Design, synthesis, and biological evaluation of LNA nucleosides as adenosine A3 receptor ligands

Bioorganic & Medicinal Chemistry
2007.0

Abstract

We have prepared a series of adenosine analogs based on the bicyclo[2.2.1]heptane scaffold of locked nucleic acid (LNA) and tested them for both agonist and antagonist activity at the adenosine A(3) receptor. The design of these derivatives was based on the known A(3) agonist IB-MECA and related compounds. Modifications thus include the 5'-uronamides and N(6)-(3-iodobenzyl) derivatives. In this way we have prepared analogs of known A(3) agonists with the sugar ring restricted in an N-conformation. For comparison we have also prepared 2'-O-methyl derivatives of IB-MECA. The LNA nucleosides showed no agonist activity but some of them are potent antagonists. The 2'-O-methyl derivative of IB-MECA is an agonist with similar potency as the parent compound.

Knowledge Graph

Similar Paper

Design, synthesis, and biological evaluation of LNA nucleosides as adenosine A3 receptor ligands
Bioorganic & Medicinal Chemistry 2007.0
Structural Determinants of A<sub>3</sub> Adenosine Receptor Activation:  Nucleoside Ligands at the Agonist/Antagonist Boundary
Journal of Medicinal Chemistry 2002.0
Methanocarba Analogues of Purine Nucleosides as Potent and Selective Adenosine Receptor Agonists
Journal of Medicinal Chemistry 2000.0
2‘-C-Methyl Analogues of Selective Adenosine Receptor Agonists:  Synthesis and Binding Studies
Journal of Medicinal Chemistry 1998.0
Design, Synthesis, and Biological Activity of <scp>l</scp>-1′-Homologated Adenosine Derivatives
ACS Medicinal Chemistry Letters 2022.0
Polypharmacology ofN<sup>6</sup>-(3-Iodobenzyl)adenosine-5′-N-methyluronamide (IB-MECA) and Related A<sub>3</sub>Adenosine Receptor Ligands: Peroxisome Proliferator Activated Receptor (PPAR) γ Partial Agonist and PPARδ Antagonist Activity Suggests Their Antidiabetic Potential
Journal of Medicinal Chemistry 2017.0
N<sup>6</sup>,5‘-Disubstituted Adenosine Derivatives as Partial Agonists for the Human Adenosine A<sub>3</sub> Receptor
Journal of Medicinal Chemistry 1999.0
Adenosine receptor agonists: synthesis and biological evaluation of 1-deaza analogs of adenosine derivatives
Journal of Medicinal Chemistry 1988.0
2-Substitution of N6-Benzyladenosine-5'-uronamides Enhances Selectivity for A3 Adenosine Receptors
Journal of Medicinal Chemistry 1994.0
Synthesis and evaluation of adenosine derivatives as A1, A2A, A2B and A3 adenosine receptor ligands containing boron clusters as phenyl isosteres and selective A3 agonists
European Journal of Medicinal Chemistry 2021.0