8-cyclopentyl-3-(3-hydroxypropyl)-7-pivaloyloxymethyl-1-propylxanthine | 200557-11-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 咪唑并嘧啶类
• 英文名称: 8-cyclopentyl-3-(3-hydroxypropyl)-7-pivaloyloxymethyl-1-propylxanthine
• 英文别名: [8-Cyclopentyl-3-(3-hydroxypropyl)-2,6-dioxo-1-propylpurin-7-yl]methyl 2,2-dimethylpropanoate
• CAS: 200557-11-5
• 化学式: C₂₂H₃₄N₄O₅
• 分子量: 434.536
• InChiKey: HKZYJZZSAWULLH-UHFFFAOYSA-N

物化性质

• 沸点：
  630.0±65.0 °C(Predicted)
• 密度：
  1.29±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  31
• 可旋转键数：
  10
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.73
• 拓扑面积：
  105
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  8-cyclopentyl-3-(3-hydroxypropyl)-7-pivaloyloxymethyl-1-propylxanthine 在 sodium hydroxide 作用下， 以 二甲基亚砜 为溶剂， 反应 0.5h， 以89%的产率得到PSB-16
  参考文献：
  名称：

  A₁ Adenosine Receptor Antagonists as Ligands for Positron Emission Tomography (PET) and Single-Photon Emission Tomography (SPET)

  摘要：

  The high affinity of 8-cyclopentyl-1,3-dipropylxanthine (CPX) for the A(1) adenosine receptor (A(1)AR) provides a good lead for developing radioligands suitable for positron emission tomography (PET) and single-photon emission tomography (SPET). This study tested the hypothesis that the kinds of chemical modifications made in the synthesis of CPX analogues containing carbon-ii, fluorine-18, or radioiodine will not alter affinity for the A(1)AR. This report describes the synthesis and radioligand binding assays of unlabeled CPX analogues having methyl, 2-methoxyethyl, 2-fluoropropyl, or 3-fluoropropyl substituents, respectively, at either N-1 (13a-d) or N-3 (8a-d) or an (E)-3-iodoprop-2-en-1-yl substituent at N-3 (8f). Compounds 8d,f and 13b,d antagonized the binding of [H-3]CPX to the A(1)AR of rat brain with affinities similar to those of CPX; compound 8c was twice as potent as CPX. Analogues 8a,b and 13a were less potent than CPX, but for each the K-i of antagonism was greater than or equal to 0.5 nM. Attempts to iodinate the 8-(4-hydroxyphenyl) analogue of CPX failed, probably because the xanthine substituent strongly deactivated the phenol toward electrophilic iodination. In summary, several of the modifications of the propyl groups of CPX needed to produce ligands for imaging by PET and SPET preserve or enhance affinity for the A(1)AR.

  DOI：

  10.1021/jm9705465
• 作为产物：
  描述：

  环戊基甲酰氯 在 palladium on activated charcoal sodium hydroxide 、 ammonium formate 、 sodium carbonate 作用下， 以 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 28.25h， 生成 8-cyclopentyl-3-(3-hydroxypropyl)-7-pivaloyloxymethyl-1-propylxanthine
  参考文献：
  名称：

  A₁ Adenosine Receptor Antagonists as Ligands for Positron Emission Tomography (PET) and Single-Photon Emission Tomography (SPET)

  摘要：

  The high affinity of 8-cyclopentyl-1,3-dipropylxanthine (CPX) for the A(1) adenosine receptor (A(1)AR) provides a good lead for developing radioligands suitable for positron emission tomography (PET) and single-photon emission tomography (SPET). This study tested the hypothesis that the kinds of chemical modifications made in the synthesis of CPX analogues containing carbon-ii, fluorine-18, or radioiodine will not alter affinity for the A(1)AR. This report describes the synthesis and radioligand binding assays of unlabeled CPX analogues having methyl, 2-methoxyethyl, 2-fluoropropyl, or 3-fluoropropyl substituents, respectively, at either N-1 (13a-d) or N-3 (8a-d) or an (E)-3-iodoprop-2-en-1-yl substituent at N-3 (8f). Compounds 8d,f and 13b,d antagonized the binding of [H-3]CPX to the A(1)AR of rat brain with affinities similar to those of CPX; compound 8c was twice as potent as CPX. Analogues 8a,b and 13a were less potent than CPX, but for each the K-i of antagonism was greater than or equal to 0.5 nM. Attempts to iodinate the 8-(4-hydroxyphenyl) analogue of CPX failed, probably because the xanthine substituent strongly deactivated the phenol toward electrophilic iodination. In summary, several of the modifications of the propyl groups of CPX needed to produce ligands for imaging by PET and SPET preserve or enhance affinity for the A(1)AR.

  DOI：

  10.1021/jm9705465

文献信息

• Synthesis and Evaluation of No-Carrier-Added 8-Cyclopentyl-3-(3-[¹⁸F]fluoropropyl)-1-propylxanthine ([¹⁸F]CPFPX):  A Potent and Selective A₁-Adenosine Receptor Antagonist for in Vivo Imaging
  作者：Marcus H. Holschbach、Ray A. Olsson、Dirk Bier、Walter Wutz、Wiebke Sihver、Manfred Schüller、Bettina Palm、Heinz H. Coenen

  DOI：10.1021/jm020905i

  日期：2002.11.1

  describes the precursor synthesis and the no-carrier-added (nca) radiosynthesis of the new A(1) adenosine receptor (A(1)AR) antagonist [(18)F]8-cyclopentyl-3-(3-fluoropropyl)-1-propylxanthine (CPFPX), 3, with fluorine-18 (half-life = 109.6 min). Nucleophilic radiofluorination of the precursor tosylate 8-cyclopentyl-3-(3-tosyloxypropyl)-7-pivaloyloxymethyl-1-propylxanthine, 2, with nca [(18)F]KF under aminopolyether-mediated

  这份报告描述了新的A（1）腺苷受体（A（1）AR）拮抗剂[（18）F] 8-环戊基-3-（3-氟丙基）的前体合成和无载体的（nca）放射合成）-1-丙基黄嘌呤（CPFPX），3，氟18（半衰期= 109.6分钟）。在氨基聚醚介导的条件下，用nca [（18）F] KF对前体甲苯磺酸酯化8-环戊基-3-（3-甲苯磺酰氧基丙基）-7-新戊酰氧基甲基-1-丙基黄嘌呤进行亲核放射性氟化（Kryptofix 2.2.2 / K（ 2）CO（3）），然后进行脱保护非常简单，在配制后，放射配体就可以注射了，放射化学产率为45 +/- 7％，放射化学纯度为> 98％，比放射性为> 270 GBq /微摩尔（> 7.2 Ci / micromol）。准备时间平均为55分钟。事实证明，该合成方法可实现高批量生产（约7个）。5 GBq）在常规生产中（n = 120次运行）。对放射性示踪剂进行了体外和体内药理学评
• A₁ Adenosine Receptor Antagonists as Ligands for Positron Emission Tomography (PET) and Single-Photon Emission Tomography (SPET)
  作者：Marcus H. Holschbach、Thomas Fein、Christof Krummeich、Robert G. Lewis、Walter Wutz、Ulrich Schwabe、Dieter Unterlugauer、Ray A. Olsson

  DOI：10.1021/jm9705465

  日期：1998.2.1

  The high affinity of 8-cyclopentyl-1,3-dipropylxanthine (CPX) for the A(1) adenosine receptor (A(1)AR) provides a good lead for developing radioligands suitable for positron emission tomography (PET) and single-photon emission tomography (SPET). This study tested the hypothesis that the kinds of chemical modifications made in the synthesis of CPX analogues containing carbon-ii, fluorine-18, or radioiodine will not alter affinity for the A(1)AR. This report describes the synthesis and radioligand binding assays of unlabeled CPX analogues having methyl, 2-methoxyethyl, 2-fluoropropyl, or 3-fluoropropyl substituents, respectively, at either N-1 (13a-d) or N-3 (8a-d) or an (E)-3-iodoprop-2-en-1-yl substituent at N-3 (8f). Compounds 8d,f and 13b,d antagonized the binding of [H-3]CPX to the A(1)AR of rat brain with affinities similar to those of CPX; compound 8c was twice as potent as CPX. Analogues 8a,b and 13a were less potent than CPX, but for each the K-i of antagonism was greater than or equal to 0.5 nM. Attempts to iodinate the 8-(4-hydroxyphenyl) analogue of CPX failed, probably because the xanthine substituent strongly deactivated the phenol toward electrophilic iodination. In summary, several of the modifications of the propyl groups of CPX needed to produce ligands for imaging by PET and SPET preserve or enhance affinity for the A(1)AR.