128255-00-5Relevant academic research and scientific papers
Arylcarbamate derivatives of 1-piperidineethanol as potent ligands for 5-HT4 receptors
Soulier, Jean-Louis,Yang, Donglai,Brémont, Béatrice,Croci, Tiziano,Guzzi, Umberto,Langlois, Michel
, p. 1755 - 1761 (2007/10/03)
A series of carbamate derivatives (7) of 2-(1-piperidinyl)ethyl 4- amino-5-chloro-2-methoxybenzoates, which have been described as potent agonists and antagonists of 5-HT4 receptors, were synthesized. They were evaluated using radioligand binding assays with [3H]GR 113808, a 5-HT4 receptor selective ligand, in the rat striatum and the electrically stimulated myenteric plexus longitudinal muscle of the guinea pig. In contrast to the previously described ester derivatives, a drop in the affinity for 5-HT4 receptors was observed and the compounds were inactive as agonists in the guinea pig ileum preparation. Unexpectedly, the ortho- substituted carbamates 8b,c (R' = H, RO = MeO or EtO, R'' = H) had nanomolar affinity for 5-HT4 receptors (K(i) = 8.9 ± 0.5 and 2.6 ± 0.4 nM, respectively). As reported previously, the cis- or trans-3,5-dimethyl substitution of piperidine (8n,o) was particularly favorable (K(i) = 1.1 ± 0.6 nM for both isomers). 8c is an antagonist equipotent to the 5-HT4 receptor antagonist SDZ 205-557 (1).
