Simplified analogues of ritanserin and their affinity at 5-HT(2A), 5- HT(2B) and 5-HT(2C) serotonin receptors

Article abstract of DOI:10.1016/S0223-5234(98)80029-9

The 5-HT₂ serotonin antagonist ritanserin (6-(2-[4-[bis(4- fluorophenyl)methylene]-l-piperidinyl]ethyl)-7-methyl-5H-thiazole[3,2- a]pyrimidin-5-one, 2) binds with high affinity to 5-HT(2A), 5-HT(2B) and 5- HT(2C) serotonin receptors. With the aim of exploring how simplification of the thiazolepyrimidinone nucleus of 2 affects the affinity and selectivity for 5-HT(2A), 5-HT(2B) and 5-HT(2C) subtypes, some derivatives of 4-[bis(4- fluorophenyl)methylene]piperidine were synthesized, and their 5-HT(2A) and 5- HT(2C) receptor binding affinities and 5-HT(2B) antagonistic affinity evaluated. The new compounds bind the three 5-HT₂ subtypes with lower affinity than did 2. Simplification of the thiazolepyrimidinone nucleus of ritanserin has only slight influence on the selectivity for 5-HT₂ subtypes. The results suggest that the thiazolepyrimidinone moiety participates in key binding interactions and is determinant for high affinity at 5-HT₂ receptor subtypes. Some derivatives showed antagonistic activity at 5-HT(2A) receptor.