Synthesis and in vivo evaluation of [11C]semotiadil, a benzothiazine calcium antagonist.
A carbon-11 labeled benzothiazine calcium antagonist, (+)-(R)-2-[5-methoxy-2-[3-[methyl[2-[(3,4- methylenedioxy)phenoxy]ethyl]amino]propoxy]phenyl]-4-methyl-2H-1,4- benzothiazin-3(4H)-one (semotiadil), and its enantiomer were prepared by N-methylation of the corresponding norderivatives with 11CH3I: decay-corrected radiochemical yields of 16-27% based on 11CH3I, radiochemical, chemical and optical purity of > 99%, sp. act. of 11-50 GBq/mumol and preparation time of 35-40 min. In mice, saturable and stereo-selective uptake in the hippocampus, striatum and hypothalamus was observed. The potential of the compound to visualize the regional brain calcium channels in vivo by positron emission tomography was indicated; however, no promising sign was found in the myocardium.
Ishiwata
K
K
Positron Medical Center, Tokyo Metropolitan Institute of Gerontology, Japan.
Seki
H
H
Ishii
K
K
Ishii
S
S
Nozaki
T
T
Senda
M
M
D000818:Animals; D002121:Calcium Channel Blockers / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D002250:Carbon Radioisotopes; D003342:Corpus Striatum / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism; D007031:Hypothalamus / Q000378:metabolism; D008297:Male; D051379:Mice; D013844:Thiazoles / Q000138:chemical synthesis* / Q000493:pharmacokinetics
D002121:Calcium Channel Blockers; D002250:Carbon Radioisotopes; D013844:Thiazoles; C064356:sesamodil