ethyl 4-[6-amino-8-(3-fluorophenyl)-2-[2-(1-hydroxycyclohexyl)-1-ethynyl]-9H-9-purinyl]benzoate | 391249-40-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: ethyl 4-[6-amino-8-(3-fluorophenyl)-2-[2-(1-hydroxycyclohexyl)-1-ethynyl]-9H-9-purinyl]benzoate
• CAS: 391249-40-4
• 化学式: C₂₈H₂₆FN₅O₃
• 分子量: 499.545
• InChiKey: CRKPFRNVVFSYQI-UHFFFAOYSA-N

物化性质

• 沸点：
  758.8±70.0 °C(Predicted)
• 密度：
  1.34±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.43
• 重原子数：
  37.0
• 可旋转键数：
  4.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  116.15
• 氢给体数：
  2.0
• 氢受体数：
  8.0

反应信息

• 作为反应物：
  描述：

  ethyl 4-[6-amino-8-(3-fluorophenyl)-2-[2-(1-hydroxycyclohexyl)-1-ethynyl]-9H-9-purinyl]benzoate 在 sodium hydroxide 作用下， 以 甲醇 、 氯仿 为溶剂， 以93%的产率得到4-[6-amino-8-(3-fluorophenyl)-2-[2-(1-hydroxycyclohexyl)-1-ethynyl]-9H-9-purinyl]benzoic acid
  参考文献：
  名称：

  2-Alkynyl-8-aryladenines possessing an amide moiety: their synthesis and structure–activity relationships of effects on hepatic glucose production induced via agonism of the A2B adenosine receptor

  摘要：

  A series of 2-alkynyl-8-aryladenine derivatives bearing an amide moiety at the 9-position of adenine was synthesized. These analogues were evaluated for inhibitory activity on N-ethylcarboxamidoadenosine (NECA)-induced glucose production in primary cultured rat hepatocytes. The in-primary benzamide derivative 15f was the most potent compound (IC50 = 0.017 PM), being 15-fold more active than the corresponding 9-methyl derivative (1). Compound 15f showed 72- and 5.2-fold selectivity for human A(2B) receptor versus human A(1) and A(2A) receptors, respectively. Structure-activity relationship (SAR) studies of the synthesized compounds indicated that a three-carbon linker, fixed in the form of a benzene ring, between the adenine core and the amide moiety is important for both A(2B) antagonistic activity and selectivity, The IC50 values in rat hepatocyte glucose assay correlated well with the IC50 values in cAMP assay using Chinese hamster ovary cells stably transfected with human A(2B) receptors (r(2) = 0.94). The A(1) and A(2A) affinities showed no correlation with the potency to inhibit NECA-induced glucose production. These results strongly support our previous conclusion that adenosine agonist-induced hepatic glucose production in rat hepatocytes is mediated through the A(2B) receptor. (C) 2001 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(01)00201-2
• 作为产物：
  描述：

  ethyl 4-[[2-(acetylamino)-5-nitro-6-oxo-1,6-dihydro-4-pyrimidinyl]amino]benzoate 在 bis-triphenylphosphine-palladium(II) chloride 、 sodium tetrahydroborate 、 copper(l) iodide 、 二碘甲烷 、 四乙基氯化铵 、 氨 、 溶剂黄146 、 N,N-二甲基苯胺 、 三乙胺 、 tin(ll) chloride 、 三氯氧磷 、 亚硝酸异戊酯 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 乙腈 为溶剂， 反应 2.0h， 生成 ethyl 4-[6-amino-8-(3-fluorophenyl)-2-[2-(1-hydroxycyclohexyl)-1-ethynyl]-9H-9-purinyl]benzoate
  参考文献：
  名称：

  2-Alkynyl-8-aryladenines possessing an amide moiety: their synthesis and structure–activity relationships of effects on hepatic glucose production induced via agonism of the A2B adenosine receptor

  摘要：

  A series of 2-alkynyl-8-aryladenine derivatives bearing an amide moiety at the 9-position of adenine was synthesized. These analogues were evaluated for inhibitory activity on N-ethylcarboxamidoadenosine (NECA)-induced glucose production in primary cultured rat hepatocytes. The in-primary benzamide derivative 15f was the most potent compound (IC50 = 0.017 PM), being 15-fold more active than the corresponding 9-methyl derivative (1). Compound 15f showed 72- and 5.2-fold selectivity for human A(2B) receptor versus human A(1) and A(2A) receptors, respectively. Structure-activity relationship (SAR) studies of the synthesized compounds indicated that a three-carbon linker, fixed in the form of a benzene ring, between the adenine core and the amide moiety is important for both A(2B) antagonistic activity and selectivity, The IC50 values in rat hepatocyte glucose assay correlated well with the IC50 values in cAMP assay using Chinese hamster ovary cells stably transfected with human A(2B) receptors (r(2) = 0.94). The A(1) and A(2A) affinities showed no correlation with the potency to inhibit NECA-induced glucose production. These results strongly support our previous conclusion that adenosine agonist-induced hepatic glucose production in rat hepatocytes is mediated through the A(2B) receptor. (C) 2001 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(01)00201-2