Scheme 3. Synthesis and Evaluation of Simplified 6HP-Carboxylic Acid Hybrids 13.

(A) Reagents and conditions: (a) TPAP, NMO, H₂O, MeCN, 23 °C; 1 h; (b) conc. aq. HCl, MeCN, 23 °C, 10 min. 40–85% yield over two steps. (B) Luciferase reporter assay demonstrating ligand efficacy, each bar represents activity at a different concentration of designated compound, from right to left: 0.003, 0.03, 0.3, 1.0, 3.0, 10, and 30 μM. Represented as a measure of fold increase in activity over vehicle. (C) Overlaid dose–response curves of indicated ligands.