. 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 8.

In vitro drug-like properties of analogs with >10-fold increase in R132C mIDH1 potency over compound 87

		IDH1 R132H	IDH1 R132C	Single Point RLM (t_1/2, min)	PAMPA (10⁻⁶ cm/s)	Solubility (μg/mL)

Compd	R³	IC₅₀ Fold improvement over 87	IC₅₀ Fold improvement over 87
89	nPr	2.8	15	27	134	<1
91	iBu	1.9	13	17	16	<1
92		4.8	26	14	225	<1
93		3.8	31	17	43	<1
98		2.8	12	7	24	<1