2-(4-Amino-phenyl)-N-(9-chloro-2-furan-2-yl-[1,2,4]triazolo[1,5-c]quinazolin-5-yl)-acetamide | 210991-27-8

• 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: 2-(4-Amino-phenyl)-N-(9-chloro-2-furan-2-yl-[1,2,4]triazolo[1,5-c]quinazolin-5-yl)-acetamide
• 英文别名: 2-(4-aminophenyl)-N-[9-chloro-2-(furan-2-yl)-[1,2,4]triazolo[1,5-c]quinazolin-5-yl]acetamide
• CAS: 210991-27-8
• 化学式: C₂₁H₁₅ClN₆O₂
• 分子量: 418.842
• InChiKey: QQZIXJZPJJNMPH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  30
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.05
• 拓扑面积：
  111
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  2-(4-Amino-phenyl)-N-(9-chloro-2-furan-2-yl-[1,2,4]triazolo[1,5-c]quinazolin-5-yl)-acetamide 在 碘 、 calcium carbonate 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 12.0h， 以25%的产率得到2-(4-Amino-3-iodo-phenyl)-N-(9-chloro-2-furan-2-yl-[1,2,4]triazolo[1,5-c]quinazolin-5-yl)-acetamide
  参考文献：
  名称：

  Derivatives of the Triazoloquinazoline Adenosine Antagonist (CGS 15943) Having High Potency at the Human A_2B and A₃ Receptor Subtypes

  摘要：

  The adenosine antagonist 9-chloro-2-(2-furanyl)[1,2,4]triazolo[1,5-c]quinazolin-5-amine (CGS 15943) binds nonselectively to human A(1), A(2A), and A(3) receptors with high affinity. Acylated derivatives and one alkyl derivative of the 5-amino group and other modifications were prepared in an effort to enhance A(2B) or A(3) subtype potency. In general, distal modifications of the N-5-substituent were highly modulatory to potency and selectivity at adenosine receptors, as determined in radioligand binding assays at rat brain A(1) and A(2A) receptors and at recombinant human A(3) receptors. In Chinese hamster ovary cells stably transfected with human A(2B) receptor cDNA, inhibition of agonist-induced cyclic AMP production was measured. An N-5-(2-iodophenyl)acetyl derivative was highly selective for A(2A) receptors. An (R)-N-5-alpha-methyl-(phenylacetyl) derivative was the most potent derivative at A(3) receptors, with a K-i value of 0.36 nM. A bulky N-5-diphenylacetyl derivative, 13, displayed a K-i value of 0.59 nM at human A(3) receptors and was moderately selective for that subtype. Thus, a large, nondiscriminating hydrophobic region occurs in the Ag receptor in proximity to the N-5-substituent. A series of straight-chain N-5-aminoalkylacyl derivatives demonstrated that for A(2B) receptors the optimal chain length occurs with three methylene groups, i.e., the N-5-gamma-aminobutyryl derivative 27 which had a pA(2) value of 8.0 but was not selective for A(2B) receptors. At A(1), A(2A), and A(3) receptors however the optimum occurs with four methylene groups. An N-5-pivaloyl derivative, which was less potent than 27 at A(1), A(2A), and A(3) receptors, retained moderate potency at A(2B) receptors. A molecular model of the 27-A(2B) receptor complex based on the structure of rhodopsin utilizing a "cross-docking" procedure was developed in order to visualize the environment of the ligand binding site.

  DOI：

  10.1021/jm980094b
• 作为产物：
  描述：

  2-(4-硝基苯基)乙酰氯 在 platinum(IV) oxide 吡啶 、 氢气 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 27.0h， 生成 2-(4-Amino-phenyl)-N-(9-chloro-2-furan-2-yl-[1,2,4]triazolo[1,5-c]quinazolin-5-yl)-acetamide
  参考文献：
  名称：

  Derivatives of the Triazoloquinazoline Adenosine Antagonist (CGS 15943) Having High Potency at the Human A_2B and A₃ Receptor Subtypes

  摘要：

  The adenosine antagonist 9-chloro-2-(2-furanyl)[1,2,4]triazolo[1,5-c]quinazolin-5-amine (CGS 15943) binds nonselectively to human A(1), A(2A), and A(3) receptors with high affinity. Acylated derivatives and one alkyl derivative of the 5-amino group and other modifications were prepared in an effort to enhance A(2B) or A(3) subtype potency. In general, distal modifications of the N-5-substituent were highly modulatory to potency and selectivity at adenosine receptors, as determined in radioligand binding assays at rat brain A(1) and A(2A) receptors and at recombinant human A(3) receptors. In Chinese hamster ovary cells stably transfected with human A(2B) receptor cDNA, inhibition of agonist-induced cyclic AMP production was measured. An N-5-(2-iodophenyl)acetyl derivative was highly selective for A(2A) receptors. An (R)-N-5-alpha-methyl-(phenylacetyl) derivative was the most potent derivative at A(3) receptors, with a K-i value of 0.36 nM. A bulky N-5-diphenylacetyl derivative, 13, displayed a K-i value of 0.59 nM at human A(3) receptors and was moderately selective for that subtype. Thus, a large, nondiscriminating hydrophobic region occurs in the Ag receptor in proximity to the N-5-substituent. A series of straight-chain N-5-aminoalkylacyl derivatives demonstrated that for A(2B) receptors the optimal chain length occurs with three methylene groups, i.e., the N-5-gamma-aminobutyryl derivative 27 which had a pA(2) value of 8.0 but was not selective for A(2B) receptors. At A(1), A(2A), and A(3) receptors however the optimum occurs with four methylene groups. An N-5-pivaloyl derivative, which was less potent than 27 at A(1), A(2A), and A(3) receptors, retained moderate potency at A(2B) receptors. A molecular model of the 27-A(2B) receptor complex based on the structure of rhodopsin utilizing a "cross-docking" procedure was developed in order to visualize the environment of the ligand binding site.

  DOI：

  10.1021/jm980094b

文献信息

• Derivatives of the Triazoloquinazoline Adenosine Antagonist (CGS 15943) Having High Potency at the Human A_2B and A₃ Receptor Subtypes
  作者：Yong-Chul Kim、Maarten de Zwart、Louis Chang、Stefano Moro、Jacobien K. von Frijtag Drabbe Künzel、Neli Melman、Ad P. IJzerman、Kenneth A. Jacobson

  DOI：10.1021/jm980094b

  日期：1998.7.1

  The adenosine antagonist 9-chloro-2-(2-furanyl)[1,2,4]triazolo[1,5-c]quinazolin-5-amine (CGS 15943) binds nonselectively to human A(1), A(2A), and A(3) receptors with high affinity. Acylated derivatives and one alkyl derivative of the 5-amino group and other modifications were prepared in an effort to enhance A(2B) or A(3) subtype potency. In general, distal modifications of the N-5-substituent were highly modulatory to potency and selectivity at adenosine receptors, as determined in radioligand binding assays at rat brain A(1) and A(2A) receptors and at recombinant human A(3) receptors. In Chinese hamster ovary cells stably transfected with human A(2B) receptor cDNA, inhibition of agonist-induced cyclic AMP production was measured. An N-5-(2-iodophenyl)acetyl derivative was highly selective for A(2A) receptors. An (R)-N-5-alpha-methyl-(phenylacetyl) derivative was the most potent derivative at A(3) receptors, with a K-i value of 0.36 nM. A bulky N-5-diphenylacetyl derivative, 13, displayed a K-i value of 0.59 nM at human A(3) receptors and was moderately selective for that subtype. Thus, a large, nondiscriminating hydrophobic region occurs in the Ag receptor in proximity to the N-5-substituent. A series of straight-chain N-5-aminoalkylacyl derivatives demonstrated that for A(2B) receptors the optimal chain length occurs with three methylene groups, i.e., the N-5-gamma-aminobutyryl derivative 27 which had a pA(2) value of 8.0 but was not selective for A(2B) receptors. At A(1), A(2A), and A(3) receptors however the optimum occurs with four methylene groups. An N-5-pivaloyl derivative, which was less potent than 27 at A(1), A(2A), and A(3) receptors, retained moderate potency at A(2B) receptors. A molecular model of the 27-A(2B) receptor complex based on the structure of rhodopsin utilizing a "cross-docking" procedure was developed in order to visualize the environment of the ligand binding site.