Kagermeier, Nicole and Werner, Kristin and Keller, Max and Baumeister, Paul and Bernhardt, Guenther and Seifert, Roland and Buschauer, Armin (2015) Dimeric carbamoylguanidine-type histamine H-2 receptor ligands: A new class of potent and selective agonists. BIOORGANIC & MEDICINAL CHEMISTRY, 23 (14). pp. 3957-3969. ISSN 0968-0896, 1464-3391
Full text not available from this repository. (Request a copy)Abstract
The bioisosteric replacement of the acylguanidine moieties in dimeric histamine H-2 receptor (H2R) agonists by carbamoylguanidine groups resulted in compounds with retained potencies and intrinsic activities, but considerably improved stability against hydrolytic cleavage. These compounds achieved up to 2500 times the potency of histamine when studied in [S-35]GTP gamma S assays on recombinant human and guinea pig H2R. Unlike 3-(imidazol-4-yl)propyl substituted carbamoylguanidines, the corresponding 2-amino-4-methylthiazoles revealed selectivity over histamine receptor subtypes H1R, H3R and H4R in radioligand competition binding studies. H2R binding studies with three fluorescent compounds and one tritium-labeled ligand, synthesized from a chain-branched precursor, failed due to pronounced cellular accumulation and high non-specific binding. However, the dimeric H2R agonists proved to be useful pharmacological tools for functional studies on native cells, as demonstrated for selected compounds by cAMP accumulation and inhibition of fMLP-stimulated generation of reactive oxygen species in human monocytes. (C) 2015 Elsevier Ltd. All rights reserved.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | G-ACYLATED IMIDAZOLYLPROPYLGUANIDINES; GUANIDINE-TYPE AGONISTS; CHAMELEON LABELS; H-4 RECEPTOR; DIHYDROCHLORIDE; IMMUNOTHERAPY; PROTEINS; REAGENTS; 2ND; Histamine H-2 receptor; Bioisosteric replacement; Bivalent ligand; Receptor subtype selectivity; Human monocytes |
| Subjects: | 500 Science > 540 Chemistry & allied sciences |
| Divisions: | Chemistry and Pharmacy > Institute of Pharmacy > Pharmaceutical/Medicinal Chemistry II (Prof. Buschauer) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 05 Jul 2019 13:19 |
| Last Modified: | 05 Jul 2019 13:19 |
| URI: | https://pred.uni-regensburg.de/id/eprint/5207 |
Actions (login required)
 |
View Item |
