title: Parallel solid-phase synthesis and characterization of new sulfonamide and carboxamide proline derivatives as potential CNS agents.
abstract: A solid-phase synthesis of the 64-member library of novel sulfonamide and carboxamide proline derivatives, focused on the 5-HT7 receptor antagonist SB-258741, was described. The final compounds were obtained in good yields and high purity upon cleavage from SynPhase Lanterns, functionalized by a BAL linker. The library representatives were screened for 5-HT7, 5-HT1A and D2 receptors to explore the impact of a tertiary amine moiety, the length of an alkylene spacer and the aryl fragment on the receptor affinity. The preliminary biological results provided data for further investigation aimed at a search for 5-HT7 receptor agents, and permitted the identification of several compounds with significant 5-HT1A receptor affinity.
authors.affiliation: Laboratoire des Aminoacides, Peptides et Protéines (LAPP), UMR 5810, Faculté de Pharmacie, Université Montpellier I et II, 15 avenue Charles Flahault, 34060 Montpellier, France. mfzajdel@cyf-kr.edu.pl
authors.forename: Paweł
authors.initials: P
authors.lastname: Zajdel
authors.forename: Gilles
authors.initials: G
authors.lastname: Subra
authors.forename: Andrzej J
authors.initials: AJ
authors.lastname: Bojarski
authors.forename: Beata
authors.initials: B
authors.lastname: Duszyńska
authors.forename: Maciej
authors.initials: M
authors.lastname: Pawłowski
authors.forename: Jean
authors.initials: J
authors.lastname: Martinez
mesh_terms: D000577:Amides / Q000737:chemistry*; D001667:Binding, Competitive / Q000187:drug effects; D002491:Central Nervous System Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D008024:Ligands; D015394:Molecular Structure; D010880:Piperidines / Q000494:pharmacology; D011392:Proline / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000494:pharmacology; D011759:Pyrrolidines / Q000494:pharmacology; D011869:Radioligand Assay; D044282:Receptor, Serotonin, 5-HT1A / Q000187:drug effects; D011954:Receptors, Dopamine / Q000187:drug effects; D011985:Receptors, Serotonin / Q000187:drug effects; D013449:Sulfonamides / Q000737:chemistry*; D014105:Tosyl Compounds / Q000494:pharmacology
chemical_list: D000577:Amides; D002491:Central Nervous System Agents; D008024:Ligands; D010880:Piperidines; D011759:Pyrrolidines; D011954:Receptors, Dopamine; D011985:Receptors, Serotonin; C462239:SB258741; D013449:Sulfonamides; D014105:Tosyl Compounds; C104425:serotonin 7 receptor; D044282:Receptor, Serotonin, 5-HT1A; D011392:Proline