title: Synthesis and structure-activity relationship of new 1,5-dialkyl-1,5-benzodiazepines as cholecystokinin-2 receptor antagonists.
abstract: This article deals with the synthesis and the activities of some 1,5-dialkyl-3-arylureido-1,5-benzodiazepin-2,4-diones which were prepared as potential CCK2 antagonists, with the intention to find a possible follow up of our lead compound GV150013, showing an improved pharmacokinetic profile. The phenyl ring at N-5 was replaced with more hydrophilic substituents, like alkyl groups bearing basic functions. In some cases, the resolution of the racemic key intermediates 3-amino-benzodiazepines was also accomplished. Among the compounds synthesized and characterised so far in this class, the 5-morpholinoethyl derivative 54, was selected as potential follow up of GV150013 and submitted for further evaluation.
authors.affiliation: GlaxoSmithKline, Medicines Research Centre, Via A. Fleming, 4, 37100 Verona, Italy. karen.l.roberts@gsk.com
authors.forename: Karen
authors.initials: K
authors.lastname: Roberts
authors.forename: Antonella
authors.initials: A
authors.lastname: Ursini
authors.forename: Robert
authors.initials: R
authors.lastname: Barnaby
authors.forename: Paolo G
authors.initials: PG
authors.lastname: Cassarà
authors.forename: Mauro
authors.initials: M
authors.lastname: Corsi
authors.forename: Giovanni
authors.initials: G
authors.lastname: Curotto
authors.forename: Daniele
authors.initials: D
authors.lastname: Donati
authors.forename: Aldo
authors.initials: A
authors.lastname: Feriani
authors.forename: Gabriella
authors.initials: G
authors.lastname: Finizia
authors.forename: Carla
authors.initials: C
authors.lastname: Marchioro
authors.forename: Daniela
authors.initials: D
authors.lastname: Niccolai
authors.forename: Beatrice
authors.initials: B
authors.lastname: Oliosi
authors.forename: Stefano
authors.initials: S
authors.lastname: Polinelli
authors.forename: Emiliangelo
authors.initials: E
authors.lastname: Ratti
authors.forename: Angelo
authors.initials: A
authors.lastname: Reggiani
authors.forename: Giovanna
authors.initials: G
authors.lastname: Tedesco
authors.forename: Maria E
authors.initials: ME
authors.lastname: Tranquillini
authors.forename: David G
authors.initials: DG
authors.lastname: Trist
authors.forename: Franciscus T M
authors.initials: FT
authors.lastname: van Amsterdam
mesh_terms: D000818:Animals; D001570:Benzodiazepinones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004285:Dogs; D006168:Guinea Pigs; D051379:Mice; D015394:Molecular Structure; D051381:Rats; D043887:Receptor, Cholecystokinin B / Q000037:antagonists & inhibitors*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D014018:Tissue Distribution
chemical_list: D001570:Benzodiazepinones; D043887:Receptor, Cholecystokinin B