6-Chloro-3-(((1-[11C]methyl)-2-(S)-pyrrolidinyl)methoxy)-5-(2-fluoropyridin-4-yl)pyridine ([11C]JHU85270), a potent ligand for nicotinic acetylcholine receptor imaging by positron emission tomography.
6-Chloro-3-((1-methyl)-2-(S)-pyrrolidinyl)methoxy)-5-(2-fluoropyridin-4-yl)pyridine (JHU85270), a novel high-affinity ligand for the alpha4beta2 nicotine acetylcholine receptor (nAChR) (K(i)=86, 115 pM; K(i)(JHU85270)/K(i)(epibatidine)=1.7) with a log D(7.4)=1.6 was synthesized in 56% overall yield. [(11)C]JHU85270 was synthesized from [(11)C]-methyl iodide and the corresponding normethyl precursor. The average time of radiosynthesis, purification, and formulation was 37 min from the end of bombardment. The average radiochemical yield of [(11)C]JHU85270 was 37%+/-3% (non-decay corrected). The average specific radioactivity was 398+/-165 GBq/micromol (10750+/-4468 mCi/micromol) and the radiochemical purity was greater than 99%.
Gao
Yongjun
Y
Division of Nuclear Medicine, Department of Radiology, The Johns Hopkins University, School of Medicine, 600 North Wolfe Street, Baltimore, MD 21287-0816, USA.
Ravert
Hayden T
HT
Holt
Daniel
D
Dannals
Robert F
RF
Horti
Andrew G
AG
D000818:Animals; D001086:Arabinofuranosyluracil / Q000031:analogs & derivatives* / Q000737:chemistry / Q000302:isolation & purification; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism; D005462:Fluorine Radioisotopes / Q000737:chemistry* / Q000302:isolation & purification / Q000493:pharmacokinetics; D006801:Humans; D007553:Isotope Labeling / Q000379:methods; D049268:Positron-Emission Tomography / Q000379:methods*; D011725:Pyridines / Q000737:chemistry* / Q000493:pharmacokinetics*; D011759:Pyrrolidines / Q000737:chemistry* / Q000493:pharmacokinetics*; D019275:Radiopharmaceuticals / Q000138:chemical synthesis / Q000302:isolation & purification; D011978:Receptors, Nicotinic / Q000378:metabolism
C523702:6-chloro-3-(((1-methyl)-2-pyrrolidinyl)methoxy)-5-(2-fluoropyridin-4-yl)pyridine; D005462:Fluorine Radioisotopes; D011725:Pyridines; D011759:Pyrrolidines; D019275:Radiopharmaceuticals; D011978:Receptors, Nicotinic; D001086:Arabinofuranosyluracil; C034935:clevudine