ethyl 4,5-dihydro-4-oxo-8-chloro-1,2,4-triazolo<1,5-a>quinoxaline-2-carboxylate | 155951-38-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: ethyl 4,5-dihydro-4-oxo-8-chloro-1,2,4-triazolo<1,5-a>quinoxaline-2-carboxylate
• 英文别名: ethyl 8-chloro-4,5-dihydro-4-oxo-1,2,4-triazolo[1,5-a]quinoxalin-2-carboxylate；ethyl 8-chloro-4-oxo-4,5-dihydro-[1,2,4]triazolo[1,5-a]quinoxaline-2-carboxylate；ethyl 8-chloro-4-oxo-5H-[1,2,4]triazolo[1,5-a]quinoxaline-2-carboxylate
• CAS: 155951-38-5
• 化学式: C₁₂H₉ClN₄O₃
• 分子量: 292.681
• InChiKey: BYSUTBXNUZIDGV-UHFFFAOYSA-N

物化性质

• 密度：
  1.67±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  20
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  86.1
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  ethyl 4,5-dihydro-4-oxo-8-chloro-1,2,4-triazolo<1,5-a>quinoxaline-2-carboxylate 在 五氯化磷 、 三氯氧磷 作用下， 反应 3.0h， 以85%的产率得到ethyl 4,8-dichloro-1,2,4-triazolo[1,5-a]quinoxalin-2-carboxylate
  参考文献：
  名称：

  1,2,4-三唑并[1,5-a]喹喔啉衍生物：腺苷受体拮抗剂的合成及生物学评价。

  摘要：

  由于大多数已报道的腺苷受体拮抗剂是2-（杂）芳基取代的三环杂芳族衍生物，因此在本研究中，我们报道了一组新的4-氨基-1,2,4-三唑并合成和生物学评估[在位置2处含有羧酸乙酯基团或氢原子的1，5-a]喹喔啉。这些化合物的结构活性关系与先前报道的一系列类似的大小和形状一致，因此表明了相似的A（1）结合模式。特别地，结合数据表明这些衍生物的4-氨基的烷基化导致有效的A（1）-受体拮抗剂。此外，作为新的结果，该研究指出，2-羧酸乙酯基团可以有利地取代先前报道的三唑并喹喔啉衍生物的2-（杂）芳基环，

  DOI：

  10.1016/j.farmac.2003.09.005
• 作为产物：
  描述：

  ethyl N¹-(2-nitro-5-chlorophenyl)hydrazono-N²-chloroacetate 在 氨 、 铁粉 、 溶剂黄146 作用下， 以 1,4-二氧六环 、 乙醚 为溶剂， 生成 ethyl 4,5-dihydro-4-oxo-8-chloro-1,2,4-triazolo<1,5-a>quinoxaline-2-carboxylate
  参考文献：
  名称：

  1,2,4-Triazolo[1,5-a]quinoxaline as a Versatile Tool for the Design of Selective Human A₃ Adenosine Receptor Antagonists:  Synthesis, Biological Evaluation, and Molecular Modeling Studies of 2-(Hetero)aryl- and 2-Carboxy-Substitued Derivatives

  摘要：

  A number of 4-oxo-substituted 1,2,4-triazolo[1,5-alquinoxaline derivatives bearing at position-2 the claimed (hetero)aryl moiety (compounds 1-15) but also a carboxylate group (16-28, 3236) or a hydrogen atom (29-31) were designed as human A(3) (hA(3)) adenosine receptor (AR) antagonists. This study produced some interesting compounds and among them the 2-(4methoxyphenyl)-1,2,4-triazolo[1,5-alquinoxalin-4-one (8), which can be considered one of the most potent and selective hA(3) adenosine receptor antagonists reported till now. Moreover, as a new finding, replacement of the classical 2-(hetero)aryl moiety with a 2-carboxylate function (compounds 16-28 and 32-36) maintained good hA(3) AR binding activity but, most importantly and interestingly, produced a large increase in bA(3) versus hA(1) selectivity. A receptor-based SAR analysis provided new interesting insights about the steric and electrostatic requirements that are important for the anchoring of these derivatives at the hA(3) receptor recognition site, thus highlighting the versatility of the triazoloquinoxaline scaffold for obtaining potent and selective hA(3) AR antagonists.

  DOI：

  10.1021/jm0504149

文献信息

• HETEROCYCLIC INHIBITORS OF HISTAMINE RECEPTORS FOR THE TREATMENT OF DISEASE
  申请人：Borchardt Allen J.

  公开号：US20100120741A1

  公开（公告）日：2010-05-13

  The present invention relates to compounds and methods which may be useful as inhibitors of H 1 R and/or H 4 R for the treatment or prevention of inflammatory, autoimmune, allergic, and ocular diseases.

  本发明涉及化合物和方法，这些化合物和方法可能用作H1R和/或H4R的抑制剂，用于治疗或预防炎症性、自身免疫性、过敏性和眼部疾病。
• Catarzi; Cecchi; Colotta, Il Farmaco, 1993, vol. 48, # 8, p. 1065 - 1078
  作者：Catarzi、Cecchi、Colotta、Melani、Filacchioni、Martini、Giusti、Lucacchini

  DOI：——

  日期：——
• [EN] HETEROCYCLIC INHIBITORS OF HISTAMINE RECEPTORS FOR THE TREATMENT OF DISEASE<br/>[FR] INHIBITEURS HÉTÉROCYCLIQUES DE RÉCEPTEURS DE L'HISTAMINE DESTINÉS AU TRAITEMENT DE MALADIE
  申请人：KALYPSYS INC

  公开号：WO2011112731A3

  公开（公告）日：2012-01-12
• [EN] HETEROCYCLIC INHIBITORS OF HISTAMINE RECEPTORS FOR THE TREATMENT OF DISEASE<br/>[FR] INHIBITEURS HÉTÉROCYLIQUES DES RÉCEPTEURS DE L'HISTAMINE DESTINÉS AU TRAITEMENT D'UNE MALADIE
  申请人：KALYPSYS INC

  公开号：WO2010030785A2

  公开（公告）日：2010-03-18

  The present invention relates to compounds and methods which may be useful as inhibitors of H1R and/or H4R for the treatment or prevention of inflammatory, autoimmune, allergic, and ocular diseases.
• 1,2,4-Triazolo[1,5-<i>a</i>]quinoxaline as a Versatile Tool for the Design of Selective Human A₃ Adenosine Receptor Antagonists:  Synthesis, Biological Evaluation, and Molecular Modeling Studies of 2-(Hetero)aryl- and 2-Carboxy-Substitued Derivatives
  作者：Daniela Catarzi、Vittoria Colotta、Flavia Varano、Ombretta Lenzi、Guido Filacchioni、Letizia Trincavelli、Claudia Martini、Christian Montopoli、Stefano Moro

  DOI：10.1021/jm0504149

  日期：2005.12.1

  A number of 4-oxo-substituted 1,2,4-triazolo[1,5-alquinoxaline derivatives bearing at position-2 the claimed (hetero)aryl moiety (compounds 1-15) but also a carboxylate group (16-28, 3236) or a hydrogen atom (29-31) were designed as human A(3) (hA(3)) adenosine receptor (AR) antagonists. This study produced some interesting compounds and among them the 2-(4methoxyphenyl)-1,2,4-triazolo[1,5-alquinoxalin-4-one (8), which can be considered one of the most potent and selective hA(3) adenosine receptor antagonists reported till now. Moreover, as a new finding, replacement of the classical 2-(hetero)aryl moiety with a 2-carboxylate function (compounds 16-28 and 32-36) maintained good hA(3) AR binding activity but, most importantly and interestingly, produced a large increase in bA(3) versus hA(1) selectivity. A receptor-based SAR analysis provided new interesting insights about the steric and electrostatic requirements that are important for the anchoring of these derivatives at the hA(3) receptor recognition site, thus highlighting the versatility of the triazoloquinoxaline scaffold for obtaining potent and selective hA(3) AR antagonists.