title: Synthesis and SAR of new 5-phenyl-3-ureido-1,5-benzodiazepines as cholecystokinin-B receptor antagonists.
abstract: A series of 5-phenyl-3-ureidobenzodiazepine-2,4-diones was synthesized and evaluated as cholecystokinin-B (CCK-B) receptor antagonists. Structure-activity relationship (SAR) studies revealed the importance of the N-1 substituent for potent and selective CCK-B affinity. Addition of substituents at the urea side chain provided in some cases more potent compounds. Moreover the introduction of bulky substituents such as adamantylmethyl at N-1 and resolution of the racemic ureas resulted in our lead compound GV150013.
authors.affiliation: Glaxo Wellcome Medicines Research Centre, Via A. Fleming 4, 37135 Verona, Italy. au4438@glaxowellcome.co.uk
authors.forename: A
authors.initials: A
authors.lastname: Ursini
authors.forename: A M
authors.initials: AM
authors.lastname: Capelli
authors.forename: R A
authors.initials: RA
authors.lastname: Carr
authors.forename: P
authors.initials: P
authors.lastname: Cassarà
authors.forename: M
authors.initials: M
authors.lastname: Corsi
authors.forename: O
authors.initials: O
authors.lastname: Curcuruto
authors.forename: G
authors.initials: G
authors.lastname: Curotto
authors.forename: M
authors.initials: M
authors.lastname: Dal Cin
authors.forename: S
authors.initials: S
authors.lastname: Davalli
authors.forename: D
authors.initials: D
authors.lastname: Donati
authors.forename: A
authors.initials: A
authors.lastname: Feriani
authors.forename: H
authors.initials: H
authors.lastname: Finch
authors.forename: G
authors.initials: G
authors.lastname: Finizia
authors.forename: G
authors.initials: G
authors.lastname: Gaviraghi
authors.forename: M
authors.initials: M
authors.lastname: Marien
authors.forename: G
authors.initials: G
authors.lastname: Pentassuglia
authors.forename: S
authors.initials: S
authors.lastname: Polinelli
authors.forename: E
authors.initials: E
authors.lastname: Ratti
authors.forename: A M
authors.initials: AM
authors.lastname: Reggiani
authors.forename: G
authors.initials: G
authors.lastname: Tarzia
authors.forename: G
authors.initials: G
authors.lastname: Tedesco
authors.forename: M E
authors.initials: ME
authors.lastname: Tranquillini
authors.forename: D G
authors.initials: DG
authors.lastname: Trist
authors.forename: F T
authors.initials: FT
authors.lastname: Van Amsterdam
authors.forename: A
authors.initials: A
authors.lastname: Reggiani
mesh_terms: D000818:Animals; D014151:Anti-Anxiety Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001569:Benzodiazepines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002144:Callithrix; D002540:Cerebral Cortex / Q000378:metabolism; D018360:Crystallography, X-Ray; D006168:Guinea Pigs; D006367:HeLa Cells; D006801:Humans; D066298:In Vitro Techniques; D008566:Membranes; D051379:Mice; D008958:Models, Molecular; D010179:Pancreas / Q000378:metabolism; D011869:Radioligand Assay; D051381:Rats; D043886:Receptor, Cholecystokinin A; D043887:Receptor, Cholecystokinin B; D011949:Receptors, Cholecystokinin / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D014151:Anti-Anxiety Agents; D043886:Receptor, Cholecystokinin A; D043887:Receptor, Cholecystokinin B; D011949:Receptors, Cholecystokinin; D001569:Benzodiazepines