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

Ursini, A; Capelli, A M; Carr, R A; Cassarà, 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 M; Tarzia, G; Tedesco, G; Tranquillini, M E; Trist, D G; Van Amsterdam, F T; Reggiani, A.

J Med Chem ; 43(20): 3596-613, 2000 Oct 05.

Article in English | MEDLINE | ID: mdl-11020274

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.

Subject(s)

Anti-Anxiety Agents/chemical synthesis , Benzodiazepines/chemical synthesis , Receptors, Cholecystokinin/antagonists & inhibitors , Animals , Anti-Anxiety Agents/chemistry , Anti-Anxiety Agents/pharmacology , Benzodiazepines/chemistry , Benzodiazepines/pharmacology , Callithrix , Cerebral Cortex/metabolism , Crystallography, X-Ray , Guinea Pigs , HeLa Cells , Humans , In Vitro Techniques , Membranes , Mice , Models, Molecular , Pancreas/metabolism , Radioligand Assay , Rats , Receptor, Cholecystokinin A , Receptor, Cholecystokinin B , Receptors, Cholecystokinin/metabolism , Stereoisomerism , Structure-Activity Relationship

Novel 1,5-benzodiazepines as CCK-B ligands. Effect of aryl-carbamic substituents at the C-3 position together with halogen substitution on the benzo-fused ring.

Tranquillini, M E; Cassarà, P G; Corsi, M; Curotto, G; Donati, D; Finizia, G; Pentassuglia, G; Polinelli, S; Tarzia, G; Ursini, A; van Amsterdam, F T.

Arch Pharm (Weinheim) ; 330(11): 353-7, 1997 Nov.

Article in English | MEDLINE | ID: mdl-9431027

Subject(s)

Benzodiazepines/chemical synthesis , Benzodiazepines/metabolism , Hydrocarbons, Halogenated/chemical synthesis , Hydrocarbons, Halogenated/metabolism , Receptors, Cholecystokinin/metabolism , Animals , Benzodiazepines/pharmacology , Guinea Pigs , Hydrocarbons, Halogenated/pharmacology , Kinetics , Ligands , Receptor, Cholecystokinin B , Stereoisomerism , Structure-Activity Relationship

ABSTRACT

Subject(s)

Subject(s)

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