4-(4-fluorobenzoyl)-1-[2-(4-iodo-2,5-dimethoxyphenyl)ethyl]piperidine and its derivatives: synthesis and affinity at 5-HT2A, 5-HT2B and 5-HT2C serotonin receptors

4-(4-Fluorobenzoyl)-1-[2-(4-iodo-2,5-dimethoxyphenyl)ethyl]piperidine (7) a nd its derivatives modified at the carbonyl group of the fluorobenzoyl moie ty were prepared and evaluated for affinity at 5-HT2A, 5-HT2C (rat cortex) and 5-HT2B (rat stomach fundus) serotonin receptors. Compound 7 bound the 5 -HT2A sites with higher affinity (K-i = 8.2 nM) than the 5-HT2B (K-b = 1 29 0 nM) and 5-HT2C ones (K-i = 54.2 nM). Modification of the benzoyl carbonyl group decreased the 5-HT2A and 5-HT2C affinities but did not significantly influence 5-HT2B affinity. This suggests that the carbonyl group is the de terminant for the interaction with 5-HT2A and 5-HT2C receptor subtypes. Com pound 7 was found to be a 5-HT2A receptor antagonist. (C) 1999 Editions sci entifiques et medicales Elsevier SAS.