3-(2′,3′-O-isopropylidene-5′-amino-5′-deoxyadenosine)-4-(cyclopentylamino)-cyclobut-3-ene-1,2-dione | 1514901-11-1

• 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: 3-(2′,3′-O-isopropylidene-5′-amino-5′-deoxyadenosine)-4-(cyclopentylamino)-cyclobut-3-ene-1,2-dione
• CAS: 1514901-11-1
• 化学式: C₂₂H₂₇N₇O₅
• 分子量: 469.5
• InChiKey: BRYYLDUKBPMYRA-PTCKGGSZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.89
• 重原子数：
  34.0
• 可旋转键数：
  6.0
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.59
• 拓扑面积：
  155.51
• 氢给体数：
  3.0
• 氢受体数：
  12.0

反应信息

• 作为反应物：
  描述：

  3-(2′,3′-O-isopropylidene-5′-amino-5′-deoxyadenosine)-4-(cyclopentylamino)-cyclobut-3-ene-1,2-dione 在 三氟乙酸 作用下， 以 水 为溶剂， 反应 1.0h， 以85%的产率得到3-(5′-amino-5′-deoxyadenosine)-4-(cyclopentylamino)-cyclobut-3-ene-1,2-dione
  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
• 作为产物：
  描述：

  5'-azido-5'-deoxy-2',3'-O-isopropylidene adenosine 在 palladium 10% on activated carbon 、 氢气 、 N,N-二异丙基乙胺 作用下， 以 乙醇 为溶剂， 反应 17.0h， 生成 3-(2′,3′-O-isopropylidene-5′-amino-5′-deoxyadenosine)-4-(cyclopentylamino)-cyclobut-3-ene-1,2-dione
  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