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. Author manuscript; available in PMC: 2018 Jun 23.
Published in final edited form as: J Med Chem. 2017 Jul 13;60(14):6364–6383. doi: 10.1021/acs.jmedchem.7b00561

Table 3.

Effect of Core Scaffold Modifications on Potency, Cytotoxicity, and in Vitro Biopharmaceutical Properties

entry/cmpd structure cell-based activity and cytotoxicity in vitro pharmacokinetic assays
potency, EC50 (μM)a cytotoxicity, CC50 (μM)a selectivity index (CC50/EC50) rat liver microsome stability t1/2 (min) PAMPA permeability (1×10−6 cm/s) aqueous solubility (μg/ml)
13 graphic file with name nihms972420t56.jpg 0.081 ± 0.041 7.053 ± 0.788 87 7.4 NDb >71
18a graphic file with name nihms972420t57.jpg 0.038 ± 0.037 12.967 ± 0.851 341 14.1 215.4 >70
18b graphic file with name nihms972420t58.jpg 0.055 ± 0.020 6.195 ± 0.587 113 2.5 276.4 >72
a

Average of three separate assays (unless otherwise noted) ± standard deviation.

b

ND, not determined.