S-1'-[18F]fluorocarazolol

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: S-1'-[18F]fluorocarazolol
• 英文别名: 2'-(R)-<18F>fluorocarazolol；(2S)-1-(9H-carbazol-4-yloxy)-3-(1-(18F)fluoranylpropan-2-ylamino)propan-2-ol
• 化学式: C₁₈H₂₁FN₂O₂
• 分子量: 315.377
• InChiKey: QHLGXPUIUKSADT-UIBZNNCISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  23
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  57.3
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  [18F]fluoroacetone 、 (2S)-3-(9H-carbazol-4-yloxy)-2-hydroxy-propylamine 在 sodium cyanoborohydride 、 溶剂黄146 作用下， 以 甲醇 为溶剂， 反应 0.25h， 生成 S-1'-[18F]fluorocarazolol
  参考文献：
  名称：

  Synthesis, Binding Properties, and 18F Labeling of Fluorocarazolol, a High-Affinity .beta.-Adrenergic Receptor Antagonist

  摘要：

  New beta-adrenergic receptor antagonists, 2-(R)-(+)- and 2-(S)-(-)-1-(9H-earbazol-4-yl-oxy)-3-[[1-(fluoromethyl)ethyl]amino]-2-propanol ((S)- and (R)-fluorocarazolols), were labeled with fluorine-18 at the no-carrier-added level by reductive alkylation of desisopropylcarazolol (4-(2-hydroxy-3-amino-1-propoxy)carbazole) with [F-18]fluoroacetone. The latter was prepared by nucleophilic substitution of fluoride on acetol tosylate and may serve as a useful synthetic precursor for other radiotracers. The radiochemical yield of [F-18]fluorocarazolol (500-1200 Ci/mmol) from [F-18]fluoride was 40 +/- 10% at the end of the 45 min synthesis. Chiral HPLC showed >99% enantiomeric purity of 2-(S)- and 2-(R)- [F-18] fluorocarazolols. The log P of fluorocarazolol was 2.2 at pH 7.4. The in vitro K-D values of(S)- and (R)-fluorocarazolol for the beta-adrenergic receptor were measured in a rat heart preparation to be K-D= 68 and 1128 pM, respectively. Biodistribution experiments in mice demonstrated specific beta-adrenergic receptor binding of (S)-[F-18]fluorocarazolol. (R)-[F-18]fluorocarazolol showed no observable specific binding to beta-receptors in vivo. The uptake of (R)-[F-18]fluorocarazolol may therefore be used as an estimation of nonspecific binding. Positron emission tomography images of pigs showed receptor-specific uptake of(S)-[F-18]fluorocarazolol in the heart and lung. Washout of dissociated ligand from the tissue was observed only after 70 min postinjection. The maximum ratio of specific to nonspecific uptake in pig heart and lung was ca. 10 at 150 min postinjection. Observed levels of fluorocarazolol metabolites in mouse and pig blood were relatively low and remained fairly constant during the period from 10 to 180 min postinjection. These results indicate that (S)-(-)-[F-18]fluorocarazolol is of interest for use as a radiopharmaceutical for estimation of beta-adrenergic receptors with positron tomography.

  DOI：

  10.1021/jm00046a005

文献信息

• Myocardial and pulmonary uptake of S-1′-[18F]fluorocarazolol in intact rats reflects radioligand binding to β-adrenoceptors
  作者：Aren Van Waarde、Philip H. Elsinga、Otto-Erich Brodde、Gerben M. Visser、Willem Vaalburg

  DOI：10.1016/0014-2999(94)00636-l

  日期：1995.1

  The biodistribution of S-(-)-4-(2-hydroxy-3-(1'-[18F]fluoroisopropyl)- aminopropoxy)carbazole ([18F]S-fluorocarazolol, a non-selective beta-adrenoceptor antagonist) was studied in rats (60 min after 18F injection when specific binding in peripheral organs was maximal). 18F uptake in brain, erythrocytes, heart and lung appeared to be linked to beta-adrenoceptors. CGP-20712A and ICI-89,406 inhibited 18F uptake in heart (predominantly beta 1-adrenoceptors) more potently than in lungs (predominantly beta 2-adrenoceptors). In contrast, ICI-118,551 and procaterol were more potent in the lungs than in the heart. ICI-118,551 inhibited 18F uptake in cerebellum (predominantly beta 2-adrenoceptors) more potently than in cerebral cortex (predominantly beta 1-adrenoceptors). Stereoselectivity of the in vivo binding was demonstrated since S-(-)-propranolol inhibited uptake in target tissues more effectively than R-(+)-propranolol. Myocardial and cerebral imaging may be hampered by poor heart-to-lung contrast and low signal-to-noise ratios, but [18F]S-fluorocarazolol seems suitable for positron emission tomography (PET) of pulmonary beta-adrenoceptors.
• Synthesis, Binding Properties, and 18F Labeling of Fluorocarazolol, a High-Affinity .beta.-Adrenergic Receptor Antagonist
  作者：Lei Zheng、Marc S. Berridge、Paul Ernsberger

  DOI：10.1021/jm00046a005

  日期：1994.9

  New beta-adrenergic receptor antagonists, 2-(R)-(+)- and 2-(S)-(-)-1-(9H-earbazol-4-yl-oxy)-3-[[1-(fluoromethyl)ethyl]amino]-2-propanol ((S)- and (R)-fluorocarazolols), were labeled with fluorine-18 at the no-carrier-added level by reductive alkylation of desisopropylcarazolol (4-(2-hydroxy-3-amino-1-propoxy)carbazole) with [F-18]fluoroacetone. The latter was prepared by nucleophilic substitution of fluoride on acetol tosylate and may serve as a useful synthetic precursor for other radiotracers. The radiochemical yield of [F-18]fluorocarazolol (500-1200 Ci/mmol) from [F-18]fluoride was 40 +/- 10% at the end of the 45 min synthesis. Chiral HPLC showed >99% enantiomeric purity of 2-(S)- and 2-(R)- [F-18] fluorocarazolols. The log P of fluorocarazolol was 2.2 at pH 7.4. The in vitro K-D values of(S)- and (R)-fluorocarazolol for the beta-adrenergic receptor were measured in a rat heart preparation to be K-D= 68 and 1128 pM, respectively. Biodistribution experiments in mice demonstrated specific beta-adrenergic receptor binding of (S)-[F-18]fluorocarazolol. (R)-[F-18]fluorocarazolol showed no observable specific binding to beta-receptors in vivo. The uptake of (R)-[F-18]fluorocarazolol may therefore be used as an estimation of nonspecific binding. Positron emission tomography images of pigs showed receptor-specific uptake of(S)-[F-18]fluorocarazolol in the heart and lung. Washout of dissociated ligand from the tissue was observed only after 70 min postinjection. The maximum ratio of specific to nonspecific uptake in pig heart and lung was ca. 10 at 150 min postinjection. Observed levels of fluorocarazolol metabolites in mouse and pig blood were relatively low and remained fairly constant during the period from 10 to 180 min postinjection. These results indicate that (S)-(-)-[F-18]fluorocarazolol is of interest for use as a radiopharmaceutical for estimation of beta-adrenergic receptors with positron tomography.