# 2-Aryladenine Derivatives as a Potent Scaffold for Adenosine Receptor Antagonists: The 6-Morpholino Derivatives

## TL;DR

This study explores new 2-aryladenine compounds that act as strong blockers of adenosine receptors, which could lead to new drugs or research tools.

## Contribution

The paper introduces new 2-aryladenine derivatives with potent and selective adenosine receptor antagonism.

## Key findings

- Eleven compounds showed potent antagonism at various adenosine receptor subtypes.
- Three compounds had high affinity but no selectivity for specific receptors.
- Structure-activity relationships revealed potency and selectivity differences between 9-methyl and 9H-purine derivatives.

## Abstract

A set of 2-aryl-9-H or methyl-6-morpholinopurine derivatives were synthesized and assayed through radioligand binding tests at human A1, A2A, A2B, and A3 adenosine receptor subtypes. Eleven purines showed potent antagonism at A1, A3, dual A1/A2A, A1/A2B, or A1/A3 adenosine receptors. Additionally, three compounds showed high affinity without selectivity for any specific adenosine receptor. The structure-activity relationships were made for this group of new compounds. The 9-methylpurine derivatives were generally less potent but more selective, and the 9H-purine derivatives were more potent but less selective. These compounds can be an important source of new biochemical tools and/or pharmacological drugs.