Evaluation of adenine as scaffold for the development of novel P2X3 receptor antagonists

Purinergic P2X receptors: Structural models and analysis of ligand-target interaction

“…Considering the inhibitors, different structural classes of compounds have been reported presenting orthosteric or allosteric antagonist profile at the P2X [18], like for example nucleotide derivatives (i.e. 2 0 ,3 0 -O-(2,4,6-trinitrophenyl)-ATP or TNP-ATP [21]; 2 0 ,3 0 -dialdehyde-ATP or oxidized-ATP/oATP, presenting irreversible antagonist activity at the P2X7 receptor), suramin-like analogues, pyrimidine or purine derivatives [22,23], anthraquinones [24]. In the last years, the great interest in particular for the P2X7 subtype as possible therapeutic target has led to the development and publication of a number of antagonists for this receptor [25e38].…”

2′,3′-O-Substituted ATP derivatives as potent antagonists of purinergic P2X3 receptors and potential analgesic agents

“…1), acting as allosteric P2X3 antagonists [51][52][53]. Substitution of the diaminopyrimidine scaffold with a diaminopurine moiety led to compounds that maintained the antagonistic behaviour [54].…”

P2X3 Receptor Ligands: Structural Features and Potential Therapeutic Applications

“…Interestingly, the substituted benzyl moiety of this molecule occupies a sub cavity that is partially occupied also by the trinitrophenyl group of TNP-ATP (Mansoor et al, 2016;Wang et al, 2018). Replacement of the pyrimidine scaffold of these molecules with a purine led to derivatives that, although less potent, retained the ability to block the receptors (Lambertucci et al, 2013). Given the interesting therapeutic potential of molecules that block P2X3 and P2X2/3Rs, in recent years a number of antagonists endowed with a good pharmacokinetic profile and reasonable oral bioavailability have been discovered and reported in numerous patents by pharmaceutical companies (Marucci et al, 2019).…”