2-(3''-(6''-bromo-1''-N-indolyl)ethyloxy)-6-(4-carboxylmethoxy)phenylamino-3',4',5'-triacetyladenosine | 1019779-13-5

• 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''-N-indolyl)ethyloxy)-6-(4-carboxylmethoxy)phenylamino-3',4',5'-triacetyladenosine
• 英文别名: 2-[4-[[2-[2-(6-bromo-1H-indol-3-yl)ethoxy]-9-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]purin-6-yl]amino]phenoxy]acetic acid
• CAS: 1019779-13-5
• 化学式: C₂₈H₂₇BrN₆O₈
• 分子量: 655.462
• InChiKey: RGQRUTDPGFBCJO-ZCIWVVNKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  43
• 可旋转键数：
  11
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  197
• 氢给体数：
  6
• 氢受体数：
  12

反应信息

• 作为反应物：
  描述：

  2-(3''-(6''-bromo-1''-N-indolyl)ethyloxy)-6-(4-carboxylmethoxy)phenylamino-3',4',5'-triacetyladenosine 、 benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 、 苯胺 在 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 18.5h， 以40%的产率得到MRS5099
  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：

  2-(3''-(6''-bromo-1''-(p-toluenesulfonyl)indolyl)ethyloxy)-6-(4-((phenylcarbamoyl)methoxy)phenylamino)-3',4',5,'-triacetyladenosine 在 氢氧化钾 作用下， 以 甲醇 为溶剂， 反应 18.0h， 以51%的产率得到2-(3''-(6''-bromo-1''-N-indolyl)ethyloxy)-6-(4-carboxylmethoxy)phenylamino-3',4',5'-triacetyladenosine
  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

文献信息

• Probing Distal Regions of the A_2B Adenosine Receptor by Quantitative Structure−Activity Relationship Modeling of Known and Novel Agonists
  作者：Andrei A. Ivanov、Ben Wang、Athena M. Klutz、Vincent L. Chen、Zhan-Guo Gao、Kenneth A. Jacobson

  DOI：10.1021/jm701442d

  日期：2008.4.1

  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.