4-(9-diethylamino-5-oxo-5H-benzo[a]phenoxazin-2-yloxy)-butyric acid allyl ester | 1018900-38-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并恶嗪类
• 英文名称: 4-(9-diethylamino-5-oxo-5H-benzo[a]phenoxazin-2-yloxy)-butyric acid allyl ester
• 英文别名: prop-2-enyl 4-[9-(diethylamino)-5-oxobenzo[a]phenoxazin-2-yl]oxybutanoate
• CAS: 1018900-38-3
• 化学式: C₂₇H₂₈N₂O₅
• 分子量: 460.53
• InChiKey: YCECMOLUDOERHQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  34
• 可旋转键数：
  11
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  77.4
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  4-(9-diethylamino-5-oxo-5H-benzo[a]phenoxazin-2-yloxy)-butyric acid allyl ester 在 N,N-二异丙基乙胺 作用下， 以 二甲基亚砜 为溶剂， 反应 1.5h， 以78%的产率得到4-(6-bromo-9-diethylamino-5-oxo-5H-benzo[a]phenoxazin-2-yloxy)-butyric acid allyl ester
  参考文献：
  名称：

  Probing lipid- and drug-binding domains with fluorescent dyes

  摘要：

  A series of 2- and 3-OH Nile red dyes was prepared in order to generate water-soluble probes that could be used to probe lipid binding to proteins. Various substitutions in positions 243-, 6-, and 7-shifted wavelengths while maintaining the environmental sensitivity of Nile red. In order to increase the solubility of the dyes in aqueous solutions, we attached butyric acid groups to the 2- or 3-OH position. In addition., phenothiazine dyes, which exhibited particularly long excitation properties, were synthesized and tested for the first time. All dyes showed Stoke's shifts of 70-100 nm and changes in excitation and emission of over 100 nm, depending on the hydrophobicity of the environment. Binding studies with bovine serum albumin and the non-specific lipid transfer protein SCP2 revealed emission changes of more than 30 nm upon binding to the protein and a five-fold increase in emission intensity. Titration of the dye-loaded proteins with various lipids or drugs replaced the dye and thereby reversed the shift in wavelength intensity. This allowed us to estimate the lipid binding affinity of the investigated proteins. For SCP2, isothermal calorimetry (ITC) data verified the titration experiments. NMR titration experiments of SCP2 with Nile red 2-O-butyric acid (1a) revealed that the dye is bound within the lipid binding pocket and competes with lipid ligands for this binding site. These results give valuable insight into lipid and drug transport by proteins outside and inside cells. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2007.10.080
• 作为产物：
  描述：

  4-溴丁酸烯丙基酯 、 9-(diethylamino)-5-hydroxybenzo[a]phenoxazin-2-one 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 8.0h， 以43%的产率得到4-(9-diethylamino-5-oxo-5H-benzo[a]phenoxazin-2-yloxy)-butyric acid allyl ester
  参考文献：
  名称：

  Probing lipid- and drug-binding domains with fluorescent dyes

  摘要：

  A series of 2- and 3-OH Nile red dyes was prepared in order to generate water-soluble probes that could be used to probe lipid binding to proteins. Various substitutions in positions 243-, 6-, and 7-shifted wavelengths while maintaining the environmental sensitivity of Nile red. In order to increase the solubility of the dyes in aqueous solutions, we attached butyric acid groups to the 2- or 3-OH position. In addition., phenothiazine dyes, which exhibited particularly long excitation properties, were synthesized and tested for the first time. All dyes showed Stoke's shifts of 70-100 nm and changes in excitation and emission of over 100 nm, depending on the hydrophobicity of the environment. Binding studies with bovine serum albumin and the non-specific lipid transfer protein SCP2 revealed emission changes of more than 30 nm upon binding to the protein and a five-fold increase in emission intensity. Titration of the dye-loaded proteins with various lipids or drugs replaced the dye and thereby reversed the shift in wavelength intensity. This allowed us to estimate the lipid binding affinity of the investigated proteins. For SCP2, isothermal calorimetry (ITC) data verified the titration experiments. NMR titration experiments of SCP2 with Nile red 2-O-butyric acid (1a) revealed that the dye is bound within the lipid binding pocket and competes with lipid ligands for this binding site. These results give valuable insight into lipid and drug transport by proteins outside and inside cells. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2007.10.080

文献信息

• Fluorescent Method And Compounds To Monitor Protein-Lipid Binding
  申请人：Schultz Carsten

  公开号：US20080038840A1

  公开（公告）日：2008-02-14

  The invention refers to compounds according to formula (I), wherein R 1 is independently in position 2′, 3′, or in both positions of the A ring and is hydroxyl, linear or branched -0-alkyl, wherein the alkyl group has 1-12 carbon atoms, preferably 3-8, more preferably 4 carbon —O-(alkyl)COOH wherein the alkyl group has 1-12 carbon atoms, preferably 3-8, more preferably 4 carbon atoms, —O-(aryl)COOH, -0-aryl, linear or branched —O—(CH 2 ) m —CH(NH 2 )—COOH with m=1-6, preferably m=2-4, or any combination thereof; R 4 is in position 8′, 10′, or 11′ of the D ring of the compound and is H or (CH 2 ) n —CH 3 with n=0-6, COOH, CN, or halogen, R 5 and R 6 independently are ethyl-, methyl-, H, or —(CH 2 ) 3 connected to position 8 or 10 of the D ring, and wherein provided that X is O, R 2 is F, Cl, Br, I, H, CN, —CH═CH-alkyl, —C═—C-alkyl, aryl and R 3 is F, Cl, Br, I, CN, —CH═CH-alkyl, —C═C-alkyl, aryl an provided that X is S, R 2 and R 3 independently are F, Cl, Br, I, H, CN, —CH═CH-alkyl, —C═C-alkyl, aryl. The invention further refers to the use of the compounds according to formula (I), wherein R 1 , R 4 , R 5 and R 6 are defined as aforementioned and wherein R 2 and R 3 independently are F, Cl, Br, I, H, CN, —CH═CH-alkyl, —C═—C-alkyl, or aryl, and wherein X is O or S, as environmentally sensitive fluorescent dyes, particularly in an assay for identifying proteinlipid interactions.

  该发明涉及公式（I）的化合物，其中R1独立于A环的2'、3'位置或两个位置，并且为羟基，线性或支链状-0-烷基，其中烷基具有1-12个碳原子，优选3-8个，更优选4个碳-O-（烷基）COOH，其中烷基具有1-12个碳原子，优选3-8个，更优选4个碳原子，-O-（芳基）COOH，-0-芳基，线性或支链状-O-（CH2）m-CH（NH2）-COOH，其中m = 1-6，优选m = 2-4或任何组合；R4在化合物的D环的8'、10'或11'位置，并且为H或（CH2）n-CH3，其中n = 0-6，COOH，CN或卤素，R5和R6独立地为乙基，甲基，H或-（CH2）3连接到D环的8或10位置，其中如果X为O，则R2为F，Cl，Br，I，H，CN，-CH═CH-烷基，-C═-C-烷基，芳基，而R3为F，Cl，Br，I，CN，-CH═CH-烷基，-C═C-烷基，芳基，如果X为S，则R2和R3独立地为F，Cl，Br，I，H，CN，-CH═CH-烷基，-C═C-烷基，芳基。该发明还涉及公式（I）的化合物的用途，其中R1、R4、R5和R6如上所述，并且R2和R3独立地为F，Cl，Br，I，H，CN，-CH═CH-烷基，-C═-C-烷基或芳基，而X为O或S，作为环境敏感荧光染料，特别是在识别蛋白质脂质相互作用的分析中。
• FLUORESCENT METHOD AND COMPOUNDS TO MONITOR PROTEIN-LIPID BINDING
  申请人：EUROPÄISCHES LABORATORIUM FÜR MOLEKULARBIOLOGIE (EMBL)

  公开号：EP1747207A1

  公开（公告）日：2007-01-31
• [EN] FLUORESCENT METHOD AND COMPOUNDS TO MONITOR PROTEIN-LIPID BINDING<br/>[FR] PROCEDE PAR FLUORESCENCE ET COMPOSES POUR LA SURVEILLANCE DE LA LIAISON PROTEINES-LIPIDES
  申请人：EUROP LAB MOLEKULARBIOLOG

  公开号：WO2005113524A1

  公开（公告）日：2005-12-01

  The invention refers to compounds according to formula (I), wherein Rl is independently in position 2', 3', or in both positions of the A ring and is hydroxyl, linear or branched -0-alkyl, wherein the alkyl group has 1-12 carbon atoms, preferably 3-8, more preferably 4 carbon atoms, -O-(alkyl)COOH wherein the alkyl group has 1-12 carbon atoms, preferably 3-8, more preferably 4 carbon atoms, -O-(aryl)COOH, -0-aryl, linear or branched -O-(CH2)m-CH(NH2)-COOH with m = 1-6, preferably m= 2-4, or any combination thereof; R4 is in position 8', 10', or 1 l' of the D ring of the compound and is H or (CH2)n -CH3 with n = 0-6, COOH, CN, or halogen, R5 and R6 independently are ethyl-, methyl-, H, or -(CH2)3 connected to position 8 or 10 of the D ring, and wherein provided that X is O, R2 is F, Cl, Br, I, H, CN, -CH=CH-alkyl, -C =- C-alkyl, aryl and R3 is F, Cl, Br, I, CN, -CH=CH-alkyl, -C = C-alkyl, aryl and provided that X is S, R2 and R3 independently are F, Cl, Br, I, H, CN, -CH=CH-alkyl, - C=C-alkyl, aryl. The invention further refers to the use of the compounds according to formula (I), wherein R1, R4, R5 and R6 are defined as aforementioned and wherein R2 and R3 independently are F, Cl, Br, I, H, CN, -CH=CH-alkyl, -C=-C-alkyl, or aryl, and wherein X is O or S, as environmentally sensitive fluorescent dyes, particularly in an assay for identifying proteinlipid interactions.
• Probing lipid- and drug-binding domains with fluorescent dyes
  作者：Shannon L. Black、Will A. Stanley、Fabian V. Filipp、Michelle Bhairo、Ashwani Verma、Oliver Wichmann、Michael Sattler、Matthias Wilmanns、Carsten Schultz

  DOI：10.1016/j.bmc.2007.10.080

  日期：2008.2.1

  A series of 2- and 3-OH Nile red dyes was prepared in order to generate water-soluble probes that could be used to probe lipid binding to proteins. Various substitutions in positions 243-, 6-, and 7-shifted wavelengths while maintaining the environmental sensitivity of Nile red. In order to increase the solubility of the dyes in aqueous solutions, we attached butyric acid groups to the 2- or 3-OH position. In addition., phenothiazine dyes, which exhibited particularly long excitation properties, were synthesized and tested for the first time. All dyes showed Stoke's shifts of 70-100 nm and changes in excitation and emission of over 100 nm, depending on the hydrophobicity of the environment. Binding studies with bovine serum albumin and the non-specific lipid transfer protein SCP2 revealed emission changes of more than 30 nm upon binding to the protein and a five-fold increase in emission intensity. Titration of the dye-loaded proteins with various lipids or drugs replaced the dye and thereby reversed the shift in wavelength intensity. This allowed us to estimate the lipid binding affinity of the investigated proteins. For SCP2, isothermal calorimetry (ITC) data verified the titration experiments. NMR titration experiments of SCP2 with Nile red 2-O-butyric acid (1a) revealed that the dye is bound within the lipid binding pocket and competes with lipid ligands for this binding site. These results give valuable insight into lipid and drug transport by proteins outside and inside cells. (c) 2007 Elsevier Ltd. All rights reserved.