. Author manuscript; available in PMC: 2022 Apr 13.

Published in final edited form as: J Med Chem. 2020 Oct 29;63(21):12957–12977. doi: 10.1021/acs.jmedchem.0c01398

Table 2.

SAR on the Triazole Wing: Benzyl Replacements


Compound	R	GLS IC₅₀ (nM)^a	A549 IC₅₀ (nM)^b	Microsomal Stability (mL/min/kg)^c		pH 7.4 Solubility (μM)^d
Compound	R	GLS IC₅₀ (nM)^a	A549 IC₅₀ (nM)^b	Human	Rat	pH 7.4 Solubility (μM)^d
8	Methyl	32	103	0.3	28	0.4
9		100	527	9	64	0.02
10		14	57	35	47	0.15
11		88	471	11	30	37
12		118	789	8	14	0.91
13		23	172	28	50	0.6

Inhibition of purified recombinant human GLS-1 (GAC isoform) assessed via a dual-coupled enzyme assay. IC₅₀ values are reported as the mean of at least three determinations. Standard deviations and counts are included in the supporting information.

Inhibition of proliferation of A549 cells. IC₅₀ values are reported as the mean of at least three determinations. Standard deviations and counts are included in the supporting information.

Liver microsomal intrinsic clearance (mL/min/kg protein).

Kinetic aqueous solubility (μM) in phosphate buffer (100 mM) at pH 7.4; shaken for 1 hour at RT.