8-(4-(2-aminopropanoic acid)phenyl)adenosine-5′-monophosphate | 1514900-95-8

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘌呤核苷酸
• 英文名称: 8-(4-(2-aminopropanoic acid)phenyl)adenosine-5′-monophosphate
• CAS: 1514900-95-8
• 化学式: C₆H₁₅N*C₁₉H₂₃N₆O₉P
• 分子量: 611.592
• InChiKey: ANOIOZUPWONORT-RSZDFXOBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.11
• 重原子数：
  42.0
• 可旋转键数：
  11.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  252.63
• 氢给体数：
  7.0
• 氢受体数：
  13.0

反应信息

• 作为产物：
  描述：

  8-bromoadenosine 5′-diphosphate ribose 、 4-二羟基硼基-DL-苯丙氨酸 、 三乙基碳酸氢铵缓冲液 在 trisodium tris(3-sulfophenyl)phosphine 、 palladium diacetate 、 caesium carbonate 作用下， 以 水 、 乙腈 为溶剂， 反应 0.08h， 以18%的产率得到8-(4-(2-aminopropanoic acid)phenyl)adenosine-5′-monophosphate
  参考文献：
  名称：

  Structure–Activity Relationship of Adenosine 5′-diphosphoribose at the Transient Receptor Potential Melastatin 2 (TRPM2) Channel: Rational Design of Antagonists

  摘要：

  Adenosine S'-diphosphoribose (ADPR) activates TRPM2, a Ca2+, Na+, and K+ permeable cation channel. Activation is induced by ADPR binding to the cytosolic C-terminal NudT9-homology domain. To generate the first structure activity relationship, systematically modified ADPR analogues were designed, synthesized, and evaluated as antagonists using patch-clamp experiments in HEK293 cells overexpressing human TRPM2. Compounds with a purine C8 substituent show antagonist activity, and an 8-phenyl substitution (8-Ph-ADPR, 5) is very effective. Modification of the terminal ribose results in a weak antagonist, whereas its removal abolishes activity. An antagonist based upon a hybrid structure, 8-phenyl-2'-deoxy-ADPR (86, IC50 = 3 mu M), is more potent than 8-Ph-ADPR (5). Initial bioisosteric replacement of the pyrophosphate linkage abolishes activity, but replacement of the pyrophosphate and the terminal ribose by a sulfarnate-based group leads to a weak antagonist, a lead to more drug-like analogues. 8-Ph-ADPR (5) inhibits Ca2+ signalling and chemotaxis in human neutrophils, illustrating the potential for pharmacological intervention at TRPM2.

  DOI：

  10.1021/jm401497a