(1'S,2'R,3'S,4'R,5'S)-4-(6-amino-9H-purin-9-yl)-1-[hydroxymethyl]bicyclo[3.1.0]hexane-2,3-(O-isopropylidene) | 174498-04-5

• 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: (1'S,2'R,3'S,4'R,5'S)-4-(6-amino-9H-purin-9-yl)-1-[hydroxymethyl]bicyclo[3.1.0]hexane-2,3-(O-isopropylidene)
• 英文别名: ((3aR,3bR,4aS,5R,5aS)-5-(6-amino-9H-purin-9-yl)-2,2-dimethyltetrahydrocyclopropa- [3,4]cyclopenta[1,2-d][1,3]dioxol-3b(3aH)-yl)methanol；(1'R,2'R,3'S,4'R,5'S)-4-(6-aminopurine-9-yl)-1-[hydroxymethyl]bicyclo[3.1.0]hexane-2,3-(O-isopropylidine)
• CAS: 174498-04-5
• 化学式: C₁₅H₁₉N₅O₃
• 分子量: 317.348
• InChiKey: UXXBUEVSCRXTKE-LCNRAPRPSA-N

物化性质

• 沸点：
  562.1±60.0 °C(Predicted)
• 密度：
  1.83±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.48
• 重原子数：
  23.0
• 可旋转键数：
  2.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  108.31
• 氢给体数：
  2.0
• 氢受体数：
  8.0

反应信息

• 作为反应物：
  描述：

  (1'S,2'R,3'S,4'R,5'S)-4-(6-amino-9H-purin-9-yl)-1-[hydroxymethyl]bicyclo[3.1.0]hexane-2,3-(O-isopropylidene) 在 2,2,6,6-四甲基哌啶氧化物 、 碘苯二乙酸 、 N,N-二异丙基乙胺 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 作用下， 以 水 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 生成 (3aR,3bS,4aS,5R,5aS)-5-(6-amino-9H-purin-9-yl)-N-(2,2-difluoroethyl)-2,2-dimethyltetrahydrocyclopropa[3,4]cyclopenta[1,2-d][1,3]dioxole-3b(3aH)-carboxamide
  参考文献：
  名称：

  Biological Evaluation of 5′-(N-Ethylcarboxamido)adenosine Analogues as Grp94-Selective Inhibitors

  摘要：

  DOI：

  10.1021/acsmedchemlett.0c00509
• 作为产物：
  描述：

  9-((3aR,3bR,4aS,5R,5aS)-3b-(((tert-butyldiphenylsilyl)oxy)methyl)-2,2-dimethylhexahydrocyclopropa[3,4]cyclopenta[1,2-d][1,3]dioxol-5-yl)-6-chloro-9H-purine 在 四丁基氟化铵 、 氨 作用下， 以 四氢呋喃 、 异丙醇 为溶剂， 反应 1.0h， 生成 (1'S,2'R,3'S,4'R,5'S)-4-(6-amino-9H-purin-9-yl)-1-[hydroxymethyl]bicyclo[3.1.0]hexane-2,3-(O-isopropylidene)
  参考文献：
  名称：

  Biological Evaluation of 5′-(N-Ethylcarboxamido)adenosine Analogues as Grp94-Selective Inhibitors

  摘要：

  DOI：

  10.1021/acsmedchemlett.0c00509

文献信息

• Methanocarba Modification of Uracil and Adenine Nucleotides:  High Potency of Northern Ring Conformation at P2Y₁, P2Y₂, P2Y₄, and P2Y₁₁ but Not P2Y₆ Receptors
  作者：Hak Sung Kim、R. Gnana Ravi、Victor E. Marquez、Savitri Maddileti、Anna-Karin Wihlborg、David Erlinge、Malin Malmsjö、José L. Boyer、T. Kendall Harden、Kenneth A. Jacobson

  DOI：10.1021/jm010369e

  日期：2002.1.1

  The potency of nucleotide antagonists at P2Y(1) receptors was enhanced by replacing the ribose moiety with a constrained carbocyclic ring (Nandanan, et al. J. Med. Chem. 2000, 43, 829842). We have now synthesized ring-constrained methanocarba analogues (in which a fused cyclopropane moiety constrains the pseudosugar ring) of adenine and uracil nucleotides, the endogenous activators of P2Y receptors. Methanocarba-adenosine 5'-triphosphate (ATP) was fixed in either a Northern (N) or a Southern (S) conformation, as defined in the pseudorotational cycle. (N)-Methanocarba-uridine was prepared from the 1-amino-pseudosugar ring by treatment with beta-ethoxyacryloyl cyanate and cyclization to form the uracil ring. Phosphorylation was carried out at the 5'-hydroxyl group through a multistep process: Reaction with phosphoramidite followed by oxidation provided the 5'-monophosphates, which then were treated with 1,1'-carbonyldiimidazole for condensation with additional phosphate groups, The ability of the analogues to stimulate phospholipase C through activation of turkey P2Y(1) or human P2Y(1), P2Y(2), P2Y(4), P2Y(6), and P2Y(11) receptors stably expressed in astrocytoma cells was measured. At recombinant human P2Y(1) and P2Y(2) receptors, (N)-methanocarba-ATP was 138- and 41-fold, respectively, more potent than racemic (S)-methanocarba-ATP as an agonist. (N)methanocarba-ATP activated P2Y(11) receptors with a potency similar to ATP. (N)-Methanocarba-uridine 5'-triphosphate (UTP) was equipotent to UTP as an agonist at human P2Y2 receptors and also activated P2Y(4) receptors with an EC50 of 85 nM. (N)-Methanocarba-uridine 5'-diphosphate (UDP) was inactive at the hP2Y(6) receptor. The vascular effects of (N)-methanocarba-UTP and (N)-methanocarba-UDP were studied in a model of the rat mesenteric artery, The triphosphate was more potent than UTP in inducing a dilatory P2Y(4) response (pEC(50) = 6.1 +/- 0.2), while the diphosphate was inactive as either an agonist or antagonist in a P2Y(6) receptor-mediated contractile response. Our results suggest that new nucleotide agonists may be designed on the basis of the (N) conformation that favors selectivity for P2Y(1), P2Y(2), P2Y(4), and P2Y(11) receptors.
• Jeong, Lak S.; Marquez, Victor E.; Yuan, Chong-Shen, Heterocycles, 1995, vol. 41, # 12, p. 2651 - 2656
  作者：Jeong, Lak S.、Marquez, Victor E.、Yuan, Chong-Shen、Borchardt, Ronald T.

  DOI：——

  日期：——