4-Phenyl-11-(2-phenylethyl)-3,5,6,8,10,11-hexazatricyclo[7.3.0.02,6]dodeca-1(12),2,4,7,9-pentaene | 1221500-14-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 4-Phenyl-11-(2-phenylethyl)-3,5,6,8,10,11-hexazatricyclo[7.3.0.02,6]dodeca-1(12),2,4,7,9-pentaene
• CAS: 1221500-14-6
• 化学式: C₂₀H₁₆N₆
• 分子量: 340.387
• InChiKey: YALNYFLLNQVNDW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  26
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  60.9
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-Phenyl-11-(2-phenylethyl)-3,5,6,8,10,11-hexazatricyclo[7.3.0.02,6]dodeca-1(12),2,4,7,9-pentaene 在 盐酸 、 对甲苯磺酸 、 N,N-二异丙基乙胺 作用下， 以 N-甲基吡咯烷酮 、 甲苯 为溶剂， 反应 24.0h， 生成 N-[2-(phenyl)-8-phenylethyl-pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidin-5-yl]phenylacetamide
  参考文献：
  名称：

  Does the combination of optimal substitutions at the C2-, N5- and N8-positions of the pyrazolo-triazolo-pyrimidine scaffold guarantee selective modulation of the human A3 adenosine receptors?

  摘要：

  In an attempt to study the optimal combination of a phenyl ring at the C-2-position and different substituents at the N-5- and N-8-positions towards the selective modulation of human A(3) adenosine receptors (hA(3)AR), we synthesized a new series of 2-para-(un)substituted-phenyl-pyrazolo-triazolo-pyrimidines bearing either a methyl or phenylethyl at N-8 and chains of variable length at N-5. Through biological evaluation, it was found that the majority of the compounds had good affinities towards the hA(3)AR in the low nanomolar range. Compound 16 possessed the best hA(3)AR affinity and selectivity profile (K(i)hA(3) = 1.33 nM; hA(1)/hA(3) = 4880; hA(2A)/hA(3) = 1100) in the present series of2-(substituted)phenylpyrazolo-triazolo-pyrimidine derivatives. In addition to pharmacological characterization, a molecular modeling investigation on these compounds further elucidated the effect of different substituents at the pyrazolo-triazolo-pyrimidine scaffold on affinity and selectivity to hA3AR. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.08.026
• 作为产物：
  描述：

  2-碘代乙基苯 、 苯甲酰肼 、 原甲酸三乙酯 、 3-氨基-4-氰基吡唑 在 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 4-Phenyl-11-(2-phenylethyl)-3,5,6,8,10,11-hexazatricyclo[7.3.0.02,6]dodeca-1(12),2,4,7,9-pentaene 、 7-(2-phenylethyl)-2-phenylpyrazolo[4,3-e]-1,2,4-triazolo[1,5-c]pyrimidine
  参考文献：
  名称：

  Does the combination of optimal substitutions at the C2-, N5- and N8-positions of the pyrazolo-triazolo-pyrimidine scaffold guarantee selective modulation of the human A3 adenosine receptors?

  摘要：

  In an attempt to study the optimal combination of a phenyl ring at the C-2-position and different substituents at the N-5- and N-8-positions towards the selective modulation of human A(3) adenosine receptors (hA(3)AR), we synthesized a new series of 2-para-(un)substituted-phenyl-pyrazolo-triazolo-pyrimidines bearing either a methyl or phenylethyl at N-8 and chains of variable length at N-5. Through biological evaluation, it was found that the majority of the compounds had good affinities towards the hA(3)AR in the low nanomolar range. Compound 16 possessed the best hA(3)AR affinity and selectivity profile (K(i)hA(3) = 1.33 nM; hA(1)/hA(3) = 4880; hA(2A)/hA(3) = 1100) in the present series of2-(substituted)phenylpyrazolo-triazolo-pyrimidine derivatives. In addition to pharmacological characterization, a molecular modeling investigation on these compounds further elucidated the effect of different substituents at the pyrazolo-triazolo-pyrimidine scaffold on affinity and selectivity to hA3AR. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.08.026

文献信息

• The Significance of 2-Furyl Ring Substitution with a 2-(<i>para</i>-substituted) Aryl Group in a New Series of Pyrazolo-triazolo-pyrimidines as Potent and Highly Selective hA₃ Adenosine Receptors Antagonists: New Insights into Structure−Affinity Relationship and Receptor−Antagonist Recognition
  作者：Siew Lee Cheong、Anna Dolzhenko、Sonja Kachler、Silvia Paoletta、Stephanie Federico、Barbara Cacciari、Anton Dolzhenko、Karl-Norbert Klotz、Stefano Moro、Giampiero Spalluto、Giorgia Pastorin

  DOI：10.1021/jm100049f

  日期：2010.4.22

  Among the heterocyclic structures identified as potent human A(3) (hA(3)) adenosine receptor's antagonists, we have demonstrated that the new pyrazolo-triazolo-pyrimidines, bearing an aryl group in replacement of the C-2-furyl ring, not only confer a good pharmacological profile (with significantly enhanced selectivity against other adenosine receptor subytpes) but also overcome the metabolic transformation of the furan ring into toxic intermediates. All the synthesized [2-(para-substituted) phenyl]-pyrazolo-triazolo-pyrimidines showed affinity at the hA(3) receptor in the low nanomolar range. The most potent derivative of the series presented better affinity and excellent selectivity (compound 31, K-i hA(3) = 0.108 nM; hA(1)/hA(3) = 5200; hA(2A)/hA(3) = 7200), in comparison to the C-2-furyl counterpart. A receptor-driven molecular modeling investigation, based on a recently proposed model of A(3) receptor derived from the crystallographic structure of human A(2A) receptor, has been carried out in order to support the experimental binding data and to justify the enhanced selectivity against the other receptor subtypes.