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ID: ALA1135426

Journal: J Med Chem

Title: Synthesis, receptor potency, and selectivity of halogenated diphenylpiperidines as serotonin 5-HT2A ligands for PET or SPECT brain imaging.

Authors: Fu X, Tan PZ, Kula NS, Baldessarini R, Tamagnan G, Innis RB, Baldwin RM.

Abstract: A series of 4'-substituted phenyl-4-piperidinylmethanol and benzoyl-4-piperidine derivatives was synthesized as potential novel serotonin 5-HT2A receptor ligands that can be radiolabeled for in vivo brain imaging. Compounds were prepared by alkylation of 4-substituted benzoyl-4-piperidine with an iodo- or fluoro-substituted phenylalkyl halide followed by reduction with sodium borohydride. Potency of novel compounds was determined by in vitro radioreceptor affinity assays selective for serotonin 5-HT2A receptors. Potent compounds were further evaluated for selectivity at serotonin-2A versus 2C, 6, and 7, as well as dopamine D2 and adrenergic alpha1 and alpha2 receptors. The novel compound (4-fluorophenyl)-(1-[2-(4-fluorophenyl)ethyl]piperidin-4-yl])methanol was particularly promising with high 5-HT2A potency (K(i) = 1.63 nM) and >300-fold selectivity over other 5-HT receptor types.

CiteXplore: 12014970

DOI: 10.1021/jm0200411