Synthesis and receptor binding studies of halogenated N,N-dialkylel-(2-phenyl-1H-indol-3-yl)glyoxylamides to visualize peripheral benzodiazepine receptors with SPECT or PET.
A library of halogenated 2-arylindolyl-3-oxocarboxamides was prepared to develop radioligands to visualize cerebral PBR by SPECT and PET imaging. In vitro evaluation showed that most of the synthesized compounds were selective,high-affinity PBR ligands with adequate lipophilicity (log D7.4 in the range of 1.6-2.4). The iodinated derivative 11 (Ki = 2.6 nM) and the fluorinated analog 26 (Ki = 6.2 nM) displayed higher affinity than reference compounds.
Bennacef
Idriss
I
Yale School of Medicine, VA Connecticut HCS (116A2), West Haven, CT 06516, USA.
Haile
Colin N
CN
Schmidt
Anne
A
Koren
Andrei O
AO
Seibyl
John P
JP
Staley
Julie K
JK
Bois
Frederic
F
Baldwin
Ronald M
RM
Tamagnan
Gilles
G
D000478:Alkylation; D000577:Amides / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism*; D000818:Animals; D002540:Cerebral Cortex / Q000378:metabolism; D006168:Guinea Pigs; D006219:Halogens / Q000737:chemistry*; D007211:Indoles / Q000737:chemistry*; D007668:Kidney / Q000378:metabolism; D015394:Molecular Structure; D049268:Positron-Emission Tomography; D051381:Rats; D011963:Receptors, GABA-A / Q000378:metabolism*; D013329:Structure-Activity Relationship; D015899:Tomography, Emission-Computed, Single-Photon
D000577:Amides; D006219:Halogens; D007211:Indoles; D011963:Receptors, GABA-A; C030374:indole