8-Benzylaminoxanthine scaffold variations for selective ligands acting on adenosine A2A receptors. Design, synthesis and biological evaluation

The Role of (BDMS) Bromodimethylsulfonium bromide as a Catalyst and Brominating Reagent: A Concise Overview

“…An proficient one-pot process was reported by Załuski et al via direct coupling of carboxaldehyde with former accessible 5,6-diaminouracil by the virtue of bromo dimethyl-sulfonium bromide (BDMS) under mild reaction conditions (Scheme 11). [20] Under stoichiometric situation, on coupling of aldehydes with 5, 6-diaminouracil, excellent quantity of xanthines yielded via an imine intermediate or aminal form. The separation of intermediates was fruitless excluding imine form, which was separated at 10 % build-up of bromo dimethylsulfonium bromide (BDMS).…”

Anti-Inflammatory Activities of 8-Benzylaminoxanthines Showing High Adenosine A2A and Dual A1/A2A Receptor Affinity

“…Our previous studies with A 2A R antagonists (xanthine derivatives) showed the anti-inflammatory activity of tested compounds, KD-114 and compound 1 ( Figure 1 ), in carrageenan-induced edema in mice and rats, respectively [ 12 , 13 ]. KD-114 , tested at a dose of 100 mg/kg intraperitoneally ( ip ), significantly (>90%) reduced edema volume in mice at the tested time points (1st, 2nd and 3rd hour).…”

“…An especially strong effect was observed at the first hour with a reduction from 64% (control) to 2% (with the tested compound) [ 12 ]. For compound 1 tested at a dose of 20 mg/kg ip , the strongest inhibition of edema in rats was observed at the 2nd and 3rd hour (44% and 53%, respectively) [ 13 ]. Both compounds display good affinity for the A 2A R (K i = 230 nM, KD-114 ; K i = 69 nM, 1 ) and selectivity towards other adenosine receptors (K i > 1 μM).…”

“… Structures of adenosine A 2A receptor antagonists; h = human; a information from [ 13 ]; b information from [ 9 ]; c information from [ 12 ]. …”

“…Further pharmacological studies, both in vitro and in vivo, were then planned for selected derivatives. Compound 2 ( Figure 1 ) from our previous publication was chosen as a lead structure for the design of new compounds [ 13 ]. This compound was characterized by a high affinity for A 2A R (K i = 71 nM) and the lack of significant interactions with other adenosine receptors (K i > 1000 nM), similar to compound 1 .…”