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Bioorg Med Chem. 2008 Jun 1;16(11):6145-55. doi: 10.1016/j.bmc.2008.04.046. Epub 2008 Apr 25.

Synthesis, fluorine-18 radiolabeling, and in vitro characterization of 1-iodophenyl-N-methyl-N-fluoroalkyl-3-isoquinoline carboxamide derivatives as potential PET radioligands for imaging peripheral benzodiazepine receptor.

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1
Department of Radiology, School of Medicine, Emory University, Atlanta, GA 30322, USA.

Abstract

The isoquinoline carboxamide derivative 1-(2-chlorophenyl)-N-methyl-N-(1-methylpropyl)-3-isoquinoline carboxamide (PK11195) has been shown to bind strongly and selectively to the peripheral benzodiazepine receptor (PBR) binding sites. A series of PK11195 analogues have been synthesized and biologically characterized. The affinities of the analogues for the PBR were determined using in vitro competitive binding assays with [(3)H]PK11195 in rat kidney mitochondrial membranes. The results showed that the 1-(2-iodophenyl)-N-methyl-N-(3-fluoropropyl)-3-isoquinoline carboxamide (9a) was the most potent compound (K(i)=0.26nM) of this series and is an excellent lead ligand for additional studies for labeling with fluorine-18 to determine whether it possesses the desired in vivo performance in non-human primates by PET imaging. Thus, radiolabeling of 9a with fluorine-18 was developed.

PMID:
18472268
DOI:
10.1016/j.bmc.2008.04.046
[Indexed for MEDLINE]

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