Choi, Hongseok Jacobson, Kenneth A. Yu, Jinha Jeong, Lak Shin 2024-01-19T15:02:40Z 2024-01-19T15:02:40Z 2022-01-10 2021-04 1424-8247 https://pubs.kist.re.kr/handle/201004/117186 A new series of 4 '-selenoadenosine-5 '-N,N-dimethyluronamide derivatives as highly potent and selective human A(3) adenosine receptor (hA(3)AR) antagonists, is described. The highly selective A(3)AR agonists, 4 '-selenoadenosine-5 '-N-methyluronamides were successfully converted into selective antagonists by adding a second N-methyl group to the 5 '-uronamide position. All the synthesized compounds showed medium to high binding affinity at the hA(3)AR. Among the synthesized compounds, 2-H-N-6-3-iodobenzylamine derivative 9f exhibited the highest binding affinity at hA(3)AR. (K-i = 22.7 nM). The 2-H analogues generally showed better binding affinity than the 2-Cl analogues. The cAMP functional assay with 2-Cl-N-6-3-iodobenzylamine derivative 9l demonstrated hA(3)AR antagonist activity. A molecular modelling study suggests an important role of the hydrogen of 5 '-uronamide as an essential hydrogen bonding donor for hA(3)AR activation. English MDPI Design and Synthesis of 2,6-Disubstituted-4 '-Selenoadenosine-5 '-N,N-Dimethyluronamide Derivatives as Human A(3) Adenosine Receptor Antagonists Article 10.3390/ph14040363 1 PHARMACEUTICALS, v.14, no.4 PHARMACEUTICALS 14 4 N scie scopus 000643403600001 2-s2.0-85119538406 Chemistry, Medicinal Pharmacology & Pharmacy Pharmacology & Pharmacy Article A(3) adenosine receptor structure-activity relationship 4 &apos -Selenonucleosides antagonist