title: Identification and optimisation of novel sulfonamide, selective vasopressin V1B receptor antagonists.
abstract: The synthesis and preliminary structure-activity relationships (SAR) of a novel class of vasopressin V(1B) receptor antagonists are described. Hit compound 5, identified via high throughput screening of the corporate collection, showed good activity in a V(1B) binding assay (K(i) 63 nM) but did not possess the lead-like physicochemical properties typically required in a hit compound. A 'deletion approach' on the HTS hit 5 was performed, with the focus on improvement of physicochemical properties, yielding the selective V(1B) antagonist 9f (K(i) 190 nM), with improved druglike characteristics.
authors: Department of Pharmacology, MSD, Newhouse, Motherwell, United Kingdom.
authors: James
authors: J
authors: Baker
authors: Matilda
authors: M
authors: Bingham
authors: Ruth
authors: R
authors: Blackburn-Munro
authors: Jiaqiang
authors: J
authors: Cai
authors: Mark
authors: M
authors: Craighead
authors: Robert
authors: R
authors: Gilfillan
authors: Kate
authors: K
authors: Goan
authors: David
authors: D
authors: Jaap
authors: Rachel
authors: R
authors: Milne
authors: J Richard
authors: JR
authors: Morphy
authors: Susan
authors: S
authors: Napier
authors: Jeremy
authors: J
authors: Presland
authors: Gayle
authors: G
authors: Spinks
authors: Fiona
authors: F
authors: Thomson