Exploring the Role of N⁶-Substituents in Potent Dual Acting 5'-C-Ethyltetrazolyladenosine Derivatives: Synthesis, Binding, Functional Assays, and Antinociceptive Effects in Mice ∇.

ABSTRACT: Structural determinants of affinity of N⁶-substituted-5'-C-(ethyltetrazol-2-yl)adenosine and 2-chloroadenosine derivatives at adenosine receptor (AR) subtypes were studied with binding and molecular modeling. Small N⁶-cycloalkyl and 3-halobenzyl groups furnished potent dual acting A₁AR agonists and A₃AR antagonists. 4 was the most potent dual acting human (h) A₁AR agonist (K_i = 0.45 nM) and A₃AR antagonist (K_i = 0.31 nM) and highly selective versus A_2A; 11 and 26 were most potent at both h and rat (r) A₃AR. All N⁶-substituted-5'-C-(ethyltetrazol-2-yl)adenosine derivatives proved to be antagonists at hA₃AR but agonists at the rA₃AR. Analgesia of 11,

SUBMITTER: Petrelli R 

PROVIDER: S-EPMC5669264 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature