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Updated: Aug 15, 2026

Facile Preparation of 4-Substituted Quinazoline Derivatives
Published on: February 15, 2016
Atropisomeric quinazolin-4-one derivatives are potent noncompetitive
W M Welch1, F E Ewing, J Huang
1Global Research and Development, Groton Laboratories, Pfizer Inc., CT 06340, USA.
Abstract:
Piriqualone (1) was found to be an antagonist of AMPA receptors. Structure activity optimization was conducted on each of the three rings in 1 to afford a series of potent and selective antagonists. The sterically crowded environment surrounding the N-3 aryl group provided sufficient thermal stability for atropisomers to be isolated. Separation of these atropisomers resulted in the identification of (+)-38 (CP-465,022), a compound that binds to the AMPA receptor with high affinity (IC50 = 36 nM) and displays potent anticonvulsant activity.
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