6-chloro-2-(3''-(5''-methoxy-2''-methyl-1''-(p-toluenesulfonyl)indolyl)ethyloxy)-3',4',5'-triacetyladenosine | 936252-78-7

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物
• 英文名称: 6-chloro-2-(3''-(5''-methoxy-2''-methyl-1''-(p-toluenesulfonyl)indolyl)ethyloxy)-3',4',5'-triacetyladenosine
• 英文别名: 6-chloro-2-(3"-(5"-methoxy-2"-methyl-1"-(p-toluenesulfonyl)indolyl)ethyloxy)-3',4',5'-triacetyladenosine；[(2R,3R,4R,5R)-3,4-diacetyloxy-5-[6-chloro-2-[2-[5-methoxy-2-methyl-1-(4-methylphenyl)sulfonylindol-3-yl]ethoxy]purin-9-yl]oxolan-2-yl]methyl acetate
• CAS: 936252-78-7
• 化学式: C₃₅H₃₆ClN₅O₁₁S
• 分子量: 770.217
• InChiKey: KHVWEOVXWVMXMN-UTBAFCPYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  53
• 可旋转键数：
  15
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.37
• 拓扑面积：
  198
• 氢给体数：
  0
• 氢受体数：
  14

反应信息

• 作为反应物：
  描述：

  6-chloro-2-(3''-(5''-methoxy-2''-methyl-1''-(p-toluenesulfonyl)indolyl)ethyloxy)-3',4',5'-triacetyladenosine 在 氨 作用下， 以 乙醇 为溶剂， 以71%的产率得到2-(3"-(5"-methoxy-2"-methyl-1"-(p-toluenesulfonyl)indolyl)ethyloxy)adenosine
  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
• 作为产物：
  描述：

  5-甲氧基-2-甲基-3-吲哚乙酸 在 lithium aluminium tetrahydride 、 sodium hydride 、 caesium carbonate 、 对甲苯磺酸 、 sodium iodide 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 3.0h， 生成 6-chloro-2-(3''-(5''-methoxy-2''-methyl-1''-(p-toluenesulfonyl)indolyl)ethyloxy)-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