title: Carbamate substituted 2-amino-4,6-diphenylpyrimidines as adenosine receptor antagonists.
abstract: 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.
authors.affiliation: Pharmaceutical Chemistry, School of Pharmacy, North-West University, Private Bag X6001, Potchefstroom 2520, South Africa; Centre of Excellence for Pharmaceutical Sciences, North-West University, Private Bag X6001, Potchefstroom 2520, South Africa.
authors.forename: Sarel J
authors.initials: SJ
authors.lastname: Robinson
authors.affiliation: Pharmaceutical Chemistry, School of Pharmacy, North-West University, Private Bag X6001, Potchefstroom 2520, South Africa; Centre of Excellence for Pharmaceutical Sciences, North-West University, Private Bag X6001, Potchefstroom 2520, South Africa.
authors.forename: Jacobus P
authors.initials: JP
authors.lastname: Petzer
authors.affiliation: Molecular Sciences Institute, School of Chemistry, University of the Witwatersrand, Private Bag 3, PO WITS 2050, South Africa.
authors.forename: Amanda L
authors.initials: AL
authors.lastname: Rousseau
authors.affiliation: Pharmaceutical Chemistry, School of Pharmacy, North-West University, Private Bag X6001, Potchefstroom 2520, South Africa; Centre of Excellence for Pharmaceutical Sciences, North-West University, Private Bag X6001, Potchefstroom 2520, South Africa.
authors.forename: Gisella
authors.initials: G
authors.lastname: Terre'Blanche
authors.affiliation: Centre of Excellence for Pharmaceutical Sciences, North-West University, Private Bag X6001, Potchefstroom 2520, South Africa.
authors.forename: Anél
authors.initials: A
authors.lastname: Petzer
authors.affiliation: Pharmaceutical Chemistry, School of Pharmacy, North-West University, Private Bag X6001, Potchefstroom 2520, South Africa; Centre of Excellence for Pharmaceutical Sciences, North-West University, Private Bag X6001, Potchefstroom 2520, South Africa. Electronic address: arina.lourens@nwu.ac.za.
authors.forename: Anna C U
authors.initials: ACU
authors.lastname: Lourens
mesh_terms: D058916:Adenosine A1 Receptor Antagonists / Q000737:chemistry*; D058917:Adenosine A2 Receptor Antagonists / Q000737:chemistry*; D001665:Binding Sites; D002219:Carbamates / Q000737:chemistry; D006801:Humans; D006860:Hydrogen Bonding; D057927:Hydrophobic and Hydrophilic Interactions; D007700:Kinetics; D062105:Molecular Docking Simulation; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011743:Pyrimidines / Q000737:chemistry* / Q000378:metabolism; D043682:Receptor, Adenosine A1 / Q000737:chemistry / Q000378:metabolism; D043705:Receptor, Adenosine A2A / Q000737:chemistry / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D058916:Adenosine A1 Receptor Antagonists; D058917:Adenosine A2 Receptor Antagonists; D002219:Carbamates; D011743:Pyrimidines; D043682:Receptor, Adenosine A1; D043705:Receptor, Adenosine A2A
keywords: 2-Aminopyrimidine; Adenosine A(1) and A(2A) receptor; Antagonist; Dual