Simple Coupling Reaction between Amino Acids and Weakly Nucleophilic Heteroaromatic Amines

摘要

The application of parallel synthesis to generate combinatorial libraries as an efficient means of creating pharmaceutical "druglike leads" has gained considerable interest.By accelerating the synthesis and screening of an ever larger number of synthetic analogues,combinatorial chemistry has greatly impacted the drug discovery process.Recently,we published results on combinatorial synthesis of N-acylthioureas and on parallel solution-phase synthesis of peptides and pseudopeptides of biological interest.Our goal was to prepare compounds that could be tested through high-throughput or medium-throughput screenings on various proteolytic enzymes involved in pathologies as different as HIV and HBV or neurodegenerative disorders,such as Alzheimer's disease.In our present research program on the development of new molecules as potential gamma-secretase inhibitors,we are interested in the solution-phase synthesis of a parallel library of new pseudopeptide derivatives bearing various weakly activated amino heteroaromatic moieties.