title: Synthesis and SAR of sulfoxide substituted carboxyquinolines as NK3 receptor antagonists.
abstract: The neurokinin-3 (NK3) receptor is regarded as a potential novel target for treating patients with schizophrenia. Herein we report the synthesis and SAR of a series of C3-alkylsulfoxide substituted quinolines as potent NK3 receptor antagonists. These compounds have excellent NK3 functional activity, good selectivity and drug-like properties. Several key compounds have good in vitro/in vivo DMPK characteristics, and are active in a gerbil locomotor activity model.
authors.affiliation: CNS Discovery, AstraZeneca Pharmaceuticals, Wilmington, DE, USA.
authors.forename: Hui
authors.initials: H
authors.lastname: Xiong
authors.forename: James
authors.initials: J
authors.lastname: Kang
authors.forename: James M
authors.initials: JM
authors.lastname: Woods
authors.forename: John P
authors.initials: JP
authors.lastname: McCauley
authors.forename: Gerard M
authors.initials: GM
authors.lastname: Koether
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Albert
authors.forename: Lindsay
authors.initials: L
authors.lastname: Hinkley
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.forename: Reto A
authors.initials: RA
authors.lastname: Gadient
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Simpson
mesh_terms: D000818:Animals; D005849:Gerbillinae; D009043:Motor Activity / Q000187:drug effects; D011804:Quinolines / Q000737:chemistry* / Q000494:pharmacology*; D018042:Receptors, Neurokinin-3 / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship; D013454:Sulfoxides / Q000737:chemistry*
chemical_list: D011804:Quinolines; D018042:Receptors, Neurokinin-3; D013454:Sulfoxides