ABSTRACT
The synthesis of new C-6 1,2,3-triazole adenosine derivatives via microwave assisted 1,3-dipolar cycloaddition as key step is described. The binding on membranes of cells that over express A(1) adenosine receptors (A(1)AR) was also evaluated. Among them, four compounds increased cAMP production, in a dose-dependent manner acting as antagonists of the A(1)AR, while two compounds act as agonists.
Subject(s)
Adenosine/chemical synthesis , Purinergic P1 Receptor Agonists/chemical synthesis , Purinergic P1 Receptor Antagonists/chemical synthesis , Receptors, Purinergic P1/metabolism , Triazoles/chemistry , Adenosine/pharmacology , Animals , Cell Line , Cyclic AMP/biosynthesis , Humans , Molecular Structure , Purinergic P1 Receptor Agonists/pharmacology , Purinergic P1 Receptor Antagonists/pharmacologyABSTRACT
The cross talk between different membrane receptors is the source of increasing research. We designed and synthesized a new hetero-bivalent ligand that has antagonist properties on both A(1) adenosine and mu opiate receptors with a K(i) of 0.8+/-0.05 and 0.7+/-0.03 microM, respectively. This hybrid molecule increases cAMP production in cells that over express the mu receptor as well as those over expressing the A(1) adenosine receptor and reverses the antalgic effects of mu and A(1) adenosine receptor agonists in animals.
Subject(s)
Adenosine A1 Receptor Antagonists , Adenosine/analogs & derivatives , Anilides/pharmacology , Drug Design , Receptors, Opioid, mu/antagonists & inhibitors , Adenosine/chemical synthesis , Adenosine/chemistry , Adenosine/pharmacology , Anilides/chemical synthesis , Anilides/chemistry , Ligands , Molecular Structure , Stereoisomerism , Structure-Activity RelationshipABSTRACT
[reaction: see text] The synthesis of the indole skeleton of new melatoninergic analogues was realized using solid-phase methodology in association with microwave irradiation. This combination speeds up the solid-phase drug discovery process in rigorously established conditions.
