646512-01-8Relevant academic research and scientific papers
New strategies for the synthesis of A3 adenosine receptor antagonists
Baraldi, Pier Giovanni,Bovero, Andrea,Fruttarolo, Francesca,Romagnoli, Romeo,Tabrizi, Mojgan Aghazadeh,Preti, Delia,Varani, Katia,Borea, Pier Andrea,Moorman, Allan R.
, p. 4161 - 4169 (2007/10/03)
New A3 adenosine receptor antagonists were synthesized and tested at human adenosine receptor subtypes. An advanced synthetic strategy permitted us to obtain a large amount of the key intermediate 5 that was then submitted to alkylation procedures in order to obtain the derivatives 6-8. These compounds were then functionalised into ureas at the 5-position (compounds 9-11, 18 and 19) to evaluate their affinity and selectivity versus hA3 adenosine receptor subtype; in particular, compounds 18 and 19 displayed a value of affinity of 4.9 and 1.3 nM, respectively. Starting from 5, the synthetic methodologies employed permitted us to perform a rapid and a convenient divergent synthesis. A further improvement allowed the regioselective preparation of the N8-substituted compound 7. This method could be used as an helpful general procedure for the design of novel A3 adenosine receptor antagonists without the difficulty of separating the N8-substituted pyrazolo[4,3-e]1,2,4-triazolo[1,5-c]pyrimidines from the corresponding N 7-isomers.
