131741-82-7Relevant academic research and scientific papers
Simplified analogues of ritanserin and their affinity at 5-HT(2A), 5- HT(2B) and 5-HT(2C) serotonin receptors
Claudi, Francesco,Scoccia, Loredana,Giorgioni, Gianfabio,Marucci, Gabriella,Di Stefano, Antonio,Gessi, Stefania,Siniscalchi, Anna,Borea, Pier Andrea
, p. 705 - 713 (2007/10/03)
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.
3-[2-[4-(4-Fluorobenzoyl)piperidin-1-yl]ethyl]- 5,6,7,8-tetrahydro-4(3H)-quinazolinones: Serotonin 5-HT(2A) receptor antagonists endowed with potent central action
Claudi,Giorgioni,Scoccia,Ciccocioppo,Panocka,Massi
, p. 651 - 659 (2007/10/03)
A series of 5,6,7,8-tetrahydro-4(3H)-quinazolinones substituted at the 3-position with 4-benzoyl-1-ethylpiperidine, 4-(4-fluorobenzoyl)-1-ethylpiperidine, 4-[bis-(4-fluorophenyl)methylene]-1-ethylpiperidine, or 4-(4-fluorophenyl)-1-propylpiperazine have been prepared and evaluated in binding assays to determine their affinity at serotonin 5-HT(2A) receptors as well as in a functional test, ie, wet dog shakes (WDS) induced by L-5-hydroxytryptophan (L-5-HTP), a behavioural response which is mediated by stimulation of 5-HT(2A) receptors. Among the compounds prepared, 3-[2-[4-(4-fluorobenzoyl)piperidin-1-yl]ethyl]-5,6,7,8-tetrahydro-4(3H) -quinazolinone (10a) and 2-methyl-3-[2-[4-(4-fluorobenzoyl)piperidin-1-yl]ethyl]-5,6,7,8-tetrahydro -4(3H)-quinazolinone (10b) proved to be the most potent 5-HT(2A) receptor antagonists. In binding assays, the two compounds displayed similar affinity for 5-HT(2A) receptors in the nanomolar range to ketanserin and ritanserin. In the WDS test, they were even more potent than ketanserin and ritanserin. Compound 10b, which was found to possess the highest potency and duration of action in the WDS test, was chosen for a preliminary evaluation of its ability to inhibit ethanol intake in rats, a response linked to blockade of the central 5-HT(2A) receptors. This compound significantly reduced ethanol intake in rats from the first day of treatment. The results of the present study indicate that 10b is a potent centrally acting antagonist at 5-HT(2A), receptors.
