1,2,5-Trisubstituted 1,4-diazepine-3-one: A novel dipeptidomimetic molecular scaffold
- 51 Downloads
The continuing effort to transform bioactive peptides into non-peptide peptidomimetics of therapeutic potential requires a diversity of tools such as molecular scaffolds, pseudopeptide modifications, and conformation mimetics. To this end, a novel polyfunctional monoheterocyclic system, 1,2,5-trisubstituted hexahydro-3-oxo-1H-1,4-diazepine ring (DAP), was designed. The linear precursor for the DAP was generated through a reductive alkylation step including a modified side chain and an α-amino function of two amino acid derivatives. Structural analysis of model diastereomeric DAPs, employing1H and13C NMR and computer simulation, revealed the conformational preferences of this system. The structural similarities to the 1,4-benzodiazepine, a common molecular scaffold for many non-peptidic peptidomimetic agents, and the pronounced dipeptidomimetic character of the DAP system offer a new powerful tool to medicinal chemists engaged in rational peptide-based drug design.
Key words1,4-diazepine-3-one dipeptidomimetic molecular scaffold
Unable to display preview. Download preview PDF.
- 4.a.Hölzemann, G., Kontakte (Darmstadt) 1 (1991) 3.Google Scholar
- 4.b.Hölzemann, G., Kontakte (Darmstadt) 2 (1991) 55.Google Scholar
- 5.Farmer, P.S., In Ariens, E.J. (Ed.) Drug Design, Vol. X, Academic Press, New York, NY, 1980, pp. 19–43.Google Scholar
- 9.Sawyer, T.K., In Taylor, M.D. and Amidon, G.L. (Eds.) Peptides-Based Drug Design Controlling Transport and Metabolism, American Chemical Society, Washington, DC, 1995, pp. 385–422, and references therein.Google Scholar