Carbamate substituted 2-amino-4,6-diphenylpyrimidines as adenosine receptor antagonists

Autor: Sarel J. Robinson, Jacobus P. Petzer, Amanda L. Rousseau, Gisella Terre’Blanche, Anél Petzer, Anna C.U. Lourens
Přispěvatelé: 10948724 - Lourens, Anna Catharina U., 12264954 - Petzer, Anél, 10727388 - Petzer, Jacobus Petrus, 20367414 - Robinson, Sarel Johannes, 10206280 - Terre'Blanche, Gisella
Rok vydání: 2015
Předmět:
0301 basic medicine
Carbamate
Receptor
Adenosine A2A
Stereochemistry
medicine.medical_treatment
Clinical Biochemistry
Pharmaceutical Science
Adenosine A1 Receptor Antagonists
Biochemistry
03 medical and health sciences
Structure-Activity Relationship
0302 clinical medicine
In vivo
Drug Discovery
medicine
Dual
Structure–activity relationship
Humans
Binding site
Receptor
Molecular Biology
Binding Sites
Chemistry
Receptor
Adenosine A1
Organic Chemistry
Antagonist
Hydrogen Bonding
Adenosine
Adenosine receptor
Adenosine A2 Receptor Antagonists
Protein Structure
Tertiary
Molecular Docking Simulation
Kinetics
030104 developmental biology
Pyrimidines
2-Aminopyrimidine
Adenosine A1 and A2A receptor
Molecular Medicine
Carbamates
Hydrophobic and Hydrophilic Interactions
030217 neurology & neurosurgery
medicine.drug
Protein Binding
Zdroj: Bioorganicmedicinal chemistry letters. 26(3)
ISSN: 1464-3405
Popis: A novel series of carbamate substituted 2-amino-4,6-diphenylpyrimidines was evaluated as potential dual adenosine A1 and A2A receptor antagonists. The majority of the synthesised compounds exhibited promising dual affinities, with A1Ki values ranging from 0.175 to 10.7 nM and A2AKi values ranging from 1.58 to 451 nM. The in vivo activity illustrated for 3-(2-amino-6-phenylpyrimidin-4-yl)phenyl morpholine-4-carboxylate (4c) is indicative of the potential of these compounds as therapeutic agents in the treatment of Parkinson's disease, although physicochemical properties may require optimisation.
Databáze: OpenAIRE
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