2-Aryladenine derivatives as a potent scaffold for A(1), A(3) and dual A(1)/A(3) adenosine receptor antagonists: Synthesis and structure-activity relationships

• Published in: Bioorganic & medicinal chemistry Vol. 27; no. 16; pp. 3551 - 3558
• Main Authors: Areias, Filipe, Correia, Carla, Rocha, Ashly, Brea, Jose, Castro, Marian, Loza, Maria, Fernanda Proenca, M., Alice Carvalho, M.
• Format: Journal Article
• Language: English
• Published: OXFORD Elsevier 15.08.2019
• Subjects: Biochemistry & Molecular Biology; Chemistry; Chemistry, Medicinal; Chemistry, Organic; Life Sciences & Biomedicine; Pharmacology & Pharmacy; Physical Sciences; Science & Technology; Adenine derivatives; MEDICINAL CHEMISTRY; Adenosine receptor antagonists; LIGANDS; 2-Arylpurine derivatives
• ISSN: 0968-0896; 1464-3391
• DOI: 10.1016/j.bmc.2019.06.034

From a collection containing more than 1500 academic compounds, in silico screening identified a hit for the human A(1) adenosine receptor containing a new purine scaffold. To study the structure activity relationships of this new chemical series for adenosine receptors, a library of 24 purines was synthesized and tested in radioligand binding assays at human A(1), A(2A), A(2B) and A(3) adenosine receptor subtypes. Fourteen molecules showed potent antagonism at A(1), A(3) or dual A(1)/A(3) adenosine receptors. This purine scaffold is an important source for novel biochemical tools and/or therapeutic drugs.