New A3 adenosine receptor antagonists I [R1 = HO(CH2)2, (EtO)2CHCH2, HO2CCH2, etc.; R2 = H, PhNHCO, 3-ClC6H4NHCO] were synthesized and tested at human adenosine receptor subtypes. An advanced synthetic strategy permitted us to obtain a large amt. of the key intermediate I (R1 = R2 = H) that was then submitted to alkylation procedures in order to obtain I [R1 = HO(CH2)2, (EtO)2CHCH2, Me3CO2CCH2, etc.; R2 = H]. The latter were then functionalized into ureas at the 5-position to evaluate their affinity and selectivity vs. hA3 adenosine receptor subtype; in particular, I [R1 = PhCH2O(CH2)2, HO(CH2)2; R2 = PhNHCO] displayed a value of affinity of 4.9 and 1.3 nM, resp. Starting from I (R1 = R2 = H), the synthetic methodologies employed allowed to perform a rapid and a convenient divergent synthesis. This method could be used as a general procedure for the design of novel A3 adenosine receptor antagonists without the difficulty of sepg. the N8-substituted pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidines from the corresponding N7-isomers.

New strategies for the synthesis of A(3) adenosine receptor antagonists

BARALDI, Pier Giovanni;BOVERO, Andrea;FRUTTAROLO, Francesca;ROMAGNOLI, Romeo;AGHAZADEH TABRIZI, Mojgan;PRETI, Delia;VARANI, Katia;BOREA, Pier Andrea;
2003

Abstract

New A3 adenosine receptor antagonists I [R1 = HO(CH2)2, (EtO)2CHCH2, HO2CCH2, etc.; R2 = H, PhNHCO, 3-ClC6H4NHCO] were synthesized and tested at human adenosine receptor subtypes. An advanced synthetic strategy permitted us to obtain a large amt. of the key intermediate I (R1 = R2 = H) that was then submitted to alkylation procedures in order to obtain I [R1 = HO(CH2)2, (EtO)2CHCH2, Me3CO2CCH2, etc.; R2 = H]. The latter were then functionalized into ureas at the 5-position to evaluate their affinity and selectivity vs. hA3 adenosine receptor subtype; in particular, I [R1 = PhCH2O(CH2)2, HO(CH2)2; R2 = PhNHCO] displayed a value of affinity of 4.9 and 1.3 nM, resp. Starting from I (R1 = R2 = H), the synthetic methodologies employed allowed to perform a rapid and a convenient divergent synthesis. This method could be used as a general procedure for the design of novel A3 adenosine receptor antagonists without the difficulty of sepg. the N8-substituted pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidines from the corresponding N7-isomers.
2003
Baraldi, Pier Giovanni; Bovero, Andrea; Fruttarolo, Francesca; Romagnoli, Romeo; AGHAZADEH TABRIZI, Mojgan; Preti, Delia; Varani, Katia; Borea, Pier A...espandi
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11392/516864
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