(1R,2R,3S,4R,5S)-4-(6-(3-chlorobenzylamino)-2-(phenylethynyl)-9H-purin-9-yl)bicyclo[3.1.0]hexane-2,3-diol | 1383554-38-8

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 核苷和核苷酸类似物
• 英文名称: (1R,2R,3S,4R,5S)-4-(6-(3-chlorobenzylamino)-2-(phenylethynyl)-9H-purin-9-yl)bicyclo[3.1.0]hexane-2,3-diol
• 英文别名: (1R,2R,3S,4R,5S)-4-[6-[(3-chlorophenyl)methylamino]-2-(2-phenylethynyl)purin-9-yl]bicyclo[3.1.0]hexane-2,3-diol
• CAS: 1383554-38-8
• 化学式: C₂₆H₂₂ClN₅O₂
• 分子量: 471.946
• InChiKey: VWOHRLFZGZDIDJ-CQRLQNNPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  34
• 可旋转键数：
  6
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  96.1
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  2-碘-6-氯嘌呤 在 bis-triphenylphosphine-palladium(II) chloride 、 copper(l) iodide 、 三氟甲磺酸 、 偶氮二甲酸二异丙酯 、 三乙胺 、 三苯基膦 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 生成 (1R,2R,3S,4R,5S)-4-(6-(3-chlorobenzylamino)-2-(phenylethynyl)-9H-purin-9-yl)bicyclo[3.1.0]hexane-2,3-diol
  参考文献：
  名称：

  Truncated Nucleosides as A₃ Adenosine Receptor Ligands: Combined 2-Arylethynyl and Bicyclohexane Substitutions

  摘要：

  C2-Arylethynyladenosine-5'-N-methyluronamides containing a bicyclo[3.1.0]hexane [(N)-methanocarba] ring are selective A(3) adenosine receptor (AR) agonists. Similar 4'-truncated C2-arylethynyl-(N)-methanocarba nucleosides containing alkyl or alkylaryl groups at the N-6 position were low-efficacy agonists or antagonists of the human A(3)AR with high selectivity. Higher hA(3)AR affinity was associated with N-6-methyl and ethyl (K-i = 3-6 nM) than with N-6-arylallcyl groups. However, combined C2-phenylethynyl and N-6-2-phenylethyl substitutions in selective antagonist 15 provided a K-i of 20 nM. Differences between 4'-truncated and nontruncated analogues of extended C2-p-biphenylethynyl substitution suggested a ligand reorientation in AR binding, dominated by bulky N-6 groups in analogues lacking a stabilizing S'-uronamide moiety. Thus, 4'-truncation of C2-arylethynyl-(N)-methanocarba adenosine derivatives is compatible with general preservation of A(3)AR selectivity, especially with small N-6 groups, but reduced efficacy in A(3)AR-induced inhibition of adenylate cyclase.

  DOI：

  10.1021/ml300107e

文献信息

• Truncated Nucleosides as A₃ Adenosine Receptor Ligands: Combined 2-Arylethynyl and Bicyclohexane Substitutions
  作者：Dilip K. Tosh、Silvia Paoletta、Khai Phan、Zhan-Guo Gao、Kenneth A. Jacobson

  DOI：10.1021/ml300107e

  日期：2012.7.12

  C2-Arylethynyladenosine-5'-N-methyluronamides containing a bicyclo[3.1.0]hexane [(N)-methanocarba] ring are selective A(3) adenosine receptor (AR) agonists. Similar 4'-truncated C2-arylethynyl-(N)-methanocarba nucleosides containing alkyl or alkylaryl groups at the N-6 position were low-efficacy agonists or antagonists of the human A(3)AR with high selectivity. Higher hA(3)AR affinity was associated with N-6-methyl and ethyl (K-i = 3-6 nM) than with N-6-arylallcyl groups. However, combined C2-phenylethynyl and N-6-2-phenylethyl substitutions in selective antagonist 15 provided a K-i of 20 nM. Differences between 4'-truncated and nontruncated analogues of extended C2-p-biphenylethynyl substitution suggested a ligand reorientation in AR binding, dominated by bulky N-6 groups in analogues lacking a stabilizing S'-uronamide moiety. Thus, 4'-truncation of C2-arylethynyl-(N)-methanocarba adenosine derivatives is compatible with general preservation of A(3)AR selectivity, especially with small N-6 groups, but reduced efficacy in A(3)AR-induced inhibition of adenylate cyclase.