Aiglstorfer, Iris and Uffrecht, Anka and Gessele, Karin and Moser, Christiane and Schuster, Andreas and Merz, Stefanie and Malawska, Barbara and Bernhardt, Günther and Dove, Stefan and Buschauer, Armin (1998) NPY Y-1 antagonists: structure-activity relationships of arginine derivatives and hybrid compounds with arpromidine-like partial structures. REGULATORY PEPTIDES, 75-76. pp. 9-21. ISSN 0167-0115, 1873-1686
Full text not available from this repository. (Request a copy)Abstract
Previously, omega-guanidino- and omega-aminoalkanamides, structurally derived from arpromidine-like histamine H-2 receptor agonists, were reported as novel neuropeptide Y Y-1 antagonists. Regardless of the backbone, they resemble BIBP 3226, an argininamide with high NPY Y-1 receptor affinity and selectivity, with respect to nature and arrangement of the 'terminal' diaryl, guanidine, and hydroxyphenyl groups. Hybrid compounds were synthesized combining the argininamide backbone of BIBP 3226 or partial structures derived from the C-terminal dipeptide of NPY with characteristic substructures of arpromidine- or amide-type NPY antagonists. Additionally, some analogs of BIBP 3226 with reduced flexibility were prepared. Structure-activity relationships indicate that, in contrast to alkanamides, homologs and/or isomers of BIBP 3226 with vicinal arrangement of the phenyl rings have decreased Y-1 antagonistic activity (Ca2+-assay in HEL cells). Replacement of the hydroxybenzyl group by an imidazole ring further decreases activity. It is concluded that the binding sites of NPY antagonists with one and with two basic groups are not identical. Analogs with a rigid tetrahydro-2-benzazepine or an indan group in place of the benzyl moiety in BIBP 3226 are active, indicating the role of the OH group and supporting the model proposed for the interaction of BIBP 3226 with the Y-1 receptor. (C) 1998 Elsevier Science BN. All rights reserved.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | NEUROPEPTIDE-Y; PEPTIDE-SYNTHESIS; RECEPTORS; BINDING; neuropeptide Y; NPY antagonists; calcium assay; radioligand binding |
| Subjects: | 500 Science > 540 Chemistry & allied sciences 600 Technology > 615 Pharmacy |
| Divisions: | Chemistry and Pharmacy > Institute of Pharmacy > Pharmaceutical/Medicinal Chemistry II (Prof. Buschauer) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 16 Feb 2023 07:29 |
| Last Modified: | 16 Feb 2023 07:29 |
| URI: | https://pred.uni-regensburg.de/id/eprint/49487 |
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