Synthesis and SAR of new 5-phenyl-3-ureido-1,5-benzodiazepines as cholecystokinin-B receptor antagonists

Authors
Ursini, A Capelli, AM Carr, RAE Cassara, P Corsi, M Curcuruto, O Curotto, G Dal Cin, M Davalli, S Donati, D Feriani, A Finch, H Finizia, G Gaviraghi, G Marien, M Pentassuglia, G Polinelli, S Ratti, E Reggiani, A Tarzia, G Tedesco, G Tranquillini, ME Trist, DG Van Amsterdam, FTM
Citation
A. Ursini et al., Synthesis and SAR of new 5-phenyl-3-ureido-1,5-benzodiazepines as cholecystokinin-B receptor antagonists, J MED CHEM, 43(20), 2000, pp. 3596-3613
Citations number
44
Categorie Soggetti
Chemistry & Analysis
Journal title
JOURNAL OF MEDICINAL CHEMISTRY
ISSN journal
00222623 → ACNP
Volume
43
Issue
20
Year of publication
2000
Pages
3596 - 3613
Database
ISI
SICI code
0022-2623(20001005)43:20<3596:SASON5>2.0.ZU;2-F
Abstract
A series of 5-phenyl-3-ureidobenzodiazepine-2,4-diones was synthesized and evaluated as cholecystokinin-B (CCK-B) receptor antagonists. Structure-acti vity relationship (SAR) studies revealed the importance of the N-1 substitu ent for potent and selective CCK-B affinity. Addition of substituents at th e urea side chain provided in some cases more potent compounds. Moreover th e introduction of bulky substituents such as adamantylmethyl at; N-1 and re solution of the racemic ureas resulted in our lead compound GV150013.