The synthesis, evaluation, and molecular modeling of a series of 18F-labeled 4-anilidopiperidines with high affinities for the mu-opioid receptor (mu-OR) are reported. On the basis of the high brain uptake and selective retention in brain regions that contain a high concentration of the mu-OR, combined with a good metabolic stability, [18F]fluoro-pentyl carfentanil ([18F]4) and 2-(+/-)[18F]fluoropropyl-sufentanil ([18F]6) were selected as the lead compounds for further evaluation. The binding affinity to the human mu-OR was 0.74 and 0.13 nM for [18F]4 and [18F]6, respectively. In vitro autoradiography of [18F]4 and [18F]6 on rat brain sections produced patterns in accordance with the known distribution of mu-OR expression. Structure-activity relationships of the fluorinated compounds are discussed with respect to the interaction with an activated-state model of the mu-OR. Taken together, the in vivo and in vitro data indicate that [18F]4 and [18F]6 hold promise for studying the mu-opioid receptor in humans by means of positron emission tomography.

Syntheses, Biological Evaluation and Molecular Modeling of 18F-labeled 4-Anilidopiperidines as μ-Opioid Receptor Imaging Agents / G., Henriksen; S., Platzer; J., Marton; A., Hauser; A., Berthele; M., Schwaiger; Marinelli, Luciana; Lavecchia, Antonio; Novellino, Ettore; H. J., Wester. - In: JOURNAL OF MEDICINAL CHEMISTRY. - ISSN 0022-2623. - ELETTRONICO. - 48:(2005), pp. 7720-7732. [10.1021/jm0507274]

Syntheses, Biological Evaluation and Molecular Modeling of 18F-labeled 4-Anilidopiperidines as μ-Opioid Receptor Imaging Agents

MARINELLI, LUCIANA;LAVECCHIA, ANTONIO;NOVELLINO, ETTORE;
2005

Abstract

The synthesis, evaluation, and molecular modeling of a series of 18F-labeled 4-anilidopiperidines with high affinities for the mu-opioid receptor (mu-OR) are reported. On the basis of the high brain uptake and selective retention in brain regions that contain a high concentration of the mu-OR, combined with a good metabolic stability, [18F]fluoro-pentyl carfentanil ([18F]4) and 2-(+/-)[18F]fluoropropyl-sufentanil ([18F]6) were selected as the lead compounds for further evaluation. The binding affinity to the human mu-OR was 0.74 and 0.13 nM for [18F]4 and [18F]6, respectively. In vitro autoradiography of [18F]4 and [18F]6 on rat brain sections produced patterns in accordance with the known distribution of mu-OR expression. Structure-activity relationships of the fluorinated compounds are discussed with respect to the interaction with an activated-state model of the mu-OR. Taken together, the in vivo and in vitro data indicate that [18F]4 and [18F]6 hold promise for studying the mu-opioid receptor in humans by means of positron emission tomography.
2005
Syntheses, Biological Evaluation and Molecular Modeling of 18F-labeled 4-Anilidopiperidines as μ-Opioid Receptor Imaging Agents / G., Henriksen; S., Platzer; J., Marton; A., Hauser; A., Berthele; M., Schwaiger; Marinelli, Luciana; Lavecchia, Antonio; Novellino, Ettore; H. J., Wester. - In: JOURNAL OF MEDICINAL CHEMISTRY. - ISSN 0022-2623. - ELETTRONICO. - 48:(2005), pp. 7720-7732. [10.1021/jm0507274]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11588/201585
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