| 15771443 |
Vu CB, Pan D, Peng B, Kumaravel G, Smits G, Jin X, Phadke D, Engber T, Huang C, Reilly J, Tam S, Grant D, Hetu G, Petter RC: Novel diamino derivatives of [1,2,4] triazolo [1,5-a][1,3,5] triazine as potent and selective adenosine A2a receptor antagonists. J Med Chem. 2005 Mar 24;48(6):2009-18.
Piperazine derivatives of 2-furanyl [1,2,4] triazolo [1,5-a][1,3,5] triazine have recently been demonstrated to be potent and selective adenosine A (2a) receptor antagonists with oral activity in rodent models of Parkinson's disease. We have replaced the piperazinyl group with a variety of linear, monocyclic, and bicyclic diamines. Of these diamines, (R)-2-(aminomethyl) pyrrolidine is a particularly potent and selective replacement for the piperazinyl group. With this diamine component, we have been able to prepare numerous analogues with low nanomolar affinity toward the A (2a) receptor and good selectivity with respect to the A (1) receptor (> 200-fold in some cases). Selected analogues from this series of [1,2,4] triazolo [1,5-a][1,3,5] triazine have now been shown to be orally active in the mouse catalepsy model. |
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