title: Highly potent, non-basic 5-HT6 ligands. Site mutagenesis evidence for a second binding mode at 5-HT6 for antagonism.
abstract: A series of 5-HT(6) ligands derived from (R)-1-(amino)methyl-6-(phenyl)sulfonyltetralin was prepared that yielded several non-basic analogs having sub-nanomolar affinity. Ligand structure-activity relationships, receptor point mutation studies, and molecular modeling of these novel ligands all combined to reveal a new alternative binding mode to 5-HT(6) for antagonism.
authors.affiliation: Roche Palo Alto LLC, 3431 Hillview Ave., Palo Alto, CA 94304, USA.
authors.forename: Ralph N
authors.initials: RN
authors.lastname: Harris
authors.forename: Russel S
authors.initials: RS
authors.lastname: Stabler
authors.forename: David B
authors.initials: DB
authors.lastname: Repke
authors.forename: James M
authors.initials: JM
authors.lastname: Kress
authors.forename: Keith A
authors.initials: KA
authors.lastname: Walker
authors.forename: Renee S
authors.initials: RS
authors.lastname: Martin
authors.forename: Julie M
authors.initials: JM
authors.lastname: Brothers
authors.forename: Mariola
authors.initials: M
authors.lastname: Ilnicka
authors.forename: Simon W
authors.initials: SW
authors.lastname: Lee
authors.forename: Tara
authors.initials: T
authors.lastname: Mirzadegan
mesh_terms: D008024:Ligands; D008958:Models, Molecular; D016297:Mutagenesis, Site-Directed; D011985:Receptors, Serotonin / Q000378:metabolism*; D013329:Structure-Activity Relationship
chemical_list: D008024:Ligands; D011985:Receptors, Serotonin; C097216:serotonin 6 receptor