title: Synthesis and in vitro evaluation of N-substituted aza-trozamicol analogs as vesicular acetylcholine transporter ligands.
abstract: As dysfunction of cerebral cholinergic neurotransmission is one of the main features in patients with Alzheimer's disease, in vivo imaging of the vesicular acetylcholine transporter (VAChT) can be of great value for the early diagnosis of this disease. Two series of positional isomers of m-iodobenzyltrozamicol (MIBT): 3-hydroxy-4-(N-phenylpiperazinyl)piperidine and 4-hydroxy-3-(N-phenylpiperazinyl)piperidine substituted by benzyl, aryl, alkyl or vinyl groups at the nitrogen have been synthesized. These compounds have been evaluated in vitro by competition studies and five compounds (N-benzyl derivatives) showed high affinity for the VAChT (11nM<IC(50)<66nM). These compounds will be soon radiolabeled with [(125)I] for further biological evaluation using single photon emission computed tomography (SPECT).
authors.affiliation: Université François-Rabelais de Tours, 37200 Tours, France.
authors.forename: Thaer
authors.initials: T
authors.lastname: Assaad
authors.forename: Sylvie
authors.initials: S
authors.lastname: Mavel
authors.forename: Stanley M
authors.initials: SM
authors.lastname: Parsons
authors.forename: Shane
authors.initials: S
authors.lastname: Kruse
authors.forename: Laurent
authors.initials: L
authors.lastname: Galineau
authors.forename: Hassan
authors.initials: H
authors.lastname: Allouchi
authors.forename: Michael
authors.initials: M
authors.lastname: Kassiou
authors.forename: Sylvie
authors.initials: S
authors.lastname: Chalon
authors.forename: Denis
authors.initials: D
authors.lastname: Guilloteau
authors.forename: Patrick
authors.initials: P
authors.lastname: Emond
mesh_terms: D000109:Acetylcholine / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism*; D008024:Ligands; D013329:Structure-Activity Relationship
chemical_list: D002352:Carrier Proteins; D008024:Ligands; D000109:Acetylcholine