| Autor: |
Kelly B; School of Chemistry, Trinity Biomedical Sciences Institute, Trinity College Dublin , 152-160 Pearse Street, Dublin 2, Ireland., McMullan M, Muguruza C, Ortega JE, Meana JJ, Callado LF, Rozas I |
| Jazyk: |
angličtina |
| Zdroj: |
Journal of medicinal chemistry [J Med Chem] 2015 Jan 22; Vol. 58 (2), pp. 963-77. Date of Electronic Publication: 2015 Jan 02. |
| DOI: |
10.1021/jm501635e |
| Abstrakt: |
We have previously identified phenylguanidine and phenyl-2-aminoimidazoline compounds as high affinity ligands with conflicting functional activity at the α2-adrenoceptor, a G-protein-coupled receptor with relevance in several neuropsychiatric conditions. In this paper we describe the design, synthesis, and pharmacological evaluation of a new series of pyridine derivatives [para substituted 2- and 3-guanidino and 2- and 3-(2-aminoimidazolino)pyridines, disubstituted 2-guanidinopyridines and N-substituted-2-amino-1,4-dihydroquinazolines] that were found to be antagonists/inverse agonists of the α2-adrenoceptor. Furthermore, the compounds exert their effects at the α2-adrenoceptor both in vitro in human prefrontal cortex tissue and in vivo in rat brain as shown by microdialysis experiments. We also provide a docking study at the α2A- and α2C-adrenoceptor subtypes demonstrating the structural features required for high affinity binding to the receptor. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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