Synthesis and structure–activity relationship studies in serotonin 5-HT4 receptor ligands based on a benzo[de][2,6]naphthridine scaffold

• Published in: European journal of medicinal chemistry Vol. 82; pp. 36 - 46
• Main Authors: Castriconi, Federica, Paolino, Marco, Giuliani, Germano, Anzini, Maurizio, Campiani, Giuseppe, Mennuni, Laura, Sabatini, Chiara, Lanza, Marco, Caselli, Gianfranco, De Rienzo, Francesca, Menziani, Maria Cristina, Sbraccia, Maria, Molinari, Paola, Costa, Tommaso, Cappelli, Andrea
• Format: Journal Article
• Language: English
• Published: ISSY-LES-MOULINEAUX Elsevier Masson SAS 23.07.2014; Elsevier
• Subjects: 5-HT4 receptor ligands; Animals; Chemistry, Medicinal; Crystallography, X-Ray; Dose-Response Relationship, Drug; G-protein coupled receptor; Guinea Pigs; Life Sciences & Biomedicine; Ligands; Male; Models, Molecular; Molecular modelling; Molecular Structure; Naphthyridines - chemical synthesis; Naphthyridines - chemistry; Naphthyridines - pharmacology; Pharmacology & Pharmacy; Receptors, Serotonin, 5-HT4 - metabolism; Science & Technology; Serotonin; Serotonin 5-HT4 Receptor Agonists - chemical synthesis; Serotonin 5-HT4 Receptor Agonists - chemistry; Serotonin 5-HT4 Receptor Agonists - pharmacology; Structure-Activity Relationship; Synthesis; BRET; 5-HT4 receptor ligands; AD; Serotonin; 5-HT4R; sAPPα; GFP; GERD; Synthesis; Molecular modelling; CV; G-protein coupled receptor; GPCRs; IBS; 5-HT; SITE; COMPLEX; ACETYLCHOLINE; GUINEA-PIG; AGONISTS; BENZAMIDE DERIVATIVES; POTENT; PROFILE; ANTAGONISTS

A small series of serotonin 5-HT4 receptor ligands has been designed from flexible 2-methoxyquinoline compounds 7a,b by applying the conformational constraint approach. Ligands 7a,b and the corresponding conformationally constrained analogues 8a–g were synthesized and their interactions with the 5-H...