Tetrahydro anthranilic acid as a surrogate for anthranilic acid: Application to the discovery of potent niacin receptor agonists

The design, synthesis, and biological activity of a series of cycloalkene acid-based niacin receptor agonists are described. This led to the discovery that tetrahydro anthranilic acid is an excellent surrogate for anthranilic acid. Several compounds were identified that were potent against the niacin receptor, had enhanced cytochrome P450 selectivity against subtypes CYP2C8 and CYP2C9, and improved oral exposure in mice.

Graphical abstractA series of cycloalkene acid-based niacin receptor agonists were designed and synthesized. Several compounds that were potent against the niacin receptor, with enhanced cytochrome P450 selectivity against subtypes CYP2C8and CYP2C9 and had improved oral exposure in mice were identified.Figure optionsDownload full-size imageDownload as PowerPoint slide