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. Author manuscript; available in PMC: 2019 Dec 20.
Published in final edited form as: J Med Chem. 2019 Aug 1;62(16):7557–7574. doi: 10.1021/acs.jmedchem.9b00869

Table 4.

Effects of Combined Modifications on Allosteric Activitya

graphic file with name nihms-1062982-t0006.jpg
compd n R4 R5 Log(α) Log(β) −Log(KB) Log(αβ/KB) Δ
1 H H 0.60 ± 0.10 0.36 ± 0.07 4.35 ± 0.12 5.31 ± 0.05 0.00
67 2-F 1.09 ± 0.08 0.09 ± 0.04 4.22 ± 0.10 5.40 ± 0.03 0.09
68 1 4-F 1.01 ± 0.06 0.09 ± 0.03 4.45 ± 0.14 5.55 ± 0.04 0.24
69 3-Me 0.84 ± 0.08 0.14 ± 0.04 4.44 ± 0.12 5.42 ± 0.04 0.11
70 2-OMe 1.12 ± 0.08 −0.12 ± 0.03 4.11 ± 0.04 5.11 ± 0.02 −0.19
71 6-F 4-OPh 0.90 ± 0.06 0.06 ± 0.04 5.85 ± 0.12 6.83 ± 0.08 1.52
72 2 1.06 ± 0.15 0.03 ± 0.07 5.04 ± 0.09 6.13 ± 0.04 0.82
73 3 H 1.19 ± 0.10 0.02 ± 0.03 4.47 ± 0.04 5.67 ± 0.10 0.36
74 4 1.24 ± 0.11 0.06 ± 0.04 4.04 ± 0.11 5.34 ± 0.04 0.03
75 2 4-OPh 1.14 ± 0.09 −0.06 ± 0.03 5.05 ± 0.14 6.14 ± 0.10 0.82
76 3 1.15 ± 0.11 0.01 ± 0.05 4.94 ± 0.11 6.10 ± 0.11 0.81
77 2 1.09 ± 0.10 0.03 ± 0.05 5.14 ± 0.11 6.26 ± 0.09 0.95
78 3 H 1.03 ± 0.07 0.01 ± 0.04 5.35 ± 0.06 6.38 ± 0.05 1.07
79 4 5-CI 1.09 ± 0.13 0.06 ± 0.07 4.98 ± 0.10 6.14 ± 0.10 0.83
80 1 4-OPh 1.05 ± 0.09 0.03 ± 0.03 4.70 ± 0.14 5.78 ± 0.11 0.47
81 2 1.39 ± 0.07 −0.04 ± 0.08 4.59 ± 0.18 5.87 ± 0.14 0.56
a

Values represent means ± SEM from a minimum of three independent assays, each in triplicate or quadruplicate. Δ stands for the difference of Log(αβ/KB) from that of 1; positive values indicate increased allosteric activity, and negative values indicate reduced allosteric activity. Proton concentration-response curves are shown in Supporting Figure 1.