title: Synthesis and SAR studies of novel 2-(4-oxo-2-aryl-quinazolin-3(4H)-yl)acetamide vasopressin V1b receptor antagonists.
abstract: Synthesis and structure-activity relationships (SAR) of a novel series of vasopressin V(1b) (V(3)) antagonists are described. 2-(4-Oxo-2-aryl-quinazolin-3(4H)-yl)acetamides have been identified with low nanomolar affinity for the V(1b) receptor and good selectivity with respect to related receptors V(1a), V(2) and oxytocin (OT). Optimised compound 12j demonstrates a good pharmacokinetic profile and activity in a mechanistic model of HPA dysfunction.
authors.affiliation: Department of Chemistry, MSD, Newhouse, Lanarkshire, UK. susannapier67@googlemail.com
authors.forename: Susan E
authors.initials: SE
authors.lastname: Napier
authors.forename: Jeffrey J
authors.initials: JJ
authors.lastname: Letourneau
authors.forename: Nasrin
authors.initials: N
authors.lastname: Ansari
authors.forename: Douglas S
authors.initials: DS
authors.lastname: Auld
authors.forename: James
authors.initials: J
authors.lastname: Baker
authors.forename: Stuart
authors.initials: S
authors.lastname: Best
authors.forename: Leigh
authors.initials: L
authors.lastname: Campbell-Wan
authors.forename: Jui-Hsiang
authors.initials: JH
authors.lastname: Chan
authors.forename: Mark
authors.initials: M
authors.lastname: Craighead
authors.forename: Hema
authors.initials: H
authors.lastname: Desai
authors.forename: Katharine A
authors.initials: KA
authors.lastname: Goan
authors.forename: Koc-Kan
authors.initials: KK
authors.lastname: Ho
authors.forename: Ellen G J
authors.initials: EG
authors.lastname: Hulskotte
authors.forename: Cliona P
authors.initials: CP
authors.lastname: MacSweeney
authors.forename: Rachel
authors.initials: R
authors.lastname: Milne
authors.forename: J Richard
authors.initials: JR
authors.lastname: Morphy
authors.forename: Irina
authors.initials: I
authors.lastname: Neagu
authors.forename: Michael H J
authors.initials: MH
authors.lastname: Ohlmeyer
authors.forename: Ard W M M
authors.initials: AW
authors.lastname: Peeters
authors.forename: Jeremy
authors.initials: J
authors.lastname: Presland
authors.forename: Chris
authors.initials: C
authors.lastname: Riviello
authors.forename: Ge S F
authors.initials: GS
authors.lastname: Ruigt
authors.forename: Fiona J
authors.initials: FJ
authors.lastname: Thomson
authors.forename: Heather A
authors.initials: HA
authors.lastname: Zanetakos
authors.forename: Jiuqiao
authors.initials: J
authors.lastname: Zhao
authors.forename: Maria L
authors.initials: ML
authors.lastname: Webb
mesh_terms: D000818:Animals; D065092:Antidiuretic Hormone Receptor Antagonists; D006801:Humans; D011799:Quinazolines / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D051381:Rats; D013329:Structure-Activity Relationship
chemical_list: D065092:Antidiuretic Hormone Receptor Antagonists; D011799:Quinazolines