Synthesis and biological evaluation of novel 1-deoxy-1-[6-[((hetero)arylcarbonyl)hydrazino]- 9H-purin-9-yl]-N-ethyl-beta-D-ribofuranuronamide derivatives as useful templates for the development of A2B adenosine receptor agonists.
The lack of molecules endowed with selective and potent agonistic activity toward the hA2B adenosine receptors has limited the studies on this pharmacological target and consequently the evaluation of its therapeutic potential. We report the design and the synthesis of the first potent (EC50 in the nanomolar range) and selective hA2B adenosine receptor agonists consisting of 1-deoxy-1-[6-[((hetero)arylcarbonyl)hydrazino]-9H-purin-9-yl]-N-ethyl-beta-D-ribofuranuronamide derivatives. The concurrent effect of 6-substitution of the purine nucleus with a ((hetero)arylcarbonyl)hydrazino function and a 2-chloro substitution has been investigated in such NECA derivatives.
Baraldi
Pier Giovanni
PG
Dipartimento di Scienze Farmaceutiche, Università di Ferrara, 44100 Ferrara, Italy. baraldi@unife.it
Preti
Delia
D
Tabrizi
Mojgan Aghazadeh
MA
Fruttarolo
Francesca
F
Romagnoli
Romeo
R
Carrion
Maria Dora
MD
Cara
Luisa Carlota Lopez
LC
Moorman
Allan R
AR
Varani
Katia
K
Borea
Pier Andrea
PA
D000241:Adenosine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D058908:Adenosine A2 Receptor Agonists; D000818:Animals; D001667:Binding, Competitive; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D000242:Cyclic AMP / Q000096:biosynthesis; D006801:Humans; D006834:Hydrazines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011869:Radioligand Assay; D013329:Structure-Activity Relationship
D058908:Adenosine A2 Receptor Agonists; D006834:Hydrazines; D000242:Cyclic AMP; D000241:Adenosine