1-(2′,3′-O-isopropylidene-5′-deoxy-8-phenyladenosine)-4-(2″,3″-O-isopropylidene-5″-O-methylribosyl)-1,2,3-triazole | 1514901-20-2

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘌呤核苷
• 英文名称: 1-(2′,3′-O-isopropylidene-5′-deoxy-8-phenyladenosine)-4-(2″,3″-O-isopropylidene-5″-O-methylribosyl)-1,2,3-triazole
• CAS: 1514901-20-2
• 化学式: C₃₁H₃₈N₈O₈
• 分子量: 650.692
• InChiKey: CMGCYSFSCDRKHH-FIVPDNSCSA-N

物化性质

• 沸点：
  833.7±75.0 °C(predicted)
• 密度：
  1.61±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.19
• 重原子数：
  47.0
• 可旋转键数：
  9.0
• 环数：
  8.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  174.17
• 氢给体数：
  1.0
• 氢受体数：
  16.0

反应信息

• 作为反应物：
  描述：

  1-(2′,3′-O-isopropylidene-5′-deoxy-8-phenyladenosine)-4-(2″,3″-O-isopropylidene-5″-O-methylribosyl)-1,2,3-triazole 在 硫酸 作用下， 反应 16.0h， 以24%的产率得到1-(5′-deoxy-8-phenyladenosine)-4-(2″,3″-O-isopropylidene-5″-O-methylribosyl)-1,2,3-triazole
  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：

  2',3'-异丙叉腺苷 在 copper(ll) sulfate pentahydrate 、 sodium tetrachloropalladate(II) 、 二苯基膦叠氮化物 、 trisodium tris(3-sulfophenyl)phosphine 、 溴 、 sodium carbonate 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 sodium ascorbate 作用下， 以 1,4-二氧六环 、 水 、 乙腈 、 叔丁醇 为溶剂， 反应 48.0h， 生成 1-(2′,3′-O-isopropylidene-5′-deoxy-8-phenyladenosine)-4-(2″,3″-O-isopropylidene-5″-O-methylribosyl)-1,2,3-triazole
  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