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.
Journal Article (Journal Article)
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.
Full Text
Duke Authors
Cited Authors
- Yu, W; Wang, E; Voll, RJ; Miller, AH; Goodman, MM
Published Date
- June 1, 2008
Published In
Volume / Issue
- 16 / 11
Start / End Page
- 6145 - 6155
PubMed ID
- 18472268
Electronic International Standard Serial Number (EISSN)
- 1464-3391
Digital Object Identifier (DOI)
- 10.1016/j.bmc.2008.04.046
Language
- eng
Conference Location
- England