7-(2-phenylethyl)-2-(4-chlorophenyl)pyrazolo[4,3-e]-1,2,4-triazolo[1,5-c]pyrimidine | 512844-84-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 7-(2-phenylethyl)-2-(4-chlorophenyl)pyrazolo[4,3-e]-1,2,4-triazolo[1,5-c]pyrimidine
• 英文别名: 4-(4-chlorophenyl)-10-(2-phenylethyl)-3,5,6,8,10,11-hexazatricyclo[7.3.0.02,6]dodeca-1(9),2,4,7,11-pentaene
• CAS: 512844-84-7
• 化学式: C₂₀H₁₅ClN₆
• 分子量: 374.832
• InChiKey: AXBHLYBOAWHFIY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  27
• 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：

  7-(2-phenylethyl)-2-(4-chlorophenyl)pyrazolo[4,3-e]-1,2,4-triazolo[1,5-c]pyrimidine 在 盐酸 作用下， 以 1,4-二氧六环 为溶剂， 反应 0.75h， 以90%的产率得到5-amino-1-(2-phenylethyl)-4-[3-(4-chlorophenyl)-1,2,4-triazolo-5-yl]pyrazole
  参考文献：
  名称：

  作为新的A2A和A3腺苷受体拮抗剂的C9和C2取代的吡唑并[4,3-e] -1,2,4-三唑并[1,5-c]嘧啶的设计，合成和生物学评估。

  摘要：

  在过去的几年中，我们小组一直致力于A（2A）和A（3）腺苷受体拮抗剂的开发，从而导致了SCH58261（5-氨基-7-（2-苯乙基）-2-（ 2-furyl）pyrazolo [4,3-e] -1,2,4-triazolo [1,5-c] pyrimi dine，61），对A（2A）受体亚型和N（8 ）-取代的吡唑并[4,3-e] -1,2,4-三唑并[1,5-c]嘧啶-N（5）-脲或酰胺（MRE系列，b），对人A的选择性很高（3）腺苷受体亚型。我们现在描述一系列由C（9）-和C（2）取代的吡唑并[4,3-e] -1,2,4-三唑并[1,5-c]嘧啶，以代表结构的扩展-这类三环化合物之间存在活性关系。在三环拮抗结构的9位上引入取代基导致保留受体亲和力，但相对于先导化合物b，N（8）-取代的吡唑并[4,3-e] -1，失去了选择性， 2,4-三唑并[1,5-c]嘧啶-N（5）-脲或-酰胺。受

  DOI：

  10.1021/jm021023m
• 作为产物：
  描述：

  5-amino-4-cyano-1-(β-phenylethyl)pyrazole 以 二苯醚 、 乙二醇甲醚 为溶剂， 反应 13.5h， 生成 7-(2-phenylethyl)-2-(4-chlorophenyl)pyrazolo[4,3-e]-1,2,4-triazolo[1,5-c]pyrimidine
  参考文献：
  名称：

  作为新的A2A和A3腺苷受体拮抗剂的C9和C2取代的吡唑并[4,3-e] -1,2,4-三唑并[1,5-c]嘧啶的设计，合成和生物学评估。

  摘要：

  在过去的几年中，我们小组一直致力于A（2A）和A（3）腺苷受体拮抗剂的开发，从而导致了SCH58261（5-氨基-7-（2-苯乙基）-2-（ 2-furyl）pyrazolo [4,3-e] -1,2,4-triazolo [1,5-c] pyrimi dine，61），对A（2A）受体亚型和N（8 ）-取代的吡唑并[4,3-e] -1,2,4-三唑并[1,5-c]嘧啶-N（5）-脲或酰胺（MRE系列，b），对人A的选择性很高（3）腺苷受体亚型。我们现在描述一系列由C（9）-和C（2）取代的吡唑并[4,3-e] -1,2,4-三唑并[1,5-c]嘧啶，以代表结构的扩展-这类三环化合物之间存在活性关系。在三环拮抗结构的9位上引入取代基导致保留受体亲和力，但相对于先导化合物b，N（8）-取代的吡唑并[4,3-e] -1，失去了选择性， 2,4-三唑并[1,5-c]嘧啶-N（5）-脲或-酰胺。受

  DOI：

  10.1021/jm021023m

文献信息

• 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?
  作者：Siew Lee Cheong、Anton V. Dolzhenko、Silvia Paoletta、Evelyn Pei Rong Lee、Sonja Kachler、Stephanie Federico、Karl-Norbert Klotz、Anna V. Dolzhenko、Giampiero Spalluto、Stefano Moro、Giorgia Pastorin

  DOI：10.1016/j.bmc.2011.08.026

  日期：2011.10

  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.
• 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.
• PHARMACEUTICALLY ACTIVE COMPOUNDS HAVING A TRICYCLIC PYRAZOLOTRIAZOLOPYRIMIDINE RING STRUCTURE AND METHODS OF USE
  申请人：King Pharmaceuticals Research and Development Inc.

  公开号：EP1549319A2

  公开（公告）日：2005-07-06
• [EN] PHARMACEUTICALLY ACTIVE COMPOUNDS HAVING A TRICYCLIC PYRAZOLOTRIAZOLOPYRIMIDINE RING STRUCTURE AND METHODS OF USE<br/>[FR] COMPOSES PHARMACEUTIQUEMENT ACTIFS A STRUCTURE CYCLIQUE PYRAZOLOTRIAZOLOPYRIMIDINE TRICYCLIQUE ET PROCEDES D'UTILISATION DE CEUX-CI
  申请人：KING PHARMACEUTICALS RES & DEV

  公开号：WO2003101455A2

  公开（公告）日：2003-12-11

  New compounds having a tricyclic pyrazolotriazolopyrimidine ring structure are provided and methods of using those compounds for a variety of therapeutic indications, based on their affinity at adenosine receptors.