8-(succinylamido-3-propylamino)adenine | 918529-72-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 咪唑并嘧啶类
• 英文名称: 8-(succinylamido-3-propylamino)adenine
• 英文别名: 4-[3-[(6-amino-7H-purin-8-yl)amino]propylamino]-4-oxobutanoic acid
• CAS: 918529-72-3
• 化学式: C₁₂H₁₇N₇O₃
• 分子量: 307.312
• InChiKey: CKYJQTQOQSJWCE-UHFFFAOYSA-N

物化性质

• 密度：
  1.514±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.3
• 重原子数：
  22
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  159
• 氢给体数：
  5
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  8-(succinylamido-3-propylamino)adenine 、 alkaline earth salt of/the/ methylsulfuric acid 在 1-羟基苯并三唑 、 O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 、 三异丙基硅烷 、 三氟乙酸 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 3.0h， 生成 N'-[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-amino-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]-N-[3-[(6-amino-7H-purin-8-yl)amino]propyl]butanediamide
  参考文献：
  名称：

  Conjugation of Adenosine and Hexa-(d-arginine) Leads to a Nanomolar Bisubstrate-Analog Inhibitor of Basophilic Protein Kinases

  摘要：

  Conjugates of oligoarginine peptides with adenine, adenosine, adenosine-5'-carboxylic acid, and 5-isoquino-linesulfonic acid were synthesized and characterized as bisubstrate-analog inhibitors of cAMP-dependent protein kinase. Adenosine and adenine derivatives were connected to the N- or C-terminus of peptides containing four to six L- or D-arginine residues via a linker with a length that had been optimized in structure-activity studies. The orientation of the peptide chain strongly affected the activity of compounds incorporating D-arginines. The biligand inhibitor containing Hidaka's H9 isoquinolinesulfonamide connected to the L- peptide had 65 times higher potency than the corresponding adenosine-containing conjugate, while both types of the conjugate comprising D-peptides had similar low nanomolar activity. Two of the most active adenosine-and H9-peptide conjugates were tested in the panel of 52 different kinases. At 1 mu M concentration, both compounds showed strong (more than 95%) inhibition of several basophilic AGC kinases, including pharmaceutically important kinases ROCK II and PKB/Akt.

  DOI：

  10.1021/jm0605942
• 作为产物：
  描述：

  8-溴腺嘌呤 在 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 24.42h， 生成 8-(succinylamido-3-propylamino)adenine
  参考文献：
  名称：

  Conjugation of Adenosine and Hexa-(d-arginine) Leads to a Nanomolar Bisubstrate-Analog Inhibitor of Basophilic Protein Kinases

  摘要：

  Conjugates of oligoarginine peptides with adenine, adenosine, adenosine-5'-carboxylic acid, and 5-isoquino-linesulfonic acid were synthesized and characterized as bisubstrate-analog inhibitors of cAMP-dependent protein kinase. Adenosine and adenine derivatives were connected to the N- or C-terminus of peptides containing four to six L- or D-arginine residues via a linker with a length that had been optimized in structure-activity studies. The orientation of the peptide chain strongly affected the activity of compounds incorporating D-arginines. The biligand inhibitor containing Hidaka's H9 isoquinolinesulfonamide connected to the L- peptide had 65 times higher potency than the corresponding adenosine-containing conjugate, while both types of the conjugate comprising D-peptides had similar low nanomolar activity. Two of the most active adenosine-and H9-peptide conjugates were tested in the panel of 52 different kinases. At 1 mu M concentration, both compounds showed strong (more than 95%) inhibition of several basophilic AGC kinases, including pharmaceutically important kinases ROCK II and PKB/Akt.

  DOI：

  10.1021/jm0605942

文献信息

• BISUBSTRATE FLUORESCENT PROBE BINDING TO PROTEIN KINASES
  申请人：Uri Asko

  公开号：US20100233743A1

  公开（公告）日：2010-09-16

  This invention relates to fluorescent probes for identification of compounds binding to protein kinases, for measurement of the affinity of inhibitors of protein kinases, and determination of the active concentration of protein kinases binding to the probe. Bisubstrate-analog character of the probe enables the simultaneous evaluation of inhibitors targeted to both ATP binding site and/or substrate protein/peptide binding domain of the kinase. High affinity of the probe (K d =1.0 nM towards cAMP-dependent protein kinase) affords the application of the enzymes at low concentration which leads to the substantial decrease of the consumption of the kinase. Due to the ability of the conjugates of oligo(D-arginine) with a ATP binding site targeted inhibitors of this invention to bind with high affinity to a wide spectrum of (basophilic) kinases, a single Fluorescent probe is applicable for assessment of inhibitory potency of compounds towards a great number of protein kinases.
• US8158376B2
  申请人：——

  公开号：US8158376B2

  公开（公告）日：2012-04-17
• Conjugation of Adenosine and Hexa-(<scp>d</scp>-arginine) Leads to a Nanomolar Bisubstrate-Analog Inhibitor of Basophilic Protein Kinases
  作者：Erki Enkvist、Darja Lavogina、Gerda Raidaru、Angela Vaasa、Indrek Viil、Marje Lust、Kaido Viht、Asko Uri

  DOI：10.1021/jm0605942

  日期：2006.11.30

  Conjugates of oligoarginine peptides with adenine, adenosine, adenosine-5'-carboxylic acid, and 5-isoquino-linesulfonic acid were synthesized and characterized as bisubstrate-analog inhibitors of cAMP-dependent protein kinase. Adenosine and adenine derivatives were connected to the N- or C-terminus of peptides containing four to six L- or D-arginine residues via a linker with a length that had been optimized in structure-activity studies. The orientation of the peptide chain strongly affected the activity of compounds incorporating D-arginines. The biligand inhibitor containing Hidaka's H9 isoquinolinesulfonamide connected to the L- peptide had 65 times higher potency than the corresponding adenosine-containing conjugate, while both types of the conjugate comprising D-peptides had similar low nanomolar activity. Two of the most active adenosine-and H9-peptide conjugates were tested in the panel of 52 different kinases. At 1 mu M concentration, both compounds showed strong (more than 95%) inhibition of several basophilic AGC kinases, including pharmaceutically important kinases ROCK II and PKB/Akt.