Weiss, Stefan and Keller, Max and Bernhardt, Guenther and Buschauer, Armin and Koenig, Burkhard (2008) Modular synthesis of non-peptidic bivalent NPY Y-1 receptor antagonists. BIOORGANIC & MEDICINAL CHEMISTRY, 16 (22). pp. 9858-9866. ISSN 0968-0896,
Full text not available from this repository. (Request a copy)Abstract
According to a 'bivalent ligand approach' to increase the affinity of the potent argininamide-type NPY Y-1 receptor antagonist BIBP-3226, dimeric ligands were synthesized in which two molecules of the parent compound were linked by different spacers via N-G-acylation at the guanidino groups. A synthetic route for the preparation of the title compounds was developed, which includes a copper(I)-catalyzed azide alkyne cycloaddition as the key step. Three bivalent analogues of BIBP-3226 were prepared showing nanomolar antagonistic activity and binding affinity to the NPY Y1 receptor (calcium assay on HEL cells, radioligand binding assay on SK-N-MC cells), but these ligands were not superior to the parent compound and there was no correlation with the length or the chemical nature of the spacer. A trivalent BIBP-3226 derivate showed, surprisingly, no affinity to the NPY Y-1 receptor at all. (C) 2008 Elsevier Ltd. All rights reserved.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | NEUROPEPTIDE-Y; LIGANDS; Neuropeptide Y; Bivalent ligands; Guanidinium compounds; Binding; Huisgen reaction; Cycloaddition |
| Subjects: | 500 Science > 540 Chemistry & allied sciences 600 Technology > 615 Pharmacy |
| Divisions: | Chemistry and Pharmacy > Institute of Pharmacy Chemistry and Pharmacy > Institute of Pharmacy > Alumni or Retired Professors > Pharmaceutical/Medicinal Chemistry II (Prof. Buschauer) Chemistry and Pharmacy > Institut für Organische Chemie Chemistry and Pharmacy > Institut für Organische Chemie > Lehrstuhl Prof. Dr. Burkhard König |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 19 Oct 2020 05:49 |
| Last Modified: | 19 Oct 2020 05:49 |
| URI: | https://pred.uni-regensburg.de/id/eprint/30049 |
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