Synthesis and amine transporter affinities of novel phenyltropane derivatives as potential positron emission tomography (PET) imaging agents.
A series of novel fluoroalkyl-containing tropane derivatives (6-8, 10-14, 17, and 18) were synthesized from cocaine. Novel compounds were evaluated for affinity and selectivity in competitive radioligand binding assays selective for cerebral serotonin (5-HT), dopamine (DA), and norepinephrine (NE) transporters (SERT, DAT, and NET). The nortropane-fluoroalkyl esters (7, 10, 11) were most potent for SERT (K(i): 0.18, 0.24, and 0.30 nM, respectively). Tosylate esters 17 and 18, synthesized as precursors for [(18)F]-labeled, Positron Emission Tomography (PET) imaging agents, also showed high affinity for DAT.
Medicinal Chemistry Laboratory, Alcohol and Drug Abuse Research Center, McLean Hospital, Harvard Medical School, 115 Mill Street, Belmont, MA 02478-9106, USA.
Xuemei
X
Peng
Ao
A
Zhang
Nora S
NS
Kula
Ross J
RJ
Baldessarini
John L
JL
Neumeyer
D000818:Animals; D001667:Binding, Competitive; D001679:Biogenic Amines / Q000378:metabolism; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002352:Carrier Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015394:Molecular Structure; D049268:Positron-Emission Tomography / Q000379:methods*; D011869:Radioligand Assay; D051381:Rats; D013329:Structure-Activity Relationship; D014326:Tropanes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology
D001679:Biogenic Amines; D002352:Carrier Proteins; D014326:Tropanes