MK-329 - A NONPEPTIDE CHOLECYSTOKININ-A ANTAGONIST

Peptide receptors represent important targets for a variety of potentially important disease modifying drugs. Over the past 20 years, considerable effort has been spent on modifying the natural ligands for peptide receptors, the peptides themselves, with limited success. Using a targeted screen, namely cholecystokinin (CCK)-A receptor binding, the Merck group in 1984 discovered asperlicin, a potent non-peptide cholecystokinin antagonist selective for peripheral tissues, that was isolated from Aspergillus alliaceaus. This compound was used as a lead to develop MK-329, a CCK-A receptor antagonist, the evolution of which is discussed within the context of the drug discovery process and receptor modeling strategies. (C) 1993 Wiley-Liss, Inc.