(1R,2R,3S,4R,5S)-4-(2-chloro-6-(isopropylamino)-9H-purin-9-yl)-2',3'-O-(isopropylidene)-bicyclo[3.1.0]hexane | 1312015-40-9

• 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: (1R,2R,3S,4R,5S)-4-(2-chloro-6-(isopropylamino)-9H-purin-9-yl)-2',3'-O-(isopropylidene)-bicyclo[3.1.0]hexane
• CAS: 1312015-40-9
• 化学式: C₁₇H₂₂ClN₅O₂
• 分子量: 363.847
• InChiKey: YWSGPJRFJORQIS-AMGFRPDHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.01
• 重原子数：
  25.0
• 可旋转键数：
  3.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.71
• 拓扑面积：
  74.09
• 氢给体数：
  1.0
• 氢受体数：
  7.0

反应信息

• 作为反应物：
  描述：

  (1R,2R,3S,4R,5S)-4-(2-chloro-6-(isopropylamino)-9H-purin-9-yl)-2',3'-O-(isopropylidene)-bicyclo[3.1.0]hexane 在 三氟乙酸 作用下， 以 甲醇 为溶剂， 反应 6.0h， 以75%的产率得到MRS 5464
  参考文献：
  名称：

  Truncated (N)-Methanocarba Nucleosides as A₁ Adenosine Receptor Agonists and Partial Agonists: Overcoming Lack of a Recognition Element

  摘要：

  A(1) adenosine receptor (AR) agonists are neuroprotective, cardioprotective, and anxiolytic. (N)-Methanocarba adenine nucleosides designed to bind to human A(1)AR were truncated to eliminate 5'-CH2OH. This modification previously converted A(3)AR agonists into antagonists, but the comparable effect at A(1)AR is unknown. In comparison to ribosides, affinity at the A(1)AR was less well preserved than that at the A(3)AR, although a few derivatives were moderately A(1)AR selective, notably full agonist 21 (N-6-dicyclopropyl-methyl, K-i 47.9 nM). Thus, at the A(1)AR, recognition elements for nucleoside binding depend more on 5' region interactions, and in their absence, A(3)AR selectivity predominates. Based on the recently reported agonist-bound AR structure, this difference between subtypes likely correlates with an essential His residue in transmembrane domain 6 of A(1) but not A(3)AR The derivatives ranged from partial to full agonists in A(1)AR-mediated adenylate cyclase inhibition. Truncated derivatives have more druglike physical properties than other A(1)AR agonists; this approach is appealing for preclinical development.

  DOI：

  10.1021/ml200114q
• 作为产物：
  描述：

  2,6-dichloro-9-((3aR,3bR,4aS,5R,5aS)-2,2-dimethylhexahydrocyclopropa[3,4]cyclopenta[1,2-d][1,3]dioxol-5-yl)-9H-purine 、 异丙胺 在 三乙胺 作用下， 以 甲醇 为溶剂， 以75%的产率得到(1R,2R,3S,4R,5S)-4-(2-chloro-6-(isopropylamino)-9H-purin-9-yl)-2',3'-O-(isopropylidene)-bicyclo[3.1.0]hexane
  参考文献：
  名称：

  Truncated (N)-Methanocarba Nucleosides as A₁ Adenosine Receptor Agonists and Partial Agonists: Overcoming Lack of a Recognition Element

  摘要：

  A(1) adenosine receptor (AR) agonists are neuroprotective, cardioprotective, and anxiolytic. (N)-Methanocarba adenine nucleosides designed to bind to human A(1)AR were truncated to eliminate 5'-CH2OH. This modification previously converted A(3)AR agonists into antagonists, but the comparable effect at A(1)AR is unknown. In comparison to ribosides, affinity at the A(1)AR was less well preserved than that at the A(3)AR, although a few derivatives were moderately A(1)AR selective, notably full agonist 21 (N-6-dicyclopropyl-methyl, K-i 47.9 nM). Thus, at the A(1)AR, recognition elements for nucleoside binding depend more on 5' region interactions, and in their absence, A(3)AR selectivity predominates. Based on the recently reported agonist-bound AR structure, this difference between subtypes likely correlates with an essential His residue in transmembrane domain 6 of A(1) but not A(3)AR The derivatives ranged from partial to full agonists in A(1)AR-mediated adenylate cyclase inhibition. Truncated derivatives have more druglike physical properties than other A(1)AR agonists; this approach is appealing for preclinical development.

  DOI：

  10.1021/ml200114q