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. 2022 Sep 19;65(19):12725–12746. doi: 10.1021/acs.jmedchem.2c00509

Table 2. Structure–Activity Relationships of 4.

graphic file with name jm2c00509_0014.jpg

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
a

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.

b

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.