substitution of UBP608 to give UBP714, led to conversion of the inhibitory activity of UBP608 into potentiating activity at recombinant GluN1/GluN2 receptors. UBP714 also enhanced NMDAR mediated field EPSPs in the CA1 region of the hippocampus. UBP714 is therefore a novel template for the development of potent and subunit selective NMDAR potentiators that may have therapeutic applicability in the treatment of patients with cognitive deficits or schizophrenia. (C) 2012 Elsevier Ltd. All rights reserved.
• NEUROACTIVE COMPOUNDS AND METHODS OF USE THEREOF
  申请人：Sage Therapeutics, Inc.

  公开号：US20170304321A1

  公开（公告）日：2017-10-26

  Methods for treating a subject suffering from a sterol synthesis disorder or a sterol deficiency disorder, e.g., Smith-Lemli-Opitz syndrome, the method comprising administering to the subject an effective amount of an NMDA receptor modulating compound, are provided.
• [EN] BIOMIMETIC CHELATING AGENTS AND METHODS<br/>[FR] AGENTS ET METHODES DE CHELATION BIOMIMETIQUE
  申请人：SYNCHEM RESERACH INC

  公开号：WO2000021941A1

  公开（公告）日：2000-04-20

  A method of controlling systemic copper levels in mammals includes administering to a mammal a compound which is preferentially bound by hepatocytes, serum albumin, or both, and which selectively binds with copper. The compounds can be administered to patients by oral or intravenous or topical routes in a phamaceutically acceptable vehicle, at a dosage which is dependent on the composition of the selected compound on the copper level, body weight of the patient or upon the surface area of skin being treated. The compounds of this invention have particular utility in the treatment of Wilson's Disease, angiogenic forms of cancer, psoriasis, and other pathologies in which angiogenesis causes or exacerbates the disease.
• [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.
• [EN] NEUROACTIVE COMPOUNDS AND METHODS OF USE THEREOF<br/>[FR] COMPOSÉS NEUROACTIFS ET LEURS PROCÉDÉS D'UTILISATION
  申请人：SAGE THERAPEUTICS INC

  公开号：WO2016057713A1

  公开（公告）日：2016-04-14

  Methods for treating a subject suffering from a sterol synthesis disorder or a sterol deficiency disorder, e.g., Smith-Lemli-Opitz syndrome, the method comprising administering to the subject an effective amount of an NMDA receptor modulating compound, are provided.