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. Author manuscript; available in PMC: 2020 May 9.
Published in final edited form as: J Med Chem. 2019 Apr 30;62(9):4669–4682. doi: 10.1021/acs.jmedchem.9b00274

Table 3.

TDP2 inhibitory activity and PAMPA permeability for analogues from N-3 modifications (12a-i).

graphic file with name nihms-1024966-t0007.jpg
Compd R′ TDP2 IC50 (μM)a PAMPA Pe (10−6 cm/s)b
4c -- 0.14 ± 0.01 0.008
12a H 0.033 ± 0.001 0.1
12b 4′ Cl 0.033 ± 0.002 0.08
12c 4′ F 0.070 ± 0.003 0.06
12d 4′ Br 0.065 ± 0.003 0.05
12e 3′ CO2Me 0.038 ± 0.003 0.03
12f 3′ CONH2 0.035 ± 0.000 0.01
4b -- 0.042 ± 0.004 0.01
12g 4′ Cl 0.0073 ± 0.0003 0.04
12h 3′ Cl 0.020 ± 0.002 0.07
12i 3′, 4′ di-Cl 0.014 ± 0.000 0.03
a

IC50: concentration of a compound producing 50% inhibition, expressed as mean ± standard deviation from three independent experiments performed in triplicate.

b

Pe: effective permeability coefficients determined using the PAMPA, measured in five replicates.