Aminoquinazolines as TRPV1 antagonists: Modulation of drug-like properties through the exploration of 2-position substitution

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Abstract

A focused SAR exploration of the lead 4-aminoquinazoline TRPV1 antagonist 2 led to the discovery of compound 18. In rats, compound 18 is readily absorbed following oral dosing and demonstrates excellent in vivo potency and efficacy in an acute inflammatory pain model.

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Acknowledgments

The authors gratefully acknowledge the electrophysiology work of John Dessaint and Gina Borrelli. The authors also thank Lauren Danner (cell culture) and Du-Shieng Chien (pharmacokinetics).

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Present address: Boehringer Ingelheim Pharmaceuticals Inc., Ridgefield, CT, USA.

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