2-Aminopyrimidines as dual adenosine A1/A2A antagonists
| Autor: | Gisella Terre’Blanche, Sarel J. Robinson, Anél Petzer, Jacobus P. Petzer, Anna C.U. Lourens, Mietha M. Van der Walt, Jacobus J. Bergh |
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| Přispěvatelé: | 20367414 - Robinson, Sarel Johannes, 10727388 - Petzer, Jacobus Petrus, 10206280 - Terre'Blanche, Gisella, 12264954 - Petzer, Anél, 13035134 - Van der Walt, Mietha Magdalena, 10057072 - Bergh, Jacobus Johannes, 10948724 - Lourens, Anna Catharina U. |
| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
Male
Receptor Adenosine A2A Cell Survival Stereochemistry Parkinson's disease Adenosine A1 Receptor Antagonists Catalepsy Molecular Docking Simulation Rats Sprague-Dawley Structure-Activity Relationship Drug Discovery medicine Animals Humans Structure–activity relationship Binding site Receptor Cytotoxicity Cells Cultured Pharmacology Dose-Response Relationship Drug Molecular Structure Receptor Adenosine A1 Chemistry Organic Chemistry General Medicine medicine.disease Adenosine Affinities Adenosine A1 antagonist Adenosine A2 Receptor Antagonists Rats Pyrimidines Adenosine A2A antagonist 2-Aminopyrimidine Haloperidol HeLa Cells medicine.drug |
| Popis: | In this study thirteen 2-aminopyrimidine derivatives were synthesised and screened as potential antagonists of adenosine A1 and A2A receptors in order to further investigate the structure activity relationships of this class of compounds. 4-(5-Methylfuran-2-yl)-6-[3-(piperidine-1-carbonyl)phenyl]pyrimidin-2-amine (8m) was identified as a compound with high affinities for both receptors, with an A2AKi value of 6.34 nM and an A1Ki value of 9.54 nM. The effect of selected compounds on the viability of cultured cells was assessed and preliminary results indicate low cytotoxicity. In vivo efficacy at A2A receptors was illustrated for compounds 8k and 8m since these compounds attenuated haloperidol-induced catalepsy in rats. A molecular docking study revealed that the interactions between the synthesised compounds and the adenosine A2A binding site most likely involve Phe168 and Asn253, interactions which are similar for structurally related adenosine A2A receptor antagonists North-West University, Medical Research Council (MRC) and the National Research Foundation (UID 76308) |
| Databáze: | OpenAIRE |
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