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. Author manuscript; available in PMC: 2021 Sep 10.
Published in final edited form as: J Med Chem. 2020 Aug 13;63(17):9912–9927. doi: 10.1021/acs.jmedchem.0c01017

Table 5.

Inhibition profile against T. brucei and in vitro ADME profile of core modified analogs

graphic file with name nihms-1728327-t0071.jpg
Entry R T. brucei pEC50 a / Log fold Selectivityb T. brucei LLEc Aq. sol. (μM) Human Liver Microsome CLint (uL/min/mg protein) Rat hepatocyte CLint (uL/min/106 cells)
9a graphic file with name nihms-1728327-t0072.jpg 5.1 / >0.80 2.2 60 154 44
9b graphic file with name nihms-1728327-t0073.jpg 5.3 / >1.0 3.8 47 51 8.7
10 graphic file with name nihms-1728327-t0074.jpg 6.4 / 2.1 2.1 12.3 144 56
11 graphic file with name nihms-1728327-t0075.jpg 5.4 / 0.70 1.0 6.9 58 68
13a graphic file with name nihms-1728327-t0076.jpg 5.0 / >0.70 2.0 451 >300 100
13b graphic file with name nihms-1728327-t0077.jpg 4.9 / >0.60 1.6 200 >300 115
a

pEC50=−logEC50

b

Log fold selectivity = T. brucei pEC50-MRC5 pTC50

c

LLE (lipophilic ligand efficiency) = pEC50-clogP

Additional ADME data, including Log D7.4 and human plasma protein binding, are included in Table S1 of the supporting information. All SD within ±0.090