THE BIOLOGICALLY ACTIVE CONFORMATION OF IMIDAZO- LINONE AMINO ACIDS AT GLYCINE RECEPTOR

J.Karolak-Wojciechowskal, K.Kieè-Kononowicz2

1Institute o.f' General and Ecological Chemistry, Technical University, 90-924 Lódž, Poland;
2 Department of' Chemical Techn. of' Drugs, Jagiellonian University, 30-ó88 Kraków, Poland.

The structure-activity studies of CNS agents for long time were hampered by the lack of the information regarding the target site for the drug. However thanks to recent development of new powerful tools for drug design and also the progress in the knowledge of the CNS receptors, the search for compounds, which selectively affect one type of CNS receptor, has become more rational basing on topological and for stereochemical requirements for a single receptor.

The basic model for the glycine receptor site has been well documented. However, the compound reported as ligands of glycine receptor [1] incorporated spatially inflexible amino acid moiety and the binding for glycine site was limited to one bioactive conformation. The series of the presented by us arylidene- imidazolinone with confirmed affnity to the receptor [2] consist of amino acidic chain with rotational freedom. The amino acid moiety may have several allowable conformations. Not all of them fulfill stereochemical criteria for binding. Therefore, the role of an amino acid glycine chain in the formation of a complex with receptor is definitely not yet clear.

We solved the structures of the representative compounds from the title class and on that base we preperd the conformational analysis of the arylideneimidazolinone amino acid chain with respect to topographical requirements of the glycine receptor [1]. It was realized by molecular modeling, quantum chemical calculations and structures correlation method

  1. Leeson,P.D.,Iversen,L.L; J.Med.Chem., 37, 4053-4067,1994.
  2. Kieè-Kononowicz,K.,Karolak-Wojciechowska,J., in preparation,1998,
  3. Allen F.H., Kennard O., Taylor, Acc. Chem.Res.,16,146-153,1983

This stuïy was supported by Polish State Committee for Scientific Research (kBN), grant no 4 POSF 00310.