Abstract:
: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.
journal_name
J Med Chemjournal_title
Journal of medicinal chemistryauthors
Kelly B,McMullan M,Muguruza C,Ortega JE,Meana JJ,Callado LF,Rozas Idoi
10.1021/jm501635esubject
Has Abstractpub_date
2015-01-22 00:00:00pages
963-77issue
2eissn
0022-2623issn
1520-4804journal_volume
58pub_type
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