Abstract
P2X purinoceptors are ligand-gated ion channels whose endogenous ligand is ATP. Both the P2X(3) and P2X(2/3) receptor subtypes have been shown to play an important role in the regulation of sensory function and dual P2X(3)/P2X(2/3) antagonists offer significant potential for the treatment of pain. A high-throughput screen of the Roche compound collection resulted in the identification of a novel series of diaminopyrimidines; subsequent optimization resulted in the discovery of RO-4, a potent, selective and drug-like dual P2X(3)/P2X(2/3) antagonist.
MeSH terms
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Adenosine Triphosphate / chemistry
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Analgesics / chemical synthesis*
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Analgesics / pharmacology*
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Chemistry, Pharmaceutical / methods*
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Drug Design
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Drug Evaluation, Preclinical
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Humans
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Inhibitory Concentration 50
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Ions
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Ligands
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Models, Chemical
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Pain / drug therapy*
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Purinergic P2 Receptor Antagonists*
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Pyrimidines / chemical synthesis*
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Pyrimidines / pharmacology*
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Receptors, Purinergic P2 / chemistry
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Structure-Activity Relationship
Substances
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Analgesics
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Ions
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Ligands
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Purinergic P2 Receptor Antagonists
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Pyrimidines
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RO-4 compound
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Receptors, Purinergic P2
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Adenosine Triphosphate