The combinatorial synthesis and chemical and biological evaluation of a 1,4-benzodiazepine library.
- 24 May 1994
- journal article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences
- Vol. 91 (11) , 4708-4712
- https://doi.org/10.1073/pnas.91.11.4708
Abstract
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.Keywords
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