Numerous potent P2X3 antagonists have been discovered and the therapeutic potential of P2X3 antagonism already comprises proof-of-concept data obtained in clinical trials with the most advanced compound. We have lately reported the discovery and optimization of thia-triaza-tricycle compounds with potent P2X3 antagonistic properties. This Letter describes the SAR of a back-up series containing a 4-oxo-quinazoline central ring. The discovery of the highly potent compounds 51 is presented.
Keywords: 4-Oxo-6-aryl-phenethyl-quinazolines; ATP; Chronic cough; Ion channel; Nanomolar activity; P2X3 antagonist; Purinergic receptor; Structure–activity relationship.
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