Development of [11C]L-159,884: a radiolabelled, nonpeptide angiotensin II antagonist that is useful for angiotensin II, AT1 receptor imaging.
[11C]L-159,884 ([11C] N-[[4'[(2-ethyl-5,7-dimethyl-3H- imidazo[4,5-b]pyridin-3-yl) methyl] [1,1'-biphenyl]-2-yl] sulfonyl]-4-methoxybenzamide) and [11C]L-162,574 ([11C] N-[[4'[2-ethyl-5,7- dimethyl-3H-imidazo[4,5-b] pyridin-3-yl)methyl] [1,1'-biphenyl]-2-yl]sulfonyl]-3- methoxybenzamide), both potent and selective ligands for the AT1 receptor, were prepared by C-11 methylation of the corresponding desmethyl phenolic precursors. The radiotracers were purified by semi-preparative reverse-phase HPLC. Non-decay corrected radiochemical yields were 5 and 3% for L-159,884 and L-162,574 respectively, and the average specific activity was 2979 mCi/mumol at end-of-synthesis (EOS). The average time of synthesis was 18 min.
Hamill
T G
TG
Department of Pharmacology, Merck Research Laboratories, West Point, PA 19486, USA.
Burns
H D
HD
Dannals
R F
RF
Mathews
W B
WB
Musachio
J L
JL
Ravert
H T
HT
Naylor
E M
EM
D000803:Angiotensin I / Q000378:metabolism*; D000804:Angiotensin II / Q000037:antagonists & inhibitors*; D057911:Angiotensin Receptor Antagonists; D002250:Carbon Radioisotopes / Q000737:chemistry*; D002851:Chromatography, High Pressure Liquid; D006847:Hydrocarbons, Iodinated / Q000737:chemistry; D007091:Image Processing, Computer-Assisted; D007093:Imidazoles / Q000138:chemical synthesis / Q000378:metabolism*; D007553:Isotope Labeling / Q000379:methods; D011725:Pyridines / Q000138:chemical synthesis / Q000378:metabolism*; D011945:Receptors, Angiotensin / Q000378:metabolism*; D014055:Tomography, Emission-Computed
D057911:Angiotensin Receptor Antagonists; D002250:Carbon Radioisotopes; D006847:Hydrocarbons, Iodinated; D007093:Imidazoles; C099072:L 162574; D011725:Pyridines; D011945:Receptors, Angiotensin; D000804:Angiotensin II; C099071:L 159884; D000803:Angiotensin I; C014055:methyl iodide