. Author manuscript; available in PMC: 2022 Mar 31.

Published in final edited form as: J Med Chem. 2021 Apr 6;64(8):4913–4946. doi: 10.1021/acs.jmedchem.1c00019

Table 5.

Ring-opened core modifications.



Biochemical	IDH1 R132H		IDH1 R132C

Core	IC₅₀(μM) ± SD^a	% inhibition ± SD at 38 μM	IC₅₀(μM) ± SD^a	% inhibition ±SD at 38 μM
1	1.6 ± 0.2	84 ± 7	1.0 ± 0.3	85 ± 4
10	2.3 ± 0.0	84 ± 1		65 ± 4
66	0.69 ± 0.05	89 ± 2	0.24 ± 0.05	82 ± 4
67	> 38	-	> 38	-
68	7.2 ± 0.5	102 ± 1		72 ± 3
69	> 38	-	> 38	-
70	1.5 ± 0.0	87 ± 3		64 ± 5

IC₅₀ values were determined utilizing the diaphorase and resazurin-coupled R132H and R132C mIDH1 assays. IC₅₀ is reported only for compounds with >75% inhibition at 38μM, the highest concentration tested.