Synthesis of adenosine A2 receptor antagonists as potential anti-Parkinson drugs (completed)

About the project

Adenosine is a signaling substance, which mediate its effects by activation of fours different G-protein-coupled receptors (GPCR) (A1, A2A, A2B and A3). The ARs differs in their affinity for adenosine as well as their downstream signaling pathways activated in the target cells. The ARs are present in basically every cell in the body, but their abundance in different tissue.

Caffeine is a classical non-selective AR antagonist with high affinities for A1 and A2A and low affinities for A2B and A3 receptors. The excitatory effects of caffeine are a result of its ability to antagonize adenosine activity at A1 receptors in the central nervous system. The main objectives of this project are to develop selective antagonists for the various sub-types of ARs which may lead to drug candidates and/or molecular tools, and to increased knowledge of structure – activity relationships (SAR) and binding modes for AR ligands. A selective ligand for one of the ARs may have a drug potential, i.e. A2A antagonists as anti-Parkinson drugs. Antagonists for the other receptors may have other potential applications, not limited to CNS activity; A1 antagonists for treatment of asthma, A2A antagonists as anti-Parkinson drugs, A2B antagonists for treatment of chronic pulmonary diseases and A3 antagonists as anti-cancer agents.

Financing

The project was financed by NFR – KOSK II (2009-2011).

Cooperation

External collaborator: Prof. Christa Müller, Bonn University.

Participants

 Placid Orji (Ms student), Aisvareia Kulendrn (Ms student).

Published Dec. 21, 2010 10:31 AM - Last modified Mar. 30, 2015 2:17 PM

Contact