A2B receptor ligands: past, present and future trends

Area of Science:

• Pharmacology
• Medicinal Chemistry

Background:

• Adenosine A(2B) receptors are implicated in diverse physiological processes, including inflammation, glucose regulation, and cardioprotection.
• Targeting A(2B) receptors offers therapeutic potential for various pathologies.
• Development of selective ligands has been historically challenging due to a lack of potent compounds.

Purpose of the Study:

• To review recent advancements in the synthesis and structure-activity relationships of A(2B) adenosine receptor ligands.
• To highlight promising A(2B) antagonists and agonists for therapeutic development.

Main Methods:

• Literature review of recent synthetic efforts and biological evaluations of A(2B) receptor ligands.
• Analysis of structure-activity relationships for identified compounds.
• Summary of preclinical findings for selected antagonists and agonists.

Main Results:

• Significant progress has been made in developing potent and selective A(2B) antagonists, particularly xanthine-based compounds like CVT-6883, MRE-2029-F20, LAS38096, OSIP339391, PSB601, and deazaxanthine 32.
• These antagonists exhibit high affinity (nM range) and selectivity over other adenosine receptor subtypes.
• The development of A(2B) agonists is less advanced, with compound 65 and BAY-60-6583 being notable examples under preclinical investigation.

Conclusions:

• Selective A(2B) antagonists, especially xanthine derivatives, are progressing towards clinical applications.
• Further research into A(2B) agonists is needed, particularly for their potential role in ischemic preconditioning.
• The development of novel A(2B) ligands holds promise for treating a range of diseases.