Synthesis, radiolabeling, and preliminary biological evaluation of [3H]-1-[(S)-N,O-bis-(isoquinolinesulfonyl)-N-methyl-tyrosyl]-4-(o-tolyl)-piperazine, a potent antagonist radioligand for the P2X7 receptor.
The design, synthesis, and preliminary biological evaluation of the first potent radioligand antagonist for the P2X(7) receptor, named [(3)H]-1-[(S)-N,O-bis-(isoquinolinesulfonyl)-N-methyl-tyrosyl]-4-(o-tolyl)-piperazine (compound 13), are reported. This compound bound to human P2X(7) receptors expressed in HEK transfected cells with K(D) and B(max) value of 3.46+/-0.1 nM and 727+/-73 fmol/mg of protein, respectively. The high affinity and facile labeling makes it a promising radioligand for a further characterization of P2X(7) receptor subtype.
Dipartimento di Scienze Farmaceutiche, Università di Ferrara, Via Fossato di Mortara 17/19, 44100 Ferrara, Italy.
Romeo
R
Romagnoli
Pier Giovanni
PG
Baraldi
Maria Giovanna
MG
Pavani
Mojgan Aghazadeh
MA
Tabrizi
Allan R
AR
Moorman
Francesco
F
Di Virgilio
Elena
E
Cattabriga
Cecilia
C
Pancaldi
Stefania
S
Gessi
Pier Andrea
PA
Borea
D001190:Arylsulfonates / Q000138:chemical synthesis* / Q000494:pharmacology*; D001665:Binding Sites; D015195:Drug Design; D005069:Evaluation Studies as Topic; D006801:Humans; D007553:Isotope Labeling / Q000379:methods*; D008024:Ligands; D015394:Molecular Structure; D058919:Purinergic P2 Receptor Antagonists; D058486:Receptors, Purinergic P2X7; D013329:Structure-Activity Relationship; D014316:Tritium / Q000737:chemistry*; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000494:pharmacology*
C473671:1-(N,O-bis(isoquinolinesulfonyl)-N-methyltyrosyl)-4-(4-fluorophenyl)piperazine; D001190:Arylsulfonates; D008024:Ligands; C546468:P2RX7 protein, human; D058919:Purinergic P2 Receptor Antagonists; D058486:Receptors, Purinergic P2X7; D014316:Tritium; D014443:Tyrosine