N'-[2-[2-[2-[[(2S)-2-acetamido-6-[[(2S)-2-amino-6-[[2-[4-(2,6-dioxo-1,3-dipropyl-7H-purin-8-yl)phenoxy]acetyl]amino]hexanoyl]amino]hexanoyl]amino]ethoxy]ethoxy]ethyl]-N-[2-[2-[2-[[4-[[(2S)-6-acetamido-1-amino-1-oxohexan-2-yl]amino]-4-oxobutanoyl]amino]ethoxy]ethoxy]ethyl]butanediamide | 1188000-88-5

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: N'-[2-[2-[2-[[(2S)-2-acetamido-6-[[(2S)-2-amino-6-[[2-[4-(2,6-dioxo-1,3-dipropyl-7H-purin-8-yl)phenoxy]acetyl]amino]hexanoyl]amino]hexanoyl]amino]ethoxy]ethoxy]ethyl]-N-[2-[2-[2-[[4-[[(2S)-6-acetamido-1-amino-1-oxohexan-2-yl]amino]-4-oxobutanoyl]amino]ethoxy]ethoxy]ethyl]butanediamide
• CAS: 1188000-88-5
• 化学式: C₆₁H₉₉N₁₅O₁₇
• 分子量: 1314.55
• InChiKey: YWSDKYTZXCWSTN-QQVWZEJNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -2.6
• 重原子数：
  93
• 可旋转键数：
  52
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.66
• 拓扑面积：
  447
• 氢给体数：
  12
• 氢受体数：
  19

反应信息

• 作为产物：
  描述：

  N-alpha-芴甲氧羰基-N-epsilon-叔丁氧羰基-L-赖氨酸 、 N-[(9H-芴-9-甲氧基)羰基]-N'-[(2-丙烯氧基)羰基]-L-赖氨酸 、 8-(4-羧甲基氧基)苯基-1,3-二丙基黄嘌呤 、 Fmoc-N'-乙酰基-L-赖氨酸 、 12-氧代-5,8-二氧杂-2,11-二氮杂十五烷二酸 1-(9H-芴-9-基甲基)酯 在 1-羟基苯并三唑 、 N,N'-二异丙基碳二亚胺 、 哌啶 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 以3 mg的产率得到N'-[2-[2-[2-[[(2S)-2-acetamido-6-[[(2S)-2-amino-6-[[2-[4-(2,6-dioxo-1,3-dipropyl-7H-purin-8-yl)phenoxy]acetyl]amino]hexanoyl]amino]hexanoyl]amino]ethoxy]ethoxy]ethyl]-N-[2-[2-[2-[[4-[[(2S)-6-acetamido-1-amino-1-oxohexan-2-yl]amino]-4-oxobutanoyl]amino]ethoxy]ethoxy]ethyl]butanediamide
  参考文献：
  名称：

  Adenosine A_2A Receptor-Antagonist/Dopamine D₂ Receptor-Agonist Bivalent Ligands as Pharmacological Tools to Detect A_2A-D₂ Receptor Heteromers

  摘要：

  Adenosine A(2A) (A(2A)R) and dopamine D-2 (D2R) receptors mediate the antagonism between adenosinergic and dopaminergic transmission in striatopallidal GABAergic neurons and are pharmacological targets for the treatment of Parkinson's disease. Here, a family of heterobivalent ligands containing a D,R agonist and an A2AR antagonist linked through a spacer of variable size was designed and synthesized to study A(2A)R-D2R heteromers. Bivalent ligands with shorter linkers bound to D2R or A(2A)R with higher affinity than the corresponding monovalent controls in membranes from brain striatum and from cells coexpressing both receptors. In contrast, no differences in affinity of bivalent versus monovalent ligands were detected in experiments using membranes from cells expressing only one receptor. These findings indicate the existence of A(2A)R-D2R heteromers and of a simultaneous interaction of heterobivalent ligands with both receptors. The cooperative effect derived from the simultaneous interaction suggests the occurrence of A(2A)R-D2R heteromers in cotransfected cells and in brain striatum. The dopamine/adenosine bivalent action could constitute a novel concept in Parkinson's disease pharmacotherapy.

  DOI：

  10.1021/jm900298c

文献信息

• Adenosine A_2A Receptor-Antagonist/Dopamine D₂ Receptor-Agonist Bivalent Ligands as Pharmacological Tools to Detect A_2A-D₂ Receptor Heteromers
  作者：Aroa Soriano、Ruben Ventura、Anabel Molero、Rob Hoen、Vicent Casadó、Antoni Cortés、Francesca Fanelli、Fernando Albericio、Carmen Lluís、Rafael Franco、Miriam Royo

  DOI：10.1021/jm900298c

  日期：2009.9.24

  Adenosine A(2A) (A(2A)R) and dopamine D-2 (D2R) receptors mediate the antagonism between adenosinergic and dopaminergic transmission in striatopallidal GABAergic neurons and are pharmacological targets for the treatment of Parkinson's disease. Here, a family of heterobivalent ligands containing a D,R agonist and an A2AR antagonist linked through a spacer of variable size was designed and synthesized to study A(2A)R-D2R heteromers. Bivalent ligands with shorter linkers bound to D2R or A(2A)R with higher affinity than the corresponding monovalent controls in membranes from brain striatum and from cells coexpressing both receptors. In contrast, no differences in affinity of bivalent versus monovalent ligands were detected in experiments using membranes from cells expressing only one receptor. These findings indicate the existence of A(2A)R-D2R heteromers and of a simultaneous interaction of heterobivalent ligands with both receptors. The cooperative effect derived from the simultaneous interaction suggests the occurrence of A(2A)R-D2R heteromers in cotransfected cells and in brain striatum. The dopamine/adenosine bivalent action could constitute a novel concept in Parkinson's disease pharmacotherapy.