The 5-HT, serotonin antagonist ritanserin (6-I 2-(4-(bis(4-Auorophenyl)methylene~-l-piperidinyI~ethyl]-7-methyl-5HthiazoIe[ 3,2-a]pyrimidin-5-one, 2) binds with high affinity to 5-HT,,, 5-HT,, and 5-HT,, serotonin receptors. With the aim of exploring how simplification of the thiazolepyrimidinone nucleus of 2 affects the affmity and se’rectifvity for MIT,,, 5-HT,, and 5-HT, subtypes, some derivatives of 4-[bis(4-fluorophenyl)methylene]piperidine were synthesized, and their .5-HT,, and 5-HT,, receptor binding affinities and 5-HT,, antagonistic affinity evaluated. The new compounds bind the three 5-HT, subtypes with lower affinity than did 2. Simplification of the thiazolepyrimidinone nucleus of ritanserin has only slight influence on the selectivity for 5-HT, subtypes. The results suggest that the thiazolepyrimidinone moiety participates in key binding interactions and is determinant for high affinity at 5-HT, receptor subtypes. Some derivatives showed antagonistic activity at S-HT,, receptor.
Simplified analogues of ritanserin and their affinity at 5HT2A, 5HT2B and 5HT2C serotonin receptors
GESSI, Stefania;SINISCALCHI, Anna;BOREA, Pier Andrea
1998
Abstract
The 5-HT, serotonin antagonist ritanserin (6-I 2-(4-(bis(4-Auorophenyl)methylene~-l-piperidinyI~ethyl]-7-methyl-5HthiazoIe[ 3,2-a]pyrimidin-5-one, 2) binds with high affinity to 5-HT,,, 5-HT,, and 5-HT,, serotonin receptors. With the aim of exploring how simplification of the thiazolepyrimidinone nucleus of 2 affects the affmity and se’rectifvity for MIT,,, 5-HT,, and 5-HT, subtypes, some derivatives of 4-[bis(4-fluorophenyl)methylene]piperidine were synthesized, and their .5-HT,, and 5-HT,, receptor binding affinities and 5-HT,, antagonistic affinity evaluated. The new compounds bind the three 5-HT, subtypes with lower affinity than did 2. Simplification of the thiazolepyrimidinone nucleus of ritanserin has only slight influence on the selectivity for 5-HT, subtypes. The results suggest that the thiazolepyrimidinone moiety participates in key binding interactions and is determinant for high affinity at 5-HT, receptor subtypes. Some derivatives showed antagonistic activity at S-HT,, receptor.I documenti in SFERA sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
