5-amino-7-[2-(2',4',5'-tribromo)phenylethyl]-2-(2-furyl)-pyrazolo[4,3-e]-1,2,4-triazolo[1,5-c]pyrimidine | 181622-20-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 三唑并嘧啶类
• 英文名称: 5-amino-7-[2-(2',4',5'-tribromo)phenylethyl]-2-(2-furyl)-pyrazolo[4,3-e]-1,2,4-triazolo[1,5-c]pyrimidine
• 英文别名: 4-(Furan-2-yl)-10-[2-(2,4,5-tribromophenyl)ethyl]-3,5,6,8,10,11-hexazatricyclo[7.3.0.02,6]dodeca-1(9),2,4,7,11-pentaen-7-amine
• CAS: 181622-20-8
• 化学式: C₁₈H₁₂Br₃N₇O
• 分子量: 582.052
• InChiKey: KPTQFAWHBROXNC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  29
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  100
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  5-amino-7-[2-(2',4',5'-tribromo)phenylethyl]-2-(2-furyl)-pyrazolo[4,3-e]-1,2,4-triazolo[1,5-c]pyrimidine 在 超重氢 作用下， 生成 [3H]-Sch 58261
  参考文献：
  名称：

  Binding of the radioligand [3H]-SCH 58261, a new non-xanthine A2A adenosine receptor antagonist, to rat striatal membranes

  摘要：

  1 The present study describes the binding to rat striatal A(2A) adenosine receptors of the new potent and selective antagonist radioligand, [H-3]-5-amino-7-(2-phenylethyl)-2-(2-furyl)-pyrazolo[4,3-e]-1,2,4-triazolo [1,5-c] pyrimidine, [H-3]-SCH 58261.2 [H-3]-SCH 58261 specific binding to rat striatal membranes (>90%) was saturable, reversible and dependent upon protein concentration. Saturation experiments revealed that [H-3]-SCH 58261 labelled a single class of recognition sites with high affinity (K-d=0.70 nM) and limited capacity (apparent B-max=971 fmol mg(-1) of protein). The presence of 100 mu M GTP in the incubation mixture did not modify [H-3]-SCH 58261 binding parameters.3 Competition experiments showed that [H-3]-SCH 58261 binding is consistent with the labelling of A(2A) striatal receptors. Adenosine receptor agonists competed with the binding of 0.2 nM [H-3]-SCH 58261 with the following order of potency: 2-hexynyl-5'-N-ethyl carboxamidoadenosine (2HE-NECA)>5'-N-ethylcarboxamidoadenosine (NECA)>2-[4-(2-carboxyerhyl)-phenethylamino]-5'-N-ethylcarboxamidoadenosine (CGS 21680)>2-phenylaminoadenosine (CV 1808)>R-N-6-phenylisopropyiadenosine (R-PIA)>N-6-cyclohexyladenosine (CHA)=2-chloro-N-6-cyclopentyladenosine (CCPA)>S-N-6-phenylisopropyladenosine (S-PIA).4 Adenosine antagonists inhibited [H-3]-SCH 55261 binding with the following order: 5-amino-9-chloro-2-(2-furyl)-[1,2,4]-triazoio[1,5-c] quinazoline (CGS 15943)>5-amino-8-(4-fluorobenzyl)-2-(2-furyl)-pyrazolo [4,3-e]-1,2,4-triazolo [1,5-c] pyrimidine (8FB-PTP)=SCH 5826l>xanthine amine congener (XAC)=(E,18%-Z,82%)7-methyl-8-(3,4-dimethoxystyryl)-1,3-dipropylxanthine (KF 17837S)>8-cyclopentyl-1,3-dipropylxanthine (DPCPX)greater than or equal to 8-phenyltheophylline (8-PT).5 The K-i values for adenosine antagonists were similar to those labelled with the A(2A) agonist [H-3]-CGS 21680. Affinities of agonists were generally lower. The A(1)-selective agonist, R-PIA, was found to be about 9 fold more potent than its stereoisomer, S-PIA, thus showing the stereoselectivity of [K-3]-SCH 58261 binding. Except for 8-PT, the adenosine agonists and antagonists examined inhibited [H-3]-SCH 58261 binding with Hill coefficients not significantly different from unity.6 The present results indicate that [H-3]-SCH 58261 is the first non-xanthine adenosine antagonist radioligand which directly labels A(2A) Striatal receptors. High receptor affinity. good selectivity and very low non-specific binding make [H-3]-SCH 5826] an excellent probe for studying the A(2A) adenosine receptor subtype in mammalian brain.

  DOI：

  10.1111/j.1476-5381.1996.tb15296.x
• 作为产物：
  描述：

  2-呋喃甲酰肼 在 盐酸 、 对甲苯磺酸 作用下， 以 1,4-二氧六环 为溶剂， 反应 10.5h， 生成 5-amino-7-[2-(2',4',5'-tribromo)phenylethyl]-2-(2-furyl)-pyrazolo[4,3-e]-1,2,4-triazolo[1,5-c]pyrimidine
  参考文献：
  名称：

  Synthesis of the tritium labeled SCH 58261, a new non-xanthine A2A adenosine receptor antagonist

  摘要：

  The tritium labeled form of 5-amino-7-(2-phenylethyl)-2-(2-furyl)-pyrazolo[4,3-e] 1,2,4-triazolo[1,5-c]pyrimidine (H-3-SCH 58261) was obtained by reduction of 5-amino-7-[2-(2',4',5'-tribromo)-phenylethyl]-2-(2-furyl)-pyrazolo[4,3-e]1,2,4-triazolo[1,5-c]pyrimidine with tritium gas in the presence of 10% Pd-C. Final product was purified by HPLC to give the title H-3-SCH 58261 with radiochemical purity of 99% and specific activity of 68.6 Ci/mmol. H-3-SCH 58261 bound A(2A) receptors in rat striatal membranes (specific binding > 90%) with K-d acid B-max value of 0.70 nM and 971 fmol/mg of protein, respectively. H-3-SCH 58261 represents a useful tool for a further characterization of A(2A) adenosine receptor subtype.

  DOI：

  10.1002/(sici)1099-1344(199608)38:8<725::aid-jlcr885>3.0.co;2-g

文献信息

• Synthesis of the tritium labeled SCH 58261, a new non-xanthine A2A adenosine receptor antagonist
  作者：Pier Giovanni Baraldi、Barbara Cacciari、Silvio Dionisotti、Judith Egan、Giampiero Spalluto、Cristina Zocchi

  DOI：10.1002/(sici)1099-1344(199608)38:8<725::aid-jlcr885>3.0.co;2-g

  日期：1996.8

  The tritium labeled form of 5-amino-7-(2-phenylethyl)-2-(2-furyl)-pyrazolo[4,3-e] 1,2,4-triazolo[1,5-c]pyrimidine (H-3-SCH 58261) was obtained by reduction of 5-amino-7-[2-(2',4',5'-tribromo)-phenylethyl]-2-(2-furyl)-pyrazolo[4,3-e]1,2,4-triazolo[1,5-c]pyrimidine with tritium gas in the presence of 10% Pd-C. Final product was purified by HPLC to give the title H-3-SCH 58261 with radiochemical purity of 99% and specific activity of 68.6 Ci/mmol. H-3-SCH 58261 bound A(2A) receptors in rat striatal membranes (specific binding > 90%) with K-d acid B-max value of 0.70 nM and 971 fmol/mg of protein, respectively. H-3-SCH 58261 represents a useful tool for a further characterization of A(2A) adenosine receptor subtype.
• Binding of the radioligand [3H]-SCH 58261, a new non-xanthine A2A adenosine receptor antagonist, to rat striatal membranes
  作者：Cristina Zocchi、Ennio Ongini、Silvia Ferrara、Pier Giovanni Baraldi、Silvio Dionisotti

  DOI：10.1111/j.1476-5381.1996.tb15296.x

  日期：1996.4

  1 The present study describes the binding to rat striatal A(2A) adenosine receptors of the new potent and selective antagonist radioligand, [H-3]-5-amino-7-(2-phenylethyl)-2-(2-furyl)-pyrazolo[4,3-e]-1,2,4-triazolo [1,5-c] pyrimidine, [H-3]-SCH 58261.2 [H-3]-SCH 58261 specific binding to rat striatal membranes (>90%) was saturable, reversible and dependent upon protein concentration. Saturation experiments revealed that [H-3]-SCH 58261 labelled a single class of recognition sites with high affinity (K-d=0.70 nM) and limited capacity (apparent B-max=971 fmol mg(-1) of protein). The presence of 100 mu M GTP in the incubation mixture did not modify [H-3]-SCH 58261 binding parameters.3 Competition experiments showed that [H-3]-SCH 58261 binding is consistent with the labelling of A(2A) striatal receptors. Adenosine receptor agonists competed with the binding of 0.2 nM [H-3]-SCH 58261 with the following order of potency: 2-hexynyl-5'-N-ethyl carboxamidoadenosine (2HE-NECA)>5'-N-ethylcarboxamidoadenosine (NECA)>2-[4-(2-carboxyerhyl)-phenethylamino]-5'-N-ethylcarboxamidoadenosine (CGS 21680)>2-phenylaminoadenosine (CV 1808)>R-N-6-phenylisopropyiadenosine (R-PIA)>N-6-cyclohexyladenosine (CHA)=2-chloro-N-6-cyclopentyladenosine (CCPA)>S-N-6-phenylisopropyladenosine (S-PIA).4 Adenosine antagonists inhibited [H-3]-SCH 55261 binding with the following order: 5-amino-9-chloro-2-(2-furyl)-[1,2,4]-triazoio[1,5-c] quinazoline (CGS 15943)>5-amino-8-(4-fluorobenzyl)-2-(2-furyl)-pyrazolo [4,3-e]-1,2,4-triazolo [1,5-c] pyrimidine (8FB-PTP)=SCH 5826l>xanthine amine congener (XAC)=(E,18%-Z,82%)7-methyl-8-(3,4-dimethoxystyryl)-1,3-dipropylxanthine (KF 17837S)>8-cyclopentyl-1,3-dipropylxanthine (DPCPX)greater than or equal to 8-phenyltheophylline (8-PT).5 The K-i values for adenosine antagonists were similar to those labelled with the A(2A) agonist [H-3]-CGS 21680. Affinities of agonists were generally lower. The A(1)-selective agonist, R-PIA, was found to be about 9 fold more potent than its stereoisomer, S-PIA, thus showing the stereoselectivity of [K-3]-SCH 58261 binding. Except for 8-PT, the adenosine agonists and antagonists examined inhibited [H-3]-SCH 58261 binding with Hill coefficients not significantly different from unity.6 The present results indicate that [H-3]-SCH 58261 is the first non-xanthine adenosine antagonist radioligand which directly labels A(2A) Striatal receptors. High receptor affinity. good selectivity and very low non-specific binding make [H-3]-SCH 5826] an excellent probe for studying the A(2A) adenosine receptor subtype in mammalian brain.