5-amino-1-(2,6-dichloro-4-trifluoromethyl-phenyl)-3-[3H3]-methylsulfanyl-1H-pyrazole-4-carbonitrile (CTOM): synthesis and characterization of a novel and selective insect GABA receptor radioligand.
Pyrazole 2a is a novel, potent ligand for insect GABA receptors obtained from housefly head membrane preparations (K(i)=8 nM). It is 500-fold selective against the mammalian receptor (mouse brain preparations). Its specifically tritiated version (2b) was synthesized by reduction of disulfide 10 with NaBH(4) followed by alkylation with [3H(3)]-CH(3)I.
Meegalla
Sanath K
SK
3-Dimensional Pharmaceuticals, Inc., 665 Stockton Drive, Suite 104, Exton, PA 19341, USA. meegalla@3dp.com
Doller
Dario
D
Silver
Gary M
GM
Wisnewski
Nancy
N
Soll
Richard M
RM
Dhanoa
Dale
D
D000818:Animals; D007313:Insecta; D015394:Molecular Structure; D009570:Nitriles / Q000138:chemical synthesis* / Q000493:pharmacokinetics*; D011720:Pyrazoles / Q000138:chemical synthesis* / Q000493:pharmacokinetics*; D011869:Radioligand Assay; D018079:Receptors, GABA / Q000737:chemistry* / Q000378:metabolism*; D013329:Structure-Activity Relationship; D014316:Tritium
C487478:5-amino-1-(2,6-dichloro-4-trifluoromethyl-phenyl)-3-(3H3)-methylsulfanyl-1H-pyrazole-4-carbonitrile; D009570:Nitriles; D011720:Pyrazoles; D018079:Receptors, GABA; D014316:Tritium