RELATIONSHIP BETWEEN DIHEDRAL ANGLES OF N1 AND C9 SUBSTITUENTS IN 1,4-BENZODIAZEPINES AND DUAL CHOLECYSTOKININ-A AND CHOLECYSTOKININ-B ANTAGONISTIC ACTIVITIES

Introduction of a methyl moiety to the C9 position of a 1,4-benzodiaze pine ring system afforded dual CCK-A and -B antagonistic activity. Nov el derivatives having ethyl, isopropyl and chloro substituents at C9 w ere prepared in order to obtain more potent antagonistic activities. A M1(MOPAC93) calculations of the dihedral angles between the N1 and C9 substituents indicated that dihedral angles for dual antagonistic acti vities were between 50 degrees and 60 degrees. A methyl moiety was sel ected as the most suitable C9 substituent in this series for potent du al CCK-A and -B receptor antagonistic properties. (C) 1998 Elsevier Sc ience Ltd. All rights reserved.