2. Academic Validation
  3. 2-n-Butyl-9-methyl-8-[1,2,3]triazol-2-yl-9H-purin-6-ylamine and analogues as A2A adenosine receptor antagonists. Design, synthesis, and pharmacological characterization

2-n-Butyl-9-methyl-8-[1,2,3]triazol-2-yl-9H-purin-6-ylamine and analogues as A2A adenosine receptor antagonists. Design, synthesis, and pharmacological characterization

  • J Med Chem. 2005 Nov 3;48(22):6887-96. doi: 10.1021/jm058018d.
Patrizia Minetti 1,  Maria Ornella Tinti,  Paolo Carminati,  Massimo Castorina,  Maria Assunta Di Cesare,  Stefano Di Serio,  Grazia Gallo,  Orlando Ghirardi,  Fabrizio Giorgi,  Luca Giorgi,  Giovanni Piersanti,  Francesca Bartoccini,  Giorgio Tarzia
Affiliations

Affiliation

  • 1 Istituto di Chimica Farmaceutica, Università degli Studi di Urbino Carlo Bo, Piazza del Rinascimento 6, 61029 Urbino (PU), Italy. Patrizia.Minetti@sigma-tau.it
PMID: 16250647 DOI: 10.1021/jm058018d
Abstract

Two types of Adenosine Receptor ligands were designed, i.e., 9H-purine and 1H-imidazo[4,5-c]pyridines, to obtain selective A(2A) antagonists, and we report here their synthesis and binding affinities for the four Adenosine Receptor subtypes A(1), A(2A), A(2B) and A(3). The design was carried out on the basis of the molecular modeling of a number of potent Adenosine Receptor antagonists described in the literature. Three compounds (25b-d) showed an interesting affinity and selectivity for the A(2A) subtype. One of them, i.e., ST1535 (2-n-butyl-9-methyl-8-[1,2,3]triazol-2-yl-9H-purin-6-ylamine, 25b) (K(i) A(2A) = 6.6 nM, K(i) A(1)/A(2A) = 12; K(i) A(2B)/A(2A) = 58; K(i) A(3)/A(2A) > 160), was selected for in vivo study and shown to induce a dose-related increase in locomotor activity, suggestive of an A(2A) antagonist type of activity.

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