Table 4. SAR of Quinazoline-Based Agonists of NTR1, Compounds 37–41.
| compound | R1 | R2 | EC50a (μM) | Emaxa (%) |
|---|---|---|---|---|
| NT(8–13) | 0.001 (>4) | 100.0 | ||
| 5 | 6,7-di-OMe | cyclobutyl | 5.9 ± 0.5 (10) | 85.3 |
| 37 | 6-OMe | cyclobutyl | 10 ± 1.6 | 101.9 |
| 38 | 7-OMe | cyclobutyl | 30 ± 0 (3) | 111.5 |
| 39 | H | cyclobutyl | 23 ± 3.9 | 100.0 |
| 40 | 6,7-OCH2O-dioxolane | cyclobutyl | 34 ± 17 (3) | 87.0 |
| 41 | 6-OMe | cyclopropyl | 4.1 ± 0.5 | 95.7 |
a
HCS NTR1 potency measured relative to the EC100 (100 nM) of the NT(8–13) peptide control average ± SEM (n = 4 unless otherwise noted); Emax was calculated as the % of the response obtained with NT(8–13) peptide. None of the compounds from this series showed activity in the NTR2 (>80 μM) and GPR35 (>40 uM) counterscreens.