(1R,2R,3S,4R,5S)-4-(6-(3-bromobenzylamino)-2-(hex-1-ynyl)-9H-purin-9-yl)bicyclo[3.1.0]hexane-2,3-diol | 1546958-17-1

• 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-bromobenzylamino)-2-(hex-1-ynyl)-9H-purin-9-yl)bicyclo[3.1.0]hexane-2,3-diol
• 英文别名: (1R,2R,3S,4R,5S)-4-[6-[(3-bromophenyl)methylamino]-2-hex-1-ynylpurin-9-yl]bicyclo[3.1.0]hexane-2,3-diol
• CAS: 1546958-17-1
• 化学式: C₂₄H₂₆BrN₅O₂
• 分子量: 496.407
• InChiKey: VBJPKQZXOYDKPZ-RNPPMORTSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  32
• 可旋转键数：
  7
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.46
• 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：

  (3AS,4S,6AR)-2,2-二甲基-3A,6A-二氢-4H-环戊[D][1,3]二噁酚-4-醇 在 盐酸 、 copper(l) iodide 、 二碘甲烷 、 偶氮二甲酸二异丙酯 、 2,2,6,6-tetramethylpiperidinyl-lithium 、 diethylzinc 、 三乙胺 、 三苯基膦 作用下， 以 四氢呋喃 、 乙醇 、 正己烷 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 23.75h， 生成 (1R,2R,3S,4R,5S)-4-(6-(3-bromobenzylamino)-2-(hex-1-ynyl)-9H-purin-9-yl)bicyclo[3.1.0]hexane-2,3-diol
  参考文献：
  名称：

  Synthesis and Anti-Renal Fibrosis Activity of Conformationally Locked Truncated 2-Hexynyl-N⁶-Substituted-(N)-Methanocarba-nucleosides as A₃ Adenosine Receptor Antagonists and Partial Agonists

  摘要：

  Truncated N-6-substituted-(N)-methanocarba-adenosine derivatives with 2-hexynyl substitution were synthesized to examine parallels with corresponding 4'-thioadenosines. Hydrophobic N-6 and/or C2 substituents were tolerated in A(3)AR binding, but only an unsubstituted 6-amino group with a C2-hexynyl group promoted high hA(2A)AR affinity. A small hydrophobic alkyl (4b and 4c) or N-6-cycloalkyl group (4d) showed excellent binding affinity at the hA(3)AR and was better than an unsubstituted free amino group (4a). A(3)AR affinities of 3-halobenzylamine derivatives 4f-4i did not differ significantly, with K-i values of 7.8-16.0 nM. N-6-Methyl derivative 4b (K-i = 4.9 nM) was a highly selective, low efficacy partial A(3)AR agonist. All compounds were screened for renoprotective effects in human TGF-beta 1-stimulated mProx tubular cells, a kidney fibrosis model. Most compounds strongly inhibited TGF-beta 1-induced collagen I upregulation, and their A(3)AR binding affinities were proportional to antifibrotic effects; 4b was most potent (IC50 = 0.83 mu M), indicating its potential as a good therapeutic candidate for treating renal fibrosis.

  DOI：

  10.1021/jm4015313