Substituted conformationally restricted guanidine derivatives: Probing the α2-adrenoceptors’ binding pocket
| Autor: | Isabel Rozas, Patricia Miranda-Azpiazu, Aintzane García-Bea, Michela McMullan, Luis F. Callado |
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| Rok vydání: | 2016 |
| Předmět: |
Stereochemistry
Binding pocket Ligands 010402 general chemistry 01 natural sciences Structure-Activity Relationship α2 adrenoceptor Receptors Adrenergic alpha-2 Drug Discovery Humans Molecule Guanidine Guanidine derivatives Biological evaluation Pharmacology Binding Sites biology 010405 organic chemistry Chemistry Organic Chemistry Brain Active site General Medicine Adrenergic alpha-2 Receptor Antagonists Combinatorial chemistry 0104 chemical sciences Molecular Docking Simulation Ring size Drug Design biology.protein Protein Binding |
| Zdroj: | European Journal of Medicinal Chemistry. 123:48-57 |
| ISSN: | 0223-5234 |
| DOI: | 10.1016/j.ejmech.2016.07.011 |
| Popis: | In this paper we report the design, synthesis and pharmacological evaluation of new N-substituted 2-amino-1,4-dihydroquinazolines, 2-amino-1,4-dihydropyridopyrimidines and 2-amino-4,5-dihydro-1,3-benzodiazepines as α2-adrenoceptors ligands. Computational studies show that the proposed substitutions and guanidine-containing ring size will probe an extensive area of the active site. Preparation of these molecules involved novel routes than those previously utilised in our laboratory for the preparation of the acyclic aryl-guanidine counterparts. Compounds 8b and 18c showed the highest affinity and antagonistic activity, within their series, towards the α2-adrenoceptor in human brain tissue in vitro experiments. Structure-activity relationships have been established for the design and biological evaluation of novel α2-adrenoceptor ligands. |
| Databáze: | OpenAIRE |
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