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. 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 1.

Core modifications and SAR.

graphic file with name nihms-1769820-t0038.jpg
Biochemical IDH1 R132H IDH1 R132C
Compound IC50(μM) ± SDa % inhibition ± SD at 38 μM IC50(μM) ± SDa % inhibition ± SD at 38 μM
1 1.6 ± 0.2 84 ± 7 1.0 ± 0.3 85 ± 9
2 > 38 - > 38 -
3 > 38 - > 38 -
4 3.6 ± 0.5 87 ± 3 - 64 ± 5
5 3.0 ± 0.3 96 ± 4 1.7 ± 0.2 76 ± 2
6 - 62 ± 1 - 43 ± 1
7 - 38 ± 1 - 29 ± 4
8 - 35 ± 0 - 36 ± 2
9 8.0 ± 2.4 75 ± 15 - 32 ± 3
10 2.3 ± 0.0 84 ± 1 - 65 ± 4
a

IC50 values were determined utilizing the diaphorase and resazurin-coupled R132H and R132C mIDH1 assays (average of N = 3). IC50 values are reported only for compounds where ≥75% inhibition of enzyme activity was observed at the highest concentration tested (38 μM).