4-[(2-fluoro-3-methoxy-6-methoxymethoxy-phenyl)-hydroxy-methyl]-benzoicacidmethylester | 677323-83-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 4-[(2-fluoro-3-methoxy-6-methoxymethoxy-phenyl)-hydroxy-methyl]-benzoicacidmethylester
• 英文别名: 4-[(2-fluoro-3-methoxy-6-methoxymethoxyphenyl)hydroxymethyl]benzoic acid methyl ester；4-[(2-fluoro-3-methoxy-6-methoxymethoxy-phenyl)-hydroxy-methyl]-benzoic acid methyl ester；Methyl 4-[[2-fluoro-3-methoxy-6-(methoxymethoxy)phenyl]-hydroxymethyl]benzoate
• CAS: 677323-83-0
• 化学式: C₁₈H₁₉FO₆
• 分子量: 350.344
• InChiKey: ABCWSJMBSGOZGZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  25
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  74.2
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  4-[(2-fluoro-3-methoxy-6-methoxymethoxy-phenyl)-hydroxy-methyl]-benzoicacidmethylester 在 manganese(IV) oxide 作用下， 以 二氯甲烷 为溶剂， 以86%的产率得到4-(2-fluoro-6-hydroxymethoxy-3-methoxy-benzoyl)-benzoic acid methyl ester
  参考文献：
  名称：

  [EN] LABELED PKG-1-ALPHA-BINDING COMPOUNDS AND THEIR USE IN IMAGING AND QUANTIFYING PAIN
  [FR] COMPOSÉS MARQUÉS DE LIAISON À LA PKG-1-ALPHA ET LEUR UTILISATION POUR PRENDRE DES IMAGES ET QUANTIFIER LA DOULEUR

  摘要：

  本发明涉及使用选择性结合到激活的蛋白激酶G1α的化合物来成像慢性疼痛的解剖基础。这种成像也可用于客观量化慢性疼痛。具体地，本发明揭示了氟-18和碳-11标记的NOP化合物，[18F] NOP46 和 [11C]NOP46，用作成像剂来检测和量化神经病性疼痛。

  公开号：

  WO2014210167A1
• 作为产物：
  描述：

  2-氟苯甲醚 在 aluminum (III) chloride 、 正丁基锂 、 N,N-二异丙基乙胺 、 间氯过氧苯甲酸 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 90.0h， 生成 4-[(2-fluoro-3-methoxy-6-methoxymethoxy-phenyl)-hydroxy-methyl]-benzoicacidmethylester
  参考文献：
  名称：

  WO2006/136829

  摘要：

  公开号：

文献信息

• Neuronal Pain Pathway Modulators
  申请人：Ambron Richard

  公开号：US20080176920A1

  公开（公告）日：2008-07-24

  The present invention relates to compounds that may be used to inhibit activation of protein kinase G (“PKG”). It is based, at least in part, on the discovery of the tertiary structure of PKG and the identification of molecules that either bind to the active site of PKG and/or are analogs of balanol.

  本发明涉及可用于抑制蛋白激酶G（PKG）激活的化合物。至少部分基于对PKG的三级结构的发现以及发现绑定于PKG活性位点和/或是巴洛酮类似物的分子的识别。
• NEURONAL PAIN PATHWAY MODULATORS
  申请人：The Trustees of Columbia University in the City of New York

  公开号：US20150126576A1

  公开（公告）日：2015-05-07

  The present invention relates to compounds that may be used to inhibit activation of protein kinase G (“PKG”). It is based, at least in part, on the discovery of the tertiary structure of PKG and the identification of molecules that either bind to the active site of PKG and/or are analogs of balanol.

  本发明涉及可用于抑制蛋白激酶G（“PKG”）激活的化合物。它至少部分地基于发现PK G的三级结构以及识别既能够与PKG的活性位点结合，又是巴洛诺（balanol）的类似物的分子。
• Labeled pkg-1-alpha-binding compounds and their use in imaging and quantifying pain
  申请人：THE TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK

  公开号：US10098975B2

  公开（公告）日：2018-10-16

  The present invention relates to the use of compounds that selectively bind to activated protein kinase G 1 alpha for imaging the anatomic basis for chronic pain. Such imaging may also be used to objectively quantify chronic pain.

  本发明涉及使用选择性结合活化蛋白激酶 G 1 alpha 的化合物对慢性疼痛的解剖基础进行成像。这种成像还可用于客观量化慢性疼痛。
• Structure-Based Optimization of Novel Azepane Derivatives as PKB Inhibitors
  作者：Christine B. Breitenlechner、Thomas Wegge、Laurent Berillon、Klaus Graul、Klaus Marzenell、Walter-Gunar Friebe、Ulrike Thomas、Ralf Schumacher、Robert Huber、Richard A. Engh、Birgit Masjost

  DOI：10.1021/jm0310479

  日期：2004.3.1

  Novel azepane derivatives were prepared and evaluated for protein kinase B (PKB-alpha) and protein kinase A (PKA) inhibition. The original (-)-balanol-derived lead structure (4R)-4-(2fluoro-6-hydroxy-3-methoxy-benzoyl)-benzoic acid (3R)-3-[(pyridine-4-carbonyl)aminol-azepan4-yl ester (1) (IC50 (PKB-alpha.) = 5 nM) which contains an ester moiety was found to be plasma unstable and therefore unsuitable as a drug. Based upon molecular modeling studies using the crystal structure of the complex between PKA and 1, the five compounds N-(3R,4R)-4-[4-(2-fluoro-6-hydroxy-3-methoxy-benzoyl)-benzoylamino]-azepan-3-yl}-isonicotinamide (4), (3R,4R)-N-4-[4-(2-fluoro-6-hydroxy-3-methoxy-benzoyl)-benzyloxy]-azepan-3-yl}-isonicotinamide (5), N-(3R,4S)-4-[4-(2-fluoro-6-hydroxy-3-methoxy-benzoyl)-phenylamino]-methyl}-azepan-3-yl)-isonicotinamide (6), N-(3R,4R)-4-[4-(2-fluoro-6-hydroxy-3-methoxy-benzoyl)-benzylamino]-azepan-3-yl}-isonicotinamide (7), and N-(3R,4S)-4-(4-trans-2-[4-(2-fluoro-6-hydroxy-3-methoxy-benzoyl)-phenyl] -vinyl}-azepan-3-yl)-isonicotinamide (8) with linkers isosteric to the ester were designed, synthesized, and tested for in vitro inhibitory activity against PKA and PKB-alpha and for plasma stability in mouse plasma.(1)Compound 4 was found to be plasma stable and highly active (IC50 (PKB-alpha) = 4 nM). Cocrystals with PKA were obtained for 4, 5, and 8 and analyzed for binding interactions and conformational changes in the ligands and protein in order to rationalize the different activities of the molecules.
• PYRAZOLE DERIVATIVES AND THEIR USE AS PKA AND PKB MODULATORS
  申请人：Astex Therapeutics Limited

  公开号：EP1919875A2

  公开（公告）日：2008-05-14