420137-89-9Relevant academic research and scientific papers
Pyrido[2,1-f]purine-2,4-dione derivatives as a novel class of highly potent human A3 adenosine receptor antagonists
Priego, Eva-María,Von Frijtag Drabbe Kuenzel, Jacobien,IJzerman, Ad P.,Camarasa, María-José,Pérez-Pérez, María-Jesús
, p. 3337 - 3344 (2007/10/03)
1H,3H-Pyrido[2,1-f]purine-2,4-diones, which can be described as fused xanthine structures, have been synthesized by a novel synthetic procedure, and their affinities for the human adenosine A1, A2A, and A3 receptors have been evaluated in radioligand binding studies. The synthetic procedure employed was developed in our laboratory and involved a two-step one-pot reaction that consists of the treatment of 6-aminouracil derivatives with N-bromosuccinimide to generate a 5,5-dibromo-6-imino intermediate that reacts "in situ" with pyridine, 4-methoxypyridine, 4-tert-butylpyridine, or 4-phenylpyridine to afford the corresponding 1H,3H-pyrido-[2,1-f]purine-2,4-diones (2-5). Functionalization at the N3 position in compounds 2-5 was performed by reaction with DBU and different alkyl, alkenyl, alkynyl, or benzyl halides. Binding studies at human adenosine A1, A2A, and A3 receptors revealed significant antagonist effects in the low nanomolar range, in particular against the A3 receptor. Thus, the 1-benzyl-3-propyl-1H,3H-pyrido[2,1-f]purine-2,4-dione derivative 6, which can be considered a lead compound in this series, exhibited a Ki value of 4.0 ± 0.3 nM against the hA3 receptor. Because xanthine derivatives have traditionally been considered poor A3 antagonists, the described pyrido[2,1-f]purine-2,4-dione derivatives represent a new family of adenosine receptor antagonists which deserves further exploration.
A new and efficient one-pot synthesis of pyrido[2,1-f]purine-2,4-diones starting from 6-aminouracil derivatives
Pérez-Pérez,Priego,Jimeno,Camarasa
, p. 155 - 157 (2007/10/03)
A convenient synthesis of pyrido[2,1-f]purine-2,4-diones is described by reaction of 6-aminouracil derivatives with N-bromosuccinimide (NBS) followed by in situ reaction with pyridine or 4-substituted pyridines. A detailed study of the reaction conditions has been performed and a mechanism involving a 5,5-dibromo derivative is proposed.
