Synthesis and initial PET imaging of new potential dopamine D3 receptor radioligands (E)-4,3,2-[11C]methoxy-N-4-(4-(2-methoxyphenyl) piperazin-1-yl)butyl-cinnamoylamides

Mingzhang Gao, Bruce H. Mock, Gary D. Hutchins, Qi Huang Zheng

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

D3 receptor radioligands (E)-4,3,2-[11C]methoxy-N-4- (4-(2-methoxyphenyl)piperazin-1-yl)butyl-cinnamoylamides (4-[11C]MMC, [11C]1a; 3-[11C]MMC, [11C]1b; and 2-[ 11C]MMC, [11C]1c) were synthesized for evaluation as novel potential positron emission tomography (PET) imaging agents for brain D 3 receptors. The new tracers 4,3,2-[11C]MMCs were prepared by O-[11C]methylation of corresponding precursors (E)-4,3,2-hydroxy-N-4-(4-(2-methoxyphenyl)piperazin-1-yl)butyl-cinnamoylamides (4,3,2-HMCs) using [11C]methyl triflate and isolated by the solid-phase extraction (SPE) purification procedure with 40-65% radiochemical yields, decay corrected to end of bombardment (EOB), and a synthesis time of 15-20 min. The PET dynamic studies of the tracers [11C]1a-c in rats were performed using an animal PET scanner, IndyPET-II, developed in our laboratory. The results show that the brain uptake sequence was 4-[ 11C]MMC > 3-[11C]MMC > 2-[11C]MMC, which is consistent with their in vitro biological properties. The initial PET blocking studies of the tracers 4,3,2-[11C]MMCs with corresponding pretreatment drugs (E)-4,3,2-methoxy-N-4-(4-(2-methoxyphenyl)piperazin-1-yl) butyl-cinnamoylamides (4,3,2-MMCs, 1a-c) had no effect on 4,3,2-[ 11C]MMCs-PET rat brain imaging. These results suggest that the localization of 4,3,2-[11C]MMCs in rat brain is mediated by nonspecific processes, and the visualization of 4,3,2-[11C]MMCs-PET in rat brain is related to nonspecific binding.

Original languageEnglish (US)
Pages (from-to)6233-6243
Number of pages11
JournalBioorganic and Medicinal Chemistry
Volume13
Issue number22
DOIs
StatePublished - Nov 15 2005

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Dopamine D3 Receptors
Positron emission tomography
Positron-Emission Tomography
Brain
Imaging techniques
Rats
Neuroimaging
Methylation
Solid Phase Extraction
Purification
Animals
Visualization
Pharmaceutical Preparations

Keywords

  • (E)-4,3,2-[C]Methoxy-N-(4-4-(2-methoxyphenyl)butyl- cinnamoylamides
  • Brain
  • D receptors
  • Positron emission tomography
  • Radioligands

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Organic Chemistry
  • Drug Discovery
  • Pharmaceutical Science

Cite this

@article{d1249a887e2f49ab99adb5bc37b8cc2a,
title = "Synthesis and initial PET imaging of new potential dopamine D3 receptor radioligands (E)-4,3,2-[11C]methoxy-N-4-(4-(2-methoxyphenyl) piperazin-1-yl)butyl-cinnamoylamides",
abstract = "D3 receptor radioligands (E)-4,3,2-[11C]methoxy-N-4- (4-(2-methoxyphenyl)piperazin-1-yl)butyl-cinnamoylamides (4-[11C]MMC, [11C]1a; 3-[11C]MMC, [11C]1b; and 2-[ 11C]MMC, [11C]1c) were synthesized for evaluation as novel potential positron emission tomography (PET) imaging agents for brain D 3 receptors. The new tracers 4,3,2-[11C]MMCs were prepared by O-[11C]methylation of corresponding precursors (E)-4,3,2-hydroxy-N-4-(4-(2-methoxyphenyl)piperazin-1-yl)butyl-cinnamoylamides (4,3,2-HMCs) using [11C]methyl triflate and isolated by the solid-phase extraction (SPE) purification procedure with 40-65{\%} radiochemical yields, decay corrected to end of bombardment (EOB), and a synthesis time of 15-20 min. The PET dynamic studies of the tracers [11C]1a-c in rats were performed using an animal PET scanner, IndyPET-II, developed in our laboratory. The results show that the brain uptake sequence was 4-[ 11C]MMC > 3-[11C]MMC > 2-[11C]MMC, which is consistent with their in vitro biological properties. The initial PET blocking studies of the tracers 4,3,2-[11C]MMCs with corresponding pretreatment drugs (E)-4,3,2-methoxy-N-4-(4-(2-methoxyphenyl)piperazin-1-yl) butyl-cinnamoylamides (4,3,2-MMCs, 1a-c) had no effect on 4,3,2-[ 11C]MMCs-PET rat brain imaging. These results suggest that the localization of 4,3,2-[11C]MMCs in rat brain is mediated by nonspecific processes, and the visualization of 4,3,2-[11C]MMCs-PET in rat brain is related to nonspecific binding.",
keywords = "(E)-4,3,2-[C]Methoxy-N-(4-4-(2-methoxyphenyl)butyl- cinnamoylamides, Brain, D receptors, Positron emission tomography, Radioligands",
author = "Mingzhang Gao and Mock, {Bruce H.} and Hutchins, {Gary D.} and Zheng, {Qi Huang}",
year = "2005",
month = "11",
day = "15",
doi = "10.1016/j.bmc.2005.06.055",
language = "English (US)",
volume = "13",
pages = "6233--6243",
journal = "Bioorganic and Medicinal Chemistry",
issn = "0968-0896",
publisher = "Elsevier Limited",
number = "22",

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TY - JOUR

T1 - Synthesis and initial PET imaging of new potential dopamine D3 receptor radioligands (E)-4,3,2-[11C]methoxy-N-4-(4-(2-methoxyphenyl) piperazin-1-yl)butyl-cinnamoylamides

AU - Gao, Mingzhang

AU - Mock, Bruce H.

AU - Hutchins, Gary D.

AU - Zheng, Qi Huang

PY - 2005/11/15

Y1 - 2005/11/15

N2 - D3 receptor radioligands (E)-4,3,2-[11C]methoxy-N-4- (4-(2-methoxyphenyl)piperazin-1-yl)butyl-cinnamoylamides (4-[11C]MMC, [11C]1a; 3-[11C]MMC, [11C]1b; and 2-[ 11C]MMC, [11C]1c) were synthesized for evaluation as novel potential positron emission tomography (PET) imaging agents for brain D 3 receptors. The new tracers 4,3,2-[11C]MMCs were prepared by O-[11C]methylation of corresponding precursors (E)-4,3,2-hydroxy-N-4-(4-(2-methoxyphenyl)piperazin-1-yl)butyl-cinnamoylamides (4,3,2-HMCs) using [11C]methyl triflate and isolated by the solid-phase extraction (SPE) purification procedure with 40-65% radiochemical yields, decay corrected to end of bombardment (EOB), and a synthesis time of 15-20 min. The PET dynamic studies of the tracers [11C]1a-c in rats were performed using an animal PET scanner, IndyPET-II, developed in our laboratory. The results show that the brain uptake sequence was 4-[ 11C]MMC > 3-[11C]MMC > 2-[11C]MMC, which is consistent with their in vitro biological properties. The initial PET blocking studies of the tracers 4,3,2-[11C]MMCs with corresponding pretreatment drugs (E)-4,3,2-methoxy-N-4-(4-(2-methoxyphenyl)piperazin-1-yl) butyl-cinnamoylamides (4,3,2-MMCs, 1a-c) had no effect on 4,3,2-[ 11C]MMCs-PET rat brain imaging. These results suggest that the localization of 4,3,2-[11C]MMCs in rat brain is mediated by nonspecific processes, and the visualization of 4,3,2-[11C]MMCs-PET in rat brain is related to nonspecific binding.

AB - D3 receptor radioligands (E)-4,3,2-[11C]methoxy-N-4- (4-(2-methoxyphenyl)piperazin-1-yl)butyl-cinnamoylamides (4-[11C]MMC, [11C]1a; 3-[11C]MMC, [11C]1b; and 2-[ 11C]MMC, [11C]1c) were synthesized for evaluation as novel potential positron emission tomography (PET) imaging agents for brain D 3 receptors. The new tracers 4,3,2-[11C]MMCs were prepared by O-[11C]methylation of corresponding precursors (E)-4,3,2-hydroxy-N-4-(4-(2-methoxyphenyl)piperazin-1-yl)butyl-cinnamoylamides (4,3,2-HMCs) using [11C]methyl triflate and isolated by the solid-phase extraction (SPE) purification procedure with 40-65% radiochemical yields, decay corrected to end of bombardment (EOB), and a synthesis time of 15-20 min. The PET dynamic studies of the tracers [11C]1a-c in rats were performed using an animal PET scanner, IndyPET-II, developed in our laboratory. The results show that the brain uptake sequence was 4-[ 11C]MMC > 3-[11C]MMC > 2-[11C]MMC, which is consistent with their in vitro biological properties. The initial PET blocking studies of the tracers 4,3,2-[11C]MMCs with corresponding pretreatment drugs (E)-4,3,2-methoxy-N-4-(4-(2-methoxyphenyl)piperazin-1-yl) butyl-cinnamoylamides (4,3,2-MMCs, 1a-c) had no effect on 4,3,2-[ 11C]MMCs-PET rat brain imaging. These results suggest that the localization of 4,3,2-[11C]MMCs in rat brain is mediated by nonspecific processes, and the visualization of 4,3,2-[11C]MMCs-PET in rat brain is related to nonspecific binding.

KW - (E)-4,3,2-[C]Methoxy-N-(4-4-(2-methoxyphenyl)butyl- cinnamoylamides

KW - Brain

KW - D receptors

KW - Positron emission tomography

KW - Radioligands

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U2 - 10.1016/j.bmc.2005.06.055

DO - 10.1016/j.bmc.2005.06.055

M3 - Article

C2 - 16087340

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VL - 13

SP - 6233

EP - 6243

JO - Bioorganic and Medicinal Chemistry

JF - Bioorganic and Medicinal Chemistry

SN - 0968-0896

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