Table 2. Structure–Activity Relationships of 4.
cmpd | X | R1 | R2 | R3 | R4 | ΔTm (°C)a | IC50 (μM)b |
---|---|---|---|---|---|---|---|
4 | S | 4-MeO-Ph | N/A | N/A | N/A | 4.5 ± 1.4 | |
41 | S | H | N/A | N/A | N/A | 1.9 ± 0.7 | |
42 | S | pyrid-3-yl | N/A | N/A | N/A | 2.5 ± 0.4 | |
43 | S | Ph | N/A | N/A | N/A | 7.9 ± 0.5 | ND (>250) |
44 | O | Ph | N/A | N/A | N/A | 8.7 ± 0.5 | 90.8 ± 17.4 |
45 | NH | Ph | N/A | N/A | N/A | 9.2 ± 0.4 | 108.3 ± 16.2 |
46 | S | 4-AcO-Ph | N/A | N/A | N/A | 3.3 ± 0.8 | |
47 | S | 4-CF3-Ph | N/A | N/A | N/A | 2.7 ± 0.8 | |
48 | S | 4-CN-Ph | N/A | N/A | N/A | 2.0 ± 0.8 | |
49 | S | 4-Br-Ph | N/A | N/A | N/A | 4.2 ± 0.7 | |
50 | S | 4-Cl-Ph | N/A | N/A | N/A | 5.1 ± 0.8 | |
51 | S | 4-F-Ph | N/A | N/A | N/A | 3.8 ± 1.7 | |
52 | S | 4-NH2-Ph | N/A | N/A | N/A | 7.1 ± 0.3 | ND (>250) |
53 | S | 4-(HOCH2)-Ph | N/A | N/A | N/A | 4.4 ± 0.6 | |
54 | S | 4-Me-Ph | N/A | N/A | N/A | 5.9 ± 0.7 | 55.0 ± 3.7 |
55 | S | 3-Cl-Ph | N/A | N/A | N/A | 7.3 ± 0.7 | 49.3 ± 17.8 |
56 | S | 3-OH-Ph | N/A | N/A | N/A | 6.1 ± 0.6 | ND (>250) |
57 | S | 3-NH2-Ph | N/A | N/A | N/A | 6.6 ± 0.4 | 235.3 ± 103.4 |
58 | S | 3-MeO-Ph | N/A | N/A | N/A | 7.6 ± 0.7 | ND (>250) |
59 | S | 3-CN-Ph | N/A | N/A | N/A | 3.9 ± 0.6 | |
60 | S | 3-NO2-Ph | N/A | N/A | N/A | 4.9 ± 0.6 | |
61 | S | 2-F-Ph | N/A | N/A | N/A | 5.8 ± 0.7 | 149.1 ± 84.6 |
62 | S | 2-Cl-Ph | N/A | N/A | N/A | 5.0 ± 0.8 | |
63 | S | 2-NH2-Ph | N/A | N/A | N/A | 2.8 ± 0.2 | |
64 | S | 2-NO2-Ph | N/A | N/A | N/A | 4.1 ± 0.5 | |
65 | S | 2-CF3-Ph | N/A | N/A | N/A | 5.3 ± 0.7 | |
66 | N/A | N/A | Br | H | Ph | 7.0 ± 0.8 | 64.8 ± 8.8 |
67 | N/A | N/A | NH2 | H | Ph | 8.5 ± 0.9 | 18.9 ± 3.5 |
68 | N/A | N/A | OMe | H | Ph | 4.4 ± 0.7 | |
69 | N/A | N/A | H | OMe | Ph | 6.4 ± 0.9 | ND (>250) |
70 | N/A | N/A | H | H | 3-MeO-Ph | 7.8 ± 0.7 | 35.5 ± 2.8 |
71 | N/A | N/A | H | H | 4-MeO-Ph | 6.7 ± 0.7 | 89.8 ± 28.6 |
ΔTm values were calculated from DSF experiments by subtracting the Tm of GID4 from the Tm of GID4 in the presence of compound. Each value represents the mean ± SEM of determinations in triplicate.
IC50 values were calculated by averaging displacement curves from FP competition assays. Each value represents the mean ± SEM of determinations in triplicate. ND = not determined.