The combinatorial synthesis and chemical and biological evaluation of a 1,4-benzodiazepine library.
A library of 192 structurally diverse 1,4-benzodiazepine derivatives containing a variety of chemical functionalities including amides, carboxylic acids, amines, phenols, and indoles was constructed from three components, 2-aminobenzophenones, amino acids, and alkylating agents, by employing Geysen's pin apparatus [Geysen, H. M., Rodda, S. J., Mason, T. J., Tribbick, G. & Schoofs, P. G. (1987) J. Immunol. Methods 102, 259-274]. Rigorous analytical verification of the chemical integrity and yield of a representative collection of the diverse derivatives was carried out. In addition, the library of derivatives was evaluated for binding to the cholecystokinin A receptor by employing a competitive radio-ligand binding assay. This provided detailed structure versus activity relationships that were confirmed by independent large-scale synthesis and evaluation of several of the 1,4-benzodiazepine derivatives.
Bunin
B A
BA
Department of Chemistry, University of California at Berkeley 94720.
Plunkett
M J
MJ
Ellman
J A
JA
D000595:Amino Acid Sequence; D000818:Animals; D001569:Benzodiazepines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D001667:Binding, Competitive; D008969:Molecular Sequence Data; D051381:Rats; D013329:Structure-Activity Relationship
D001569:Benzodiazepines