4-二甲基氨基甲基-6-氟-2-甲氧基苯酚 | 103905-49-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 酚类
• 中文名称: 4-二甲基氨基甲基-6-氟-2-甲氧基苯酚
• 英文名称: N,N-dimethyl-3-hydroxy-4-methoxy-5-fluorobenzylamine
• 英文别名: 4-(Dimethylaminomethyl)-6-fluoro-2-methoxyphenol；4-[(dimethylamino)methyl]-2-fluoro-6-methoxyphenol
• CAS: 103905-49-3
• 化学式: C₁₀H₁₄FNO₂
• mdl: MFCD04972107
• 分子量: 199.225
• InChiKey: NOTMCGGOLLFMRG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  14
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  32.7
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-二甲基氨基甲基-6-氟-2-甲氧基苯酚 在 盐酸 、 乌洛托品 、 ammonium acetate 、 四丁基硫酸氢铵 、 溶剂黄146 、 sodium hydroxide 、 锌 作用下， 以 甲醇 、 二氯甲烷 、 氯仿 、 水 、 溶剂黄146 为溶剂， 反应 13.5h， 生成 3,4-dimethoxy-5-fluorophenethylamine
  参考文献：
  名称：

  Chemoselective Zinc/HCl Reduction of Halogenated β-Nitrostyrenes: Synthesis of Halogenated Dopamine Analogues

  摘要：

  A detailed account regarding the synthesis of 2- and 5-halogenated dopamine is given. The key step is a chemoselective reduction of a nitrostyrene by Zn/HCl at 0 degrees C. These conditions represent a simple, low-cost alternative to reduction by water-sensitive hydride donors and two-step procedures. Under these conditions, aryl fluoride, chloride, and bromide groups are stable. However, iodine undergoes significant reductive dehalogenation.

  DOI：

  10.1055/s-0034-1379481
• 作为产物：
  描述：

  间氟苯甲醚 以 乙醇 、 水 为溶剂， 反应 42.0h， 生成 4-二甲基氨基甲基-6-氟-2-甲氧基苯酚
  参考文献：
  名称：

  4-氟，7-氟和4,7-二氟-5,6-二羟基色胺的合成和生物学评估。

  摘要：

  合成了5,6-二羟基色胺（5,6-DHT）衍生物4-氟-和7-氟-5,6-DHT（26a，b）和4,7-二氟-5,6-DHT（26c）分别由3-氟茴香醚（1）和1,4-二氟-2,3-二甲氧基苯（13）制成。已开发出有效的方法，用于将1转化为4-氟-和7-氟-5,6-双（苄氧基）吲哚（分别为12a，b）和从13转化为4,7-二氟-5,6- [ （二苯基亚甲基）二氧基]吲哚（19）是由2-硝基甲苯就地制备的2-硝基-β-（二烷基氨基）苯乙烯的还原环化反应。然后通过相应的吲哚-3-乙腈将吲哚12a，b和19转化为26a-c。用分光光度法测定，氟取代的5,6-DHTs显示出增加的苯酚酸度，并且通过循环伏安法测定，其发生氧化的固有电势降低。从抑制26a，c和5，6-DHT的IC50值分别得出117、125、135和92 microM的IC50值判断，氟取代对细胞毒性潜能没有明显的不利影响，从而抑制了

  DOI：

  10.1021/jm00170a026

文献信息

• [EN] cGAS ANTAGONIST COMPOUNDS<br/>[FR] COMPOSÉS ANTAGONISTES DU CGAS
  申请人：IMMUNE SENSOR LLC

  公开号：WO2017176812A1

  公开（公告）日：2017-10-12

  Disclosed are novel compounds of Formula (I) that are cGAS antagonists, methods of preparation of the compounds, pharmaceutical compositions comprising the compounds, and their use in medical therapy.

  揭示了一种新型化合物的化学式（I），这些化合物是cGAS拮抗剂，涉及到这些化合物的制备方法、包含这些化合物的药物组合物，以及它们在医学治疗中的应用。
• Fragment-Based Discovery of Novel Potent Sepiapterin Reductase Inhibitors
  作者：Jo Alen、Markus Schade、Markus Wagener、Frank Christian、Sonja Nordhoff、Beatrix Merla、Torsten R. Dunkern、Gregor Bahrenberg、Paul Ratcliffe

  DOI：10.1021/acs.jmedchem.9b00218

  日期：2019.7.11

  Here we used 19F NMR fragment screening for the discovery of novel, ligand-efficient SPR inhibitors. We report the crystal structures of six chemically diverse inhibitors complexed with SPR, identifying relevant interactions and binding modes in the sepiapterin pocket. Exploration of our initial fragment screening hit led to double-digit nanomolar inhibitors of SPR with excellent ligand efficiency.

  在慢性下背痛患者中的全基因组关联研究认为，Sepaapterin还原酶是开发新型镇痛药的重要目标。在这里，我们使用19 F NMR片段筛选来发现新型的，配体有效的SPR抑制剂。我们报告了与SPR配合使用的六种化学多样的抑制剂的晶体结构，确定了Sepaapterin口袋中的相关相互作用和结合模式。对我们最初的片段筛选命中的探索导致了具有出色配体效率的两位数纳摩尔SPR抑制剂。
• Synthesis and biological evaluation of 4-fluoro-, 7-fluoro-, and 4,7-difluoro-5,6-dihydroxytryptamines
  作者：Masami Kawase、Achintya K. Sinhababu、Eva M. McGhee、Terry Milby、Ronald T. Borchardt

  DOI：10.1021/jm00170a026

  日期：1990.8

  synthesized from 3-fluoroanisole (1) and 1,4-difluoro-2,3-dimethoxybenzene (13), respectively. Efficient methods were developed for the conversion of 1 to 4-fluoro- and 7-fluoro-5,6-bis(benzyloxy)indoles (12a,b, respectively), and 13 to 4,7-difluoro-5,6-[( diphenylmethylene)dioxy]indole (19) via reductive cyclization of 2-nitro-beta-(dialkylamino)styrenes prepared in situ from 2-nitrotoluenes. Indoles 12a

  合成了5,6-二羟基色胺（5,6-DHT）衍生物4-氟-和7-氟-5,6-DHT（26a，b）和4,7-二氟-5,6-DHT（26c）分别由3-氟茴香醚（1）和1,4-二氟-2,3-二甲氧基苯（13）制成。已开发出有效的方法，用于将1转化为4-氟-和7-氟-5,6-双（苄氧基）吲哚（分别为12a，b）和从13转化为4,7-二氟-5,6- [ （二苯基亚甲基）二氧基]吲哚（19）是由2-硝基甲苯就地制备的2-硝基-β-（二烷基氨基）苯乙烯的还原环化反应。然后通过相应的吲哚-3-乙腈将吲哚12a，b和19转化为26a-c。用分光光度法测定，氟取代的5,6-DHTs显示出增加的苯酚酸度，并且通过循环伏安法测定，其发生氧化的固有电势降低。从抑制26a，c和5，6-DHT的IC50值分别得出117、125、135和92 microM的IC50值判断，氟取代对细胞毒性潜能没有明显的不利影响，从而抑制了
• 5-fluoro-and 8-fluoro-trimetoquinol compounds and the processes for
  申请人：Ohio State University Research Foundation

  公开号：US04737504A1

  公开（公告）日：1988-04-12

  The present invention relates to novel 5-fluoro- and 8-fluoro-trimetoquinol compounds of the general formula I wherein X.sub.1 =F,X.sub.2 =H or X.sub.1 =H,X.sub.2 =F ##STR1## The present invention also relates to a process for making the 5-fluoro- and 8-fluoro-trimetoquinol compounds by condensation of an appropriately substituted phenethylamine to afford an appropriately substituted phenethylacetamide compound. The amides are cyclized to give appropriately substituted intermediate dihydroisoquinolines. Without isolation, the dihydroisoquinolines are reduced to give appropriately substituted tetrahydroisoqinolines. The hydrochloride salts of tetrahydroisoqinolines are prepared and subjected to hydrogenolysis, to give the fluorine substituted trimetoquinol compounds of the present invention. The present invention also encompasses the preparation of the phenethylamines by reducing appropriately substituted benzylcyanides and to the preparation of an intermediate benzylcyanide compound by converting a fluorine substituted methoxyphenol compound, under aminomethylation conditions into a N, N-dimethyl-4-hydroxy-3-methoxy-5-fluorobenzylamine. The benzylamine is converted to benzylnitrile and a functional group shuffle is carried out which yields the appropriately substituted benzylcyanide compound. In a composition aspect, the present invention encompasses novel pharmaceutical compositions comprising a compound of the formula I, together with a physiologically acceptable carrier or excipient, in an amount sufficient to increase .beta..sub.2 -adrenergic and antithrombotic activities while simultaneously decreasing the .beta..sub.1 -adrenergic activity in mammals, including humans. The compounds of the invention are useful in the treatment of pulmonary, cardiovascular or thromboembolic disorders.

  本发明涉及一种新的5-氟和8-氟三甲氧喹酮化合物，其通式为I，其中X.sub.1 =F，X.sub.2 =H或X.sub.1 =H，X.sub.2 =F。本发明还涉及一种制备5-氟和8-氟三甲氧喹酮化合物的方法，通过将适当取代的苯乙胺缩合以得到适当取代的苯乙酰胺化合物。酰胺环化得到适当取代的中间二氢异喹啉。在没有分离的情况下，将二氢异喹啉还原得到适当取代的四氢异喹啉。四氢异喹啉的盐酸盐被制备并经氢解，得到本发明的氟取代三甲氧喹酮化合物。本发明还涵盖了通过还原适当取代的苄基氰化物制备苯乙胺，以及通过将氟取代的甲氧基苯酚化合物在氨甲基化条件下转化为N，N-二甲基-4-羟基-3-甲氧基-5-氟苄胺制备中间苄基氰化合物。苄胺转化为苯乙腈，并进行功能基转移，得到适当取代的苄基氰化合物。在组合方面，本发明涵盖了包含通式I化合物的新型药物组合物，与生理上可接受的载体或赋形剂一起使用，用量足以增加哺乳动物，包括人类的β2-肾上腺素能和抗血栓活性，同时减少β1-肾上腺素能活性。本发明的化合物在治疗肺部、心血管或血栓性疾病中有用。
• 5-fluoro- and 8-fluoro-trimetoquinol compounds and the processes for
  申请人：Ohio State University Research Foundation

  公开号：US04855476A1

  公开（公告）日：1989-08-08

  The present invention relates to novel 5-fluoro- and 8-fluoro-trimetoquinol compounds of the general formula I wherein X.sub.1 =F, X.sub.2 =H or X.sub.1 =H, X.sub.2 =F ##STR1## The present invention also relates to a process for making the 5-fluoro- and 8-fluoro-trimetoquinol compounds by condensation of an appropriately substituted phenethylamine to afford an appropriately substituted phenlethylacetamide compound. The amides are cyclized to give appropriately substituted intermediate dihydroisoquinolines. Without isolation, the dihydroisoquinolines are reduced to give appropriately substituted tetrahydroisoquinolines. The hydrochloride salts of tetrahydroisoquinolines are prepared and subjected to hydrogenolysis, to give the fluorine substituted trimetoquinol compounds of the present invention. The present invention also encompasses the preparation of the phenethylamines by reducing appropriately substituted benzylcyanides and to the preparation of an intermediate benzylcyanide compound by converting a fluorine substituted methoxyphenol compound, under aminomethylation conditions into a N-N-dimethyl-4-hydroxy-3-methoxy-5-fluorobenzylamine. The benzylamine is converted to benzylnitrile and a functional group shuffle is carried out which yields the appropriately substituted benzylcyanide compound. In a composition aspect, the present invention encompasses novel pharmaceutical compositions comprising a compound of the formula I, together with a physiologically acceptable carrier or excipient, in an amount sufficient to increase .beta..sub.2 -adrenergic and antithrombotic activities while simultaneously decreasing the .beta..sub.1 -adrenergic activity in mammals, including humans. The compounds of the invention are useful in the treatment of pulmonary, cardiovascular or thromboembolic disorders.

  本发明涉及一种新型5-氟和8-氟三甲氧喹啉化合物，其通式为I，其中X.sub.1 = F，X.sub.2 = H或X.sub.1 = H，X.sub.2 = F ##STR1## 本发明还涉及一种制备5-氟和8-氟三甲氧喹啉化合物的方法，通过适当取代的苯乙胺缩合以得到适当取代的苯乙基乙酰胺化合物。酰胺环化形成适当取代的中间二氢异喹啉。在不分离的情况下，将二氢异喹啉还原为适当取代的四氢异喹啉。四氢异喹啉的盐酸盐制备并经过氢解作用，得到本发明的氟取代三甲氧喹啉化合物。本发明还包括通过还原适当取代的苄基氰化物制备苯乙胺以及通过将氟取代的甲氧基酚化合物在氨甲基化条件下转化为N- N-二甲基-4-羟基-3-甲氧基-5-氟苄胺来制备中间苄基氰化合物。苄胺转化为苄腈并进行功能基洗牌，得到适当取代的苄基氰化合物。在组成方面，本发明涵盖了包含式I化合物的新型制药组合物，以及与生理学上可接受的载体或赋形剂一起使用，其量足以在哺乳动物中，包括人类中提高β2-肾上腺素能和抗血栓活性，同时降低β1-肾上腺素能活性。本发明的化合物在治疗肺部、心血管或血栓栓塞性疾病方面是有用的。