Table 2.

LDHA Inhibition of 33–63 with comparators 2 and 3^a

Analog	R1	R2	R3	X	LDHA (w/EDTA) IC50 ± SD (μM)
2	NA	NA	NA	NA	0.038 ± 0.004
3	NA	NA	NA	NA	0.424 ± 0.049
33	OH	4-(SO2NH2)-Ph	3,4-F	CH2	0.672 ± 0.077
34	OH	3-(SO2NH2)-Ph	3,4-F	CH2	>57
35	OH	Phenyl	3,4-F	CH2	>57
36	OH	4-(SO2NH2)-Ph	3-Br	CH2	2.37 ± 0.001
37	OH	4-(SO2NH2)-Ph	3-Ph	CH2	0.349 ± 0.023
38	OH	4-(SO2NH2)-Ph	3-(2-F-Ph)	CH2	0.754 ± 0.087
39	OH	4-(SO2NHMe)-Ph	3-Ph	CH2	>57
40	OH	4-(CONH2)-Ph	3-Ph	CH2	>57
41	OH	4-(COOH)-Ph	3-Ph	CH2	33.8 ± 5.5b
42	H	4-(SO2NH2)-Ph	3,4-F	CH2	0.095 ± 0.001
43	H	4-(SO2NH2)-Ph	H	CH2	0.176 ± 0.032
44	H	4-(SO2NH2)-Ph	3-Ph	CH2	0.038 ± 0.001
45	H	4-(SO2NH2)-Ph	H	O	0.124 ± 0.008
46	H	4-(SO2NH2)-Ph	3-Ph	NH	0.057 ± 0.004
47	H	4-(SO2NH2)-Ph	H	NH	0.091 ± 0.006
48	H	4-(SO2NH2)-Ph	H	C(O)NH	>57
49	H		H	CH2	17.3 ± 8.1
50	H		H	CH2	>57
51	Me	4-(SO2NH2)-Ph	H	CH2	0.042 ± 0.001
52	CN	4-(SO2NH2)-Ph	H	CH2	0.115 ± 0.130
53	Ph	4-(SO2NH2)-Ph	H	CH2	0.139 ± 0.009
54	3-pyr	4-(SO2NH2)-Ph	H	CH2	0.349 ± 0.024
55	4-pyr	4-(SO2NH2)-Ph	H	CH2	6.23 ± 0.79
56	NH2	4-(SO2NH2)-Ph	3-Ph	CH2	0.065 ± 0.011
57	CF3	4-(SO2NH2)-Ph	3-Ph	CH2	0.053 ± 0.001
58		4-(SO2NH2)-Ph	H	CH2	0.019 ± 0.001
59		4-(SO2NH2)-Ph	H	O	0.065 ± 0.050
60		4-(SO2NH2)-Ph	3-Ph	O	0.110 ± 0.008
61		4-(SO2NH2)-Ph	3-Ph	CH2	0.027 ± 0.001
62		4-(SO2NH2)-Ph	H	CH2	0.009 ± 0.001
63		4-(SO2NH2)-Ph	3-Ph	CH2	0.032 ± 0.002

^aIC₅₀ 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.

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