2-(3''-(6''-bromo-1''-(p-toluenesulfonyl)indolyl)ethyloxy)-6-chloro-3',4',5'-triacetyladenosine | 936252-80-1

• 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: 2-(3''-(6''-bromo-1''-(p-toluenesulfonyl)indolyl)ethyloxy)-6-chloro-3',4',5'-triacetyladenosine
• 英文别名: 2-(3"-(6"-bromo-1"-(p-toluenesulfonyl)indolyl)ethyloxy)-6-chloro-3',4',5'-triacetyladenosine；[(2R,3R,4R,5R)-3,4-diacetyloxy-5-[2-[2-[6-bromo-1-(4-methylphenyl)sulfonylindol-3-yl]ethoxy]-6-chloropurin-9-yl]oxolan-2-yl]methyl acetate
• CAS: 936252-80-1
• 化学式: C₃₃H₃₁BrClN₅O₁₀S
• 分子量: 805.06
• InChiKey: GQLVZOZXKXMOBS-DWCTZGTLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.2
• 重原子数：
  51
• 可旋转键数：
  14
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  188
• 氢给体数：
  0
• 氢受体数：
  13

反应信息

• 作为反应物：
  描述：

  2-(3''-(6''-bromo-1''-(p-toluenesulfonyl)indolyl)ethyloxy)-6-chloro-3',4',5'-triacetyladenosine 在 肼 作用下， 反应 48.0h， 以43%的产率得到MRS5098
  参考文献：
  名称：

  Probing Distal Regions of the A_2B Adenosine Receptor by Quantitative Structure−Activity Relationship Modeling of Known and Novel Agonists

  摘要：

  The binding modes at the A(2B) adenosine receptor (AR) of 72 derivatives of adenosine and its 5'-N-methyluronamide with diverse substitutions at the 2 and N-6 positions were studied using a molecular modeling approach. The compounds in their receptor-docked conformations were used to build CoMFA and CoMSIA quantitative structure-activity relationship models. Various parameters, including different types of atomic charges, were examined. The best statistical parameters were obtained with a joint CoMFA and CoMSIA model: R-2 = 0.960, Q(2) = 0.676, SEE = 0.175, F = 158, and R-test(2) = 0.782 for an independent test set containing 18 compounds. On the basis of the modeling results. four novel adenosine analogues, having elongated or bulky substitutions at N-6 position and/or 2 position, were synthesized and evaluated biologically. All of the proposed compounds were potent, full agonists at the A(2B) AR in adenylate cyclase studies. Thus, in support of the modeling, bulky substitutions at both positions did not prevent A(2B) AR activation, which predicts separate regions for docking of these moieties.

  DOI：

  10.1021/jm701442d
• 作为产物：
  描述：

  3-溴苯肼盐酸盐 在 sodium hydride 、 caesium carbonate 、 sodium iodide 作用下， 以 四氢呋喃 、 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 1.0h， 生成 2-(3''-(6''-bromo-1''-(p-toluenesulfonyl)indolyl)ethyloxy)-6-chloro-3',4',5'-triacetyladenosine
  参考文献：
  名称：

  Structure−Activity Relationships of 2,N⁶,5‘-Substituted Adenosine Derivatives with Potent Activity at the A_2B Adenosine Receptor

  摘要：

  2, N-6, and 5'-substituted adenosine derivatives were synthesized via alkylation of 2-oxypurine nucleosides leading to 2-arylalkylether derivatives. 2-(3-(Indolyl)ethyloxy)adenosine 17 was examined in both binding and cAMP assays and found to be a potent agonist of the human A(2B)AR. Simplification, altered connectivity, and mimicking of the indole ring of 17 failed to maintain A2BAR potency. Introduction of N-6-ethyl or N-6-guanidino substitution, shown to favor A2BAR potency, failed to enhance potency in the 2-( 3-( indolyl)ethyloxy) adenosine series. Indole 5 ''- or 6 ''-halo substitution was favored at the A(2B)AR, but a 5'-N-ethylcarboxyamide did not further enhance potency. 2-(3 ''-(6 ''-Bromoindolyl)ethyloxy)adenosine 28 displayed an A(2B)AR EC50 value of 128 nM, that is, more potent than the parent 17 (299 nM) and similar to 5'-N-ethylcarboxamidoadenosine (140 nM). Compound 28 was a full agonist at A(2B) and A(2A)ARs and a low efficacy partial agonist at A(1) and A(3)ARs. Thus, we have identified and optimized 2-(2-arylethyl) oxo moieties in AR agonists that enhance A(2B)AR potency and selectivity.

  DOI：

  10.1021/jm061278q