A pyridoxine cyclic phosphate and its 6-azoaryl derivative selectively potentiate and antagonize activation of P2X1 receptors.
KA Jacobson, YC Kim, SS Wildman, A Mohanram, TK Harden, JL Boyer, BF King, G Burnstock
Journal of Medicinal Chemistry | Published : 1998
Analogues of the P2 receptor antagonists pyridoxal-5'-phosphate and the 6-azophenyl-2',4'-disulfonate derivative (PPADS), in which the phosphate group was cyclized by esterification to a CH2OH group at the 4-position, were synthesized. The cyclic pyridoxine-alpha4, 5-monophosphate, compound 2 (MRS 2219), was found to be a selective potentiator of ATP-evoked responses at rat P2X1 receptors with an EC50 value of 5.9 +/- 1.8 microM, while the corresponding 6-azophenyl-2',5'-disulfonate derivative, compound 3 (MRS 2220), was a selective antagonist. The potency of compound 3 at the recombinant P2X1 receptor (IC50 10.2 +/- 2.6 microM) was lower than PPADS (IC50 98.5 +/- 5.5 nM) or iso-PPADS (IC50 ..View full abstract
Awarded by NIGMS NIH HHS
Awarded by NHLBI NIH HHS