. Author manuscript; available in PMC: 2024 Jan 27.

Published in final edited form as: J Med Chem. 2023 Apr 7;66(8):5657–5668. doi: 10.1021/acs.jmedchem.2c02089

Table 1:

Selectivity of top 23 compounds inhibiting SNO-CoA-metabolizing activity of SCoR2 versus inhibiting methylglyoxylate-metabolizing activity of AKR1B1.

Number	C2	C3	C4	C7	SCoR2 IC₅₀ (nM)	AKR1B1 IC50 nM	AKR1B1/SCoR
Imirestat (1)	F	H	H	F	57	46	0.81
5-1^* (JSD26)	Cyclopropyl	H	H	H	93	903	9.7
9	Cl	H	H	H	53	16	0.30
16	Cyclopropyl	H	H	F	122	212	1.7
17-1 ^*	Cyclobutyl	H	H	F	33	55	1.7
17-2 ^*	Cyclobutyl	H	H	F	67	44	0.66
20	Cl	H	H	Cl	127	56	0.44
33	F	Cyclopropyl	H	F	72	15	0.21
34	H	OCH₃	H	F	68	16	0.24
38	H	H	F	F	67	16	0.24
45	H	OCH₂CO₂H	H	F	42	53	1.3
46	H	OCH₂CO₂H	H	F	74	13	0.18
47-1 ^*	F	OH	CH₂CO₂H	F	25	42	1.7
47-2 ^*	F	OH	CH₂CO₂H	F	48	32	0.67
48-1 ^*	F	OCH₂CO₂H	H	F	63	27	0.43
48-2 ^*	F	OCH₂CO₂H	H	F	82	22	0.27
49-1 ^*	F	H	CH₂CO₂H	F	57	30	0.53
49-2 ^*	F	H	CH₂CO₂H	F	57	15	0.26
50	F	2-Azetidin-1-yl-2-oxoethoxy	H	F	80	19	0.24
51	F	H	2-(Azetidin-1-yl)-2-oxoethoxy	F	59	18	0.31
52	F	H	1-Cyclopentyl-1H-1,2,3-triazol-4-yl	F	66	11	0.17
53	F	(Oxetan-3-yl)oxy	H	F	29	14	0.48
30	H	H	F	H	82	52	0.63
19	Br	H	H	F	51	22	0.43

individual enantiomers