4-chloromethyl-6,8-difluoro-7-hydroxy-coumarin

• 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: 4-chloromethyl-6,8-difluoro-7-hydroxy-coumarin
• 英文别名: CellTracker Blue CMF2HC Dye；4-(chloromethyl)-6,8-difluoro-7-hydroxychromen-2-one
• 化学式: C₁₀H₅ClF₂O₃
• 分子量: 246.598
• InChiKey: QDLNIWVLVXWCPH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  16
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  46.5
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  4-chloromethyl-6,8-difluoro-7-hydroxy-coumarin 在 甲醇 、 sodium methylate 、 silver carbonate 、 sodium sulfite 作用下， 以 乙醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 生成 sodium β-D-glucoside 6,8-difluoro-7-hydroxycoumarin-4-methanesulfonate
  参考文献：
  名称：

  SULFONATED COUMARINS, SYNTHESIS THEREOF, FLUOROGENIC SUBSTRATES RESULTING FROM GRAFTING SAID COUMARINS ONTO SUGARS, METHOD FOR PREPARING SAID SUBSTRATES, AND USES THEREOF

  摘要：

  取代的磺化香豆素在一般公式（I）中表示，其中：R1是H、OH，或者是取代的或未取代的直链或支链C1-C6烷基自由基，或者—COR4，或者—COOR4，或者—CONHR4，R2是H或卤素，特别是氟，或者是取代的或未取代的直链或支链C1-C6烷基自由基，或者—COR4，或者—COOR4，或者—CONHR4，R1和R2能够共同形成一个环，如取代的或未取代的芳基或呋喃，R3是H或卤素，特别是氟，或者是取代的或未取代的直链或支链C1-C6烷基自由基，或者—COR4，或者—COOR4，或者—CONHR4，其中R4是H，或者是取代的或未取代的直链或支链C1-C6烷基自由基，或者取代的或未取代的芳基，M是Na或K。

  公开号：

  US20130183700A1
• 作为产物：
  描述：

  4-氯乙酰乙酸乙酯 、 2,4-二氟邻苯二酚 在 水 作用下， 以 甲烷磺酸 为溶剂， 反应 2.5h， 以to give the title compound as a colourless powder (2.25 g, 67%)的产率得到4-chloromethyl-6,8-difluoro-7-hydroxy-coumarin
  参考文献：
  名称：

  PROCESS FOR PRODUCING RADIOHALOGENATED BIOCONJUGATES AND PRODUCTS THEREOF

  摘要：

  本发明涉及一种新的合成过程，其中炔烃和叠氮化物反应形成放射性同位素生物共轭构建物。该反应特别适用于生产用于成像和放射治疗应用的化合物。本发明还提供了生物共轭标签，并涉及使用这些化合物进行诊断和治疗方法。此外，本发明还提供了一种相关的过程，用于将放射性卤素原子引入末端炔烃中。

  公开号：

  US20130209361A1

文献信息

• [EN] THIOARYL DERIVATIVES AS GPR120 AGONISTS<br/>[FR] DÉRIVÉS DE THIOARYLE À TITRE D'AGONISTES DE GPR120
  申请人：LG LIFE SCIENCES LTD

  公开号：WO2014069963A1

  公开（公告）日：2014-05-08

  The present invention relates to thioaryl derivatives of Formula 1 as defined in the specification, a method for preparing the same, a pharmaceutical composition comprising the same and use thereof. The thioaryl derivatives of Formula 1 according to the present invention promote GLP-1 formation in the gastrointestinal tract and improve insulin resistance in macrophages, pancreas cells, etc. due to anti-inflammatory action, and can accordingly be effectively used for preventing or treating diabetes, complications of diabetes, inflammation, obesity, non-alcoholic fatty liver, steatohepatitis or osteoporosis.

  本发明涉及规范中定义的Formula 1的硫代芳基衍生物，一种制备该衍生物的方法，包含该衍生物的药物组合物以及其用途。根据本发明，Formula 1的硫代芳基衍生物促进胃肠道中GLP-1的形成，并通过抗炎作用改善巨噬细胞、胰腺细胞等的胰岛素抵抗，因此可以有效用于预防或治疗糖尿病、糖尿病并发症、炎症、肥胖、非酒精性脂肪肝、脂肪性肝炎或骨质疏松症。
• Derivatives of 6,8-difluoro-7-hydroxycoumarin
  申请人：Molecular Probes, Inc.

  公开号：US05830912A1

  公开（公告）日：1998-11-03

  The present invention comprises 6,8-difluoro-7-hydroxycoumarins and derivatives of 6,8-difluoro-7-hydroxycoumarins, including reactive dyes, dye-conjugates and enzyme substrates. These fluorine-substituted fluorescent dyes typically possess greater photostability and lower pH sensitivity in the physiological pH range than their nonfluorinated analogs, exhibit less fluorescence quenching when conjugated to a substance, possess absorption and emission spectra that closely match those of their nonfluorinated analogs, and also exhibit higher quantum yields than their nonfluorinated analogs.

  本发明包括6,8-二氟-7-羟基香豆素及其衍生物，包括反应染料、染料共轭物和酶底物。这些氟取代的荧光染料通常具有比其非氟取代的类似物在生理pH范围内更高的光稳定性和较低的pH敏感性，当与物质结合时，表现出较少的荧光猝灭，具有吸收和发射光谱与其非氟取代的类似物非常接近，并且比其非氟取代的类似物具有更高的量子产率。
• Sulfonated coumarins, their synthesis, fluorogenic substrates resulting from grafting of these coumarins on sugars, method for obtaining these substrates, and their applications
  申请人：Drevelle Antoine

  公开号：US08716496B2

  公开（公告）日：2014-05-06

  Substituted sulfonated coumarins are expressed in the general formula (I), where: R1 is H, OH, or a substituted or unsubstituted, straight or branched C1-C6 alkyl radical, or —COR4, or —COOR4, or —CONHR4, R2 is H or a halogen, in particular fluorine, or a substituted or unsubstituted, straight or branched C1-C6 alkyl radical, or —COR4, or —COOR4, or —CONHR4, R1 and R2 being capable of together forming a ring, such as a substituted or unsubstituted aryl or furane, R3 is H or a halogen, in particular fluorine, or a substituted or unsubstituted, straight or branched C1-C6 alkyl radical, or —COR4, or —COOR4, or —CONHR4, where R4 is H, or a substituted or unsubstituted, straight or branched C1-C6 alkyl radical, or a substituted or unsubstituted aryl, and M is Na or K.

  取代磺化香豆素的一般式为（I），其中：R1为H，OH或取代或未取代的直链或支链C1-C6烷基基团，或-COR4，或-COOR4，或-CONHR4，R2为H或卤素，特别是氟，或取代或未取代的直链或支链C1-C6烷基基团，或-COR4，或-COOR4，或-CONHR4，R1和R2能够共同形成环，例如取代或未取代的芳基或呋喃基，R3为H或卤素，特别是氟，或取代或未取代的直链或支链C1-C6烷基基团，或-COR4，或-COOR4，或-CONHR4，其中R4为H，或取代或未取代的直链或支链C1-C6烷基基团，或取代或未取代的芳基，M为Na或K。
• FLUOROGENIC SUBSTRATES, METHODS OF MAKING THE SUBSTRATES, AND METHODS OF DETECTING GLYCOSIDASE ACTIVITIES
  申请人：UNIVERSITE DE STRASBOURG

  公开号：US20140234884A1

  公开（公告）日：2014-08-21

  Fluorogenic substrates, methods of making the fluorogenic substrates, and methods of detecting glycosidase activities (EC3.2.1) are provided. The fluorogenic substrates are composed of a sugar covalently bonded to the 7-hydroxy position of a substituted coumarin sulfonated fluorophore is provided. The fluorogenic substrates include sodium β-D-cellobioside 6,8-difluoro-7-hydroxycoumarin-4-methanesulfonate; sodium β-D-glucoside 6,8-difluoro-7-hydroxycoumarin-4-methanesulfonate; sodium β-D-xyloside 6,8-difluoro-7-hydroxycoumarin-4-methanesulfonate; sodium β-D-xylobioside 6,8-difluoro-7-hydroxycoumarin-4-methanesulfonate; and sodium β-D-xylopolyoside 6,8-difluoro-7-hydroxycoumarin-4-methanesulfonate. The fluorogenic substrates may be made by covalently bonding the sugar moiety to the 7-hydroxy position of the substituted coumarin sulfonated fluorophore by reaction in DMF. Glycosidase activities can be detected in enzymatic extracts, microorganisms, and cells by contacting the extracts, microorganisms, or cells with one of the fluorogenic substrates.

  本发明提供了荧光底物、制备荧光底物的方法以及检测糖苷酶(EC3.2.1)活性的方法。荧光底物由一种糖与取代香豆素磺化荧光物的7-羟基位置共价结合而成。荧光底物包括：β-D-纤维二糖钠盐6,8-二氟-7-羟基香豆素-4-甲烷磺酸酯；β-D-葡萄糖苷钠盐6,8-二氟-7-羟基香豆素-4-甲烷磺酸酯；β-D-木糖苷钠盐6,8-二氟-7-羟基香豆素-4-甲烷磺酸酯；β-D-木二糖钠盐6,8-二氟-7-羟基香豆素-4-甲烷磺酸酯；β-D-木多糖钠盐6,8-二氟-7-羟基香豆素-4-甲烷磺酸酯。荧光底物可通过在DMF中反应，将糖基与取代香豆素磺化荧光物的7-羟基位置共价结合制备而成。可通过将提取物、微生物或细胞与荧光底物之一接触来检测糖苷酶活性。
• THIOARYL DERIVATIVES AS GPR120 AGONISTS
  申请人：LG LIFE SCIENCES LTD.

  公开号：US20150291527A1

  公开（公告）日：2015-10-15

  The present invention relates to thioaryl derivatives of Formula 1 as defined in the specification, a method for preparing the same, a pharmaceutical composition comprising the same and use thereof. The thioaryl derivatives of Formula 1 according to the present invention promote GLP-1 formation in the gastrointestinal tract and improve insulin resistance in macrophages, pancreas cells, etc. due to anti-inflammatory action, and can accordingly be effectively used for preventing or treating diabetes, complications of diabetes, inflammation, obesity, non-alcoholic fatty liver, steatohepatitis or osteoporosis.

  本发明涉及公式1中定义的硫代芳基衍生物，其制备方法，包含其的药物组合物以及使用方法。本发明中的公式1中的硫代芳基衍生物能够促进胃肠道中的GLP-1形成，并通过抗炎作用改善巨噬细胞、胰腺细胞等的胰岛素抵抗力，因此可以有效用于预防或治疗糖尿病、糖尿病并发症、炎症、肥胖症、非酒精性脂肪肝、脂肪性肝炎或骨质疏松症。