Synthesis of 1-(2,4-dichlorophenyl)-4-cyano-5-(4-[11C] methoxyphenyl)-N-(piperidin-1-yl)-1H-pyrazole-3-carboxamide ([ 11C]JHU75528) and 1-(2-bromophenyl)-4-cyano-5-(4-[ 11C]methoxyphenyl)-N-(piperidin-1-yl)-1H-pyrazole-3-carboxamide ([11C]JHU75575) as potential radioligands for PET imaging of cerebral cannabinoid receptor

Hong Fan; Hayden T. Ravert; Daniel P. Holt; Robert F. Dannals; Andrew G. Horti

doi:10.1002/jlcr.1125

Synthesis of 1-(2,4-dichlorophenyl)-4-cyano-5-(4-[¹¹C] methoxyphenyl)-N-(piperidin-1-yl)-1H-pyrazole-3-carboxamide ([ ¹¹C]JHU75528) and 1-(2-bromophenyl)-4-cyano-5-(4-[ ¹¹C]methoxyphenyl)-N-(piperidin-1-yl)-1H-pyrazole-3-carboxamide ([¹¹C]JHU75575) as potential radioligands for PET imaging of cerebral cannabinoid receptor

Hong Fan, Hayden T. Ravert, Daniel P. Holt, Robert F. Dannals, Andrew G. Horti

School of Medicine

Research output: Contribution to journal › Article › peer-review

30 Scopus citations

Abstract

Two novel ligands for cerebral cannabinoid receptor (CB1), 1-(2,4-dichlorophenyl)-4-cyano-5-(4-methoxyphenyl)-N-(piperidin-1-yl) -1H-pyrazole-3-carboxamide (JHU75528) and 1-(2-bromophenyl)-4-cyano-5-(4- methoxyphenyl)-N-(piperidin-1-yl)-1H-pyrazole-3-carboxamide (JHU75575) have been synthesized. Both JHU75528 and JHU75575 display a combination of higher binding affinity and lower lipophilicity than those of Rimonabant (SR141716), a high affinity CB1 selective antagonist, and AM281, the only available ligand for emission tomography imaging of CB1 in human subjects. Radiolabeled [ ¹¹C]JHU75528 and [¹¹C]JHU75575 were prepared by reaction of [¹¹C]methyl iodide with nor-methyl precursors. The average radiochemical yield, specific radioactivity, and radiochemical purity of [ ¹¹C]JHU75528 were 16%, 235 GBq/μmol (6360 mCi/μmol), and 99%, respectively; those of [¹¹C]JHU75575 were 8%, 196 GBq/μmol (5308 mCi/μmol), and 99%, respectively. Both ligands hold promise as PET radioligands for imaging CB1 receptor.

Original language	English (US)
Pages (from-to)	1021-1036
Number of pages	16
Journal	Journal of Labelled Compounds and Radiopharmaceuticals
Volume	49
Issue number	12
DOIs	https://doi.org/10.1002/jlcr.1125
State	Published - Oct 30 2006

Keywords

Cannabinoid receptor
Carbon-11
Positron emission tomography
Rimonabant
SR141716

ASJC Scopus subject areas

Analytical Chemistry
Biochemistry
Radiology Nuclear Medicine and imaging
Drug Discovery
Spectroscopy
Organic Chemistry

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Fan, H., Ravert, H. T., Holt, D. P., Dannals, R. F., & Horti, A. G. (2006). Synthesis of 1-(2,4-dichlorophenyl)-4-cyano-5-(4-[¹¹C] methoxyphenyl)-N-(piperidin-1-yl)-1H-pyrazole-3-carboxamide ([ ¹¹C]JHU75528) and 1-(2-bromophenyl)-4-cyano-5-(4-[ ¹¹C]methoxyphenyl)-N-(piperidin-1-yl)-1H-pyrazole-3-carboxamide ([¹¹C]JHU75575) as potential radioligands for PET imaging of cerebral cannabinoid receptor. Journal of Labelled Compounds and Radiopharmaceuticals, 49(12), 1021-1036. https://doi.org/10.1002/jlcr.1125

Synthesis of 1-(2,4-dichlorophenyl)-4-cyano-5-(4-[¹¹C] methoxyphenyl)-N-(piperidin-1-yl)-1H-pyrazole-3-carboxamide ([ ¹¹C]JHU75528) and 1-(2-bromophenyl)-4-cyano-5-(4-[ ¹¹C]methoxyphenyl)-N-(piperidin-1-yl)-1H-pyrazole-3-carboxamide ([¹¹C]JHU75575) as potential radioligands for PET imaging of cerebral cannabinoid receptor. / Fan, Hong; Ravert, Hayden T.; Holt, Daniel P. et al.
In: Journal of Labelled Compounds and Radiopharmaceuticals, Vol. 49, No. 12, 30.10.2006, p. 1021-1036.

Research output: Contribution to journal › Article › peer-review

Fan, H, Ravert, HT, Holt, DP , Dannals, RF & Horti, AG 2006, 'Synthesis of 1-(2,4-dichlorophenyl)-4-cyano-5-(4-[¹¹C] methoxyphenyl)-N-(piperidin-1-yl)-1H-pyrazole-3-carboxamide ([ ¹¹C]JHU75528) and 1-(2-bromophenyl)-4-cyano-5-(4-[ ¹¹C]methoxyphenyl)-N-(piperidin-1-yl)-1H-pyrazole-3-carboxamide ([¹¹C]JHU75575) as potential radioligands for PET imaging of cerebral cannabinoid receptor', Journal of Labelled Compounds and Radiopharmaceuticals, vol. 49, no. 12, pp. 1021-1036. https://doi.org/10.1002/jlcr.1125

Fan H, Ravert HT, Holt DP , Dannals RF , Horti AG. Synthesis of 1-(2,4-dichlorophenyl)-4-cyano-5-(4-[¹¹C] methoxyphenyl)-N-(piperidin-1-yl)-1H-pyrazole-3-carboxamide ([ ¹¹C]JHU75528) and 1-(2-bromophenyl)-4-cyano-5-(4-[ ¹¹C]methoxyphenyl)-N-(piperidin-1-yl)-1H-pyrazole-3-carboxamide ([¹¹C]JHU75575) as potential radioligands for PET imaging of cerebral cannabinoid receptor. Journal of Labelled Compounds and Radiopharmaceuticals. 2006 Oct 30;49(12):1021-1036. doi: 10.1002/jlcr.1125

Fan, Hong ; Ravert, Hayden T. ; Holt, Daniel P. et al. / Synthesis of 1-(2,4-dichlorophenyl)-4-cyano-5-(4-[¹¹C] methoxyphenyl)-N-(piperidin-1-yl)-1H-pyrazole-3-carboxamide ([ ¹¹C]JHU75528) and 1-(2-bromophenyl)-4-cyano-5-(4-[ ¹¹C]methoxyphenyl)-N-(piperidin-1-yl)-1H-pyrazole-3-carboxamide ([¹¹C]JHU75575) as potential radioligands for PET imaging of cerebral cannabinoid receptor. In: Journal of Labelled Compounds and Radiopharmaceuticals. 2006 ; Vol. 49, No. 12. pp. 1021-1036.

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title = "Synthesis of 1-(2,4-dichlorophenyl)-4-cyano-5-(4-[11C] methoxyphenyl)-N-(piperidin-1-yl)-1H-pyrazole-3-carboxamide ([ 11C]JHU75528) and 1-(2-bromophenyl)-4-cyano-5-(4-[ 11C]methoxyphenyl)-N-(piperidin-1-yl)-1H-pyrazole-3-carboxamide ([11C]JHU75575) as potential radioligands for PET imaging of cerebral cannabinoid receptor",

abstract = "Two novel ligands for cerebral cannabinoid receptor (CB1), 1-(2,4-dichlorophenyl)-4-cyano-5-(4-methoxyphenyl)-N-(piperidin-1-yl) -1H-pyrazole-3-carboxamide (JHU75528) and 1-(2-bromophenyl)-4-cyano-5-(4- methoxyphenyl)-N-(piperidin-1-yl)-1H-pyrazole-3-carboxamide (JHU75575) have been synthesized. Both JHU75528 and JHU75575 display a combination of higher binding affinity and lower lipophilicity than those of Rimonabant (SR141716), a high affinity CB1 selective antagonist, and AM281, the only available ligand for emission tomography imaging of CB1 in human subjects. Radiolabeled [ 11C]JHU75528 and [11C]JHU75575 were prepared by reaction of [11C]methyl iodide with nor-methyl precursors. The average radiochemical yield, specific radioactivity, and radiochemical purity of [ 11C]JHU75528 were 16%, 235 GBq/μmol (6360 mCi/μmol), and 99%, respectively; those of [11C]JHU75575 were 8%, 196 GBq/μmol (5308 mCi/μmol), and 99%, respectively. Both ligands hold promise as PET radioligands for imaging CB1 receptor.",

keywords = "Cannabinoid receptor, Carbon-11, Positron emission tomography, Rimonabant, SR141716",

author = "Hong Fan and Ravert, {Hayden T.} and Holt, {Daniel P.} and Dannals, {Robert F.} and Horti, {Andrew G.}",

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