title: Agonists and antagonists acting at P2X7 receptor.
abstract: The P2X(7) receptor is involved in several processes relevant to inflammation (cytokine release, NO generation, killing of intracellular pathogens, cytotoxicity), thus, it may be an appealing target for pharmacological intervention. The characterisation of native and recombinant P2X(7) receptor continues to be hindered by the lack of specific and subtype-selective agonists and antagonists. BzATP is currently the most potent agonist known at the endogenous and recombinant P2X(7) receptor A tyrosine derivative named KN-62 exhibits selective P2X(7) receptor-blocking properties. In this review article we have reported novel series of KN-62-related compounds of the general structure R(1)-Tyr(OR(2))-piperazinyl-R(3), in which three positions (R(1), R(2) and R(3)) were systematically varied. Two recent articles published by AstraZeneca have reported that novel series of cyclic imides and adamantane amides are potent P2X(7) receptor antagonists.
authors.affiliation: Dipartimento di Scienze Farmaceutiche, Universita di Ferrara, Via Fossato di Mortara 17-19, 44100-Ferrara, Italy. pgb@ifeuniv.unife.it
authors.forename: Pier Giovanni
authors.initials: PG
authors.lastname: Baraldi
authors.forename: Francesco
authors.initials: F
authors.lastname: Di Virgilio
authors.forename: Romeo
authors.initials: R
authors.lastname: Romagnoli
mesh_terms: D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D006801:Humans; D058910:Purinergic P2 Receptor Agonists; D058919:Purinergic P2 Receptor Antagonists; D013329:Structure-Activity Relationship
chemical_list: D058910:Purinergic P2 Receptor Agonists; D058919:Purinergic P2 Receptor Antagonists; C033901:3'-O-(4-benzoyl)benzoyladenosine 5'-triphosphate; C063302:KN 62; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D000255:Adenosine Triphosphate