5-methoxy-2-methyl-3-(p-toluenesulfonyloxyethyl)-1-(p-toluenesulfonyl)indole | 1026166-41-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 5-methoxy-2-methyl-3-(p-toluenesulfonyloxyethyl)-1-(p-toluenesulfonyl)indole
• 英文别名: 2-[5-Methoxy-2-methyl-1-(4-methylphenyl)sulfonylindol-3-yl]ethyl 4-methylbenzenesulfonate
• CAS: 1026166-41-5
• 化学式: C₂₆H₂₇NO₆S₂
• 分子量: 513.635
• InChiKey: MPDYVWNQDAYFTB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.6
• 重原子数：
  35
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  108
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  5-methoxy-2-methyl-3-(p-toluenesulfonyloxyethyl)-1-(p-toluenesulfonyl)indole 在 caesium carbonate 、 sodium iodide 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 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
• 作为产物：
  描述：

  5-甲氧基-2-甲基-3-吲哚乙酸 在 lithium aluminium tetrahydride 、 sodium hydride 、 对甲苯磺酸 作用下， 以 四氢呋喃 为溶剂， 反应 3.0h， 生成 5-methoxy-2-methyl-3-(p-toluenesulfonyloxyethyl)-1-(p-toluenesulfonyl)indole
  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

文献信息

• [EN] A2 ADENOSINE RECEPTOR AGONISTS<br/>[FR] AGONISTES DES RÉCEPTEURS D'ADÉNOSINE A2
  申请人：US GOV HEALTH & HUMAN SERV

  公开号：WO2009006089A2

  公开（公告）日：2009-01-08

  Disclosed are AZB adenosine receptor (AR) agonists of formula (I), in which R1, R2, R3, R4, Z, and n are defined herein. The invention also provides compositions comprising at least one compound of formula I and methods of use thereof, for example, in the treatment of septic shock, cystic fibrosis, restenosis, erectile dysfunction, inflammation, myocardial ischemia, and reperfusion injury.
• Structure−Activity Relationships of 2,<i>N</i>⁶,5‘-Substituted Adenosine Derivatives with Potent Activity at the A_2B Adenosine Receptor
  作者：Hayamitsu Adachi、Krishnan K. Palaniappan、Andrei A. Ivanov、Nathaniel Bergman、Zhan-Guo Gao、Kenneth A. Jacobson

  DOI：10.1021/jm061278q

  日期：2007.4.1

  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.