Table 1. In Vitro Analysis of SARS-CoV PLpro Inhibition by 15g and Derivatives.
compd | isomera | R1 | R2 | R3 | IC50 (μM)b |
---|---|---|---|---|---|
15g | R | H | H | 3,4-O-CH2-O | 0.67 ± 0.03 |
1a | R,S | Me | H | 3,4-O-CH2-O | 17.2 ± 2.0 |
1b | R,S | OH | H | 3,4-O-CH2-O | 32.0 ± 4.5 |
1c | R,S | OMe | H | 3,4-O-CH2-O | >100 |
1d | R,S | Ph | H | 3,4-O-CH2-O | >100 |
2a | R | H | H | H | 2.2 ± 0.1 |
2b | R | H | (R)-Me | H | 13.5 ± 1.2 |
2c | R | H | (S)-Me | H | 12.7 ± 0.3 |
2d | R | H | (R)-CH2-OMe | H | 18.0 ± 1.9 |
2e | R | H | (S)-CH2-OMe | H | 1.9 ± 0.1 |
3a | R | H | H | 4-Et | 0.47 ± 0.01 |
3b | R | H | H | 4-CO-NH-Me | 0.60 ± 0.02 |
3c | R | H | H | 3-CO-NH-Me | 0.63 ± 0.01 |
3d | R | H | H | 4-NH-CO-Me | 5.7 ± 0.5 |
3e | R | H | H | 3-NH-CO-Me | 0.39 ± 0.01 |
3f | R | H | H | 3-CH2-NH-CO-Me | 20.4 ± 1.2 |
3g | R | H | H | 3-Cl | 27.2 ± 4.1 |
3h | R | H | H | 4-Cl | 0.58 ± 0.02 |
3i | R | H | H | 3,4-diF | 29.2 ± 2.1 |
3j | R | H | H | 4-F | 0.49 ± 0.01 |
3k | R | H | H | 3-F | 0.15 ± 0.01 |
Chiral center.
Values are reported as mean ± standard deviation based on a minimum of triplicate measurements.