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. Author manuscript; available in PMC: 2018 Nov 22.
Published in final edited form as: J Med Chem. 2017 Nov 9;60(22):9184–9204. doi: 10.1021/acs.jmedchem.7b00941

Table 1.

LDHA inhibition of analogs (1, 5–32) with and without EDTAa

graphic file with name nihms928833u2.jpg
Analog R1 R2 LDHA
(w/o EDTA)
IC50 ± SD (μM)		 LDHA (w/EDTA)
IC50 ± SD (μM)
1 NA NA 1.02 ± 0.07 1.34 ± 0.15
5 CF3 Ph 22.2 ± 2.4 b 28.8 ± 1.9
6 Me Ph 15.4 ± 12b >57
7 NH2 Ph 26.7 ± 3 b >57
8 iPr Ph >57 >57
9 CHF2 Ph >57 >57
10 NHAc Ph 9.57 ± 1.8 b >57
11 OH Ph 0.144 ± 0.009 >57
12 CF3 2-Cl-Ph >57 >57
13 CF3 3-Cl-Ph >57 >57
14 CF3 4-Cl-Ph 26.6 ± 0.1 27.7 ± 1.9
15 CF3 4-F-Ph 23.4 ± 5.7 32.3 ± 2.1
16 OH 4-F-Ph 0.095 ± 0.001 >57
17 OH 3-Cl-Ph 0.168 ± 0.001 >57
18 OH 2-F-Ph 0.134 ± 0.001 >57
19 OH 3-F-Ph 0.162 ± 0.011 >57
20 OH 3-CF3-Ph 0.189 ± 0.001 >57
21 OH 3-OCF3-Ph 0.299 ± 0.001 >57
22 OH 4-OMe-Ph 0.229 ± 0.015 >57
23 OH 2-pyridine 1.02 ± 0.07 >57
24 OH 4-pyridine 0.669 ± 0.001 >57
25 OH cyclohexyl 1.10 ± 0.08 >57
26 OH 1-naphthyl 0.213 ± 0.024 >57
27 OH 3,4-F-Ph 0.150 ± 0.001 >57
28 OH 3,4-Cl-Ph 0.106 ± 0.001 >57
29 OH 2,4-F-Ph 0.084 ± 0.001 >57
30 OH 3,5-F-Ph 0.110 ± 0.007 >57
31 OH (3-Ph)-Ph 0.266 ± 0.001 >57
32 OH 3-(2-F-Ph)-Ph 0.095 ± 0.001 >57
a

IC50 values represent the half maximal (50%) inhibitory concentration as determined in the HTS assay (n = 3) using a 22-dose response in 1536-well format.

b

Max. Response was less than 50% and thus IC50 values should be considered as lower confidence.