New pyrrolo[2,1-f]purine-2,4-dione and imidazo[2,1-f]purine-2,4-dione derivatives as potent and selective human A3 adenosine receptor antagonists.
Compounds presenting an additional fused ring on the xanthine nucleus have been reported to exhibit antagonistic activity with various levels of affinity and selectivity toward the four adenosine receptors subtypes A(1), A(2A), A(2B), and A(3). This paper reports synthesis and biological evaluation of new 1-benzyl-3-propyl-1H,6H-pyrrolo[2,1-f]purine-2,4-diones and 1-benzyl-3-propyl-1H,8H-imidazo[2,1-f]purine-2,4-diones, among which we identified potent and selective A(3) adenosine receptors antagonists. In particular, 1-benzyl-7-methyl-3-propyl-1H,8H-imidazo[2,1-f]purine-2,4-dione (11e) shows a K(i) (hA(3)) value from binding assay of 0.8 nM.
Baraldi
Pier Giovanni
PG
Dipartimento di Scienze Farmaceutiche, Università di Ferrara, Italy. baraldi@dns.unife.it
Preti
Delia
D
Tabrizi
Mojgan Aghazadeh
MA
Fruttarolo
Francesca
F
Romagnoli
Romeo
R
Zaid
Naser Abdel
NA
Moorman
Allan R
AR
Merighi
Stefania
S
Varani
Katia
K
Borea
Pier Andrea
PA
D058918:Adenosine A3 Receptor Antagonists; D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D000242:Cyclic AMP / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D006801:Humans; D007093:Imidazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011687:Purines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011758:Pyrroles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011869:Radioligand Assay; D013329:Structure-Activity Relationship
C502819:1-benzyl-7-methyl-3-propyl-1H,8H-imidazo(2,1-f)purine-2,4-dione; D058918:Adenosine A3 Receptor Antagonists; D007093:Imidazoles; D011687:Purines; D011758:Pyrroles; D000242:Cyclic AMP