2-Oxopyrrolidines and 6-oxoperhydropyrrolo[1,2-a]pyrazines as templates in the search for nonpeptide cholecystokinin ligands

Article abstract of DOI:10.1248/cpb.46.782

In order to find new classes of non-peptide cholecystokinin (CCK) ligands, the conformational restriction of a series of weak 3- oxoindolizidine-based CCK antagonists has been both decreased and increased. This tactic yielded a series of monocyclic 2-oxopyrrolidine derivatives 4 with selectivity for CCK-A or CCK-B receptors and with slightly improved binding affinity at the CCK-A receptor subtype with respect to the model 3- oxoindolizidines. In contrast, the incorporation of the Trp residue at the secondary amino group of a pyrrolo[1,2-a]pyrazine template 5, involving a drastic restriction in the conformational flexibility of the molecule, resulted in a series of bicyclic derivatives that did not bind to CCK receptors at concentrations up to 10^-5 M.

Full text of DOI:10.1248/cpb.46.782

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