POTENT AND SUBTYPE-SELECTIVE CCK-B GASTRIN RECEPTOR ANTAGONISTS - 2,4-DIOXO-1,5-BENZODIAZEPINES WITH A PLANE OF SYMMETRY/

A series of CCK-B/gastrin receptor antagonists, 2,4-dioxo-1,5-benzodia zepine derivatives with a plane of symmetry, were designed, synthesize d, and evaluated for antagonistic activity. Structure-activity relatio nship studies revealed that carbonylmethyl groups at both N-1 and N-5 positions and hydrophilic groups, such as the carboxyl group on the be nzene ring attached to the ureido group at the C-3 position, brought a bout potent affinity and subtype selectivity for CCK-B/gastrin recepto rs. Several compounds showed excellent in vivo inhibition of gastric a cid secretion induced by pentagastrin in anesthetized rats. (C) 1997 E lsevier Science Ltd.