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. Author manuscript; available in PMC: 2020 Feb 19.
Published in final edited form as: J Med Chem. 2018 May 23;61(11):4832–4850. doi: 10.1021/acs.jmedchem.8b00071

Table 3.

SAR and properties of N-substituted analogues of compound 4.

graphic file with name nihms-1011689-t0042.jpg
Compound R IC50 MLL4–43 (nM)a GI50 (μM)b MLL-AF9 T1/2 (min)c cLogPd
4 H 14 ± 1.4 0.81 >60 5.5
24 graphic file with name nihms-1011689-t0033.jpg 63 ± 2.1 0.57 25 4.6
25 graphic file with name nihms-1011689-t0034.jpg 130 ± 32 0.97 26 4.6
26 graphic file with name nihms-1011689-t0035.jpg 40 ± 9.2 0.25 >60 5.2
27 graphic file with name nihms-1011689-t0036.jpg 38 ± 10 0.35 >60 5.6
a

IC50 values were measured by fluorescence polarization assay using fluorescein labeled MLL4–43, average values from 2–3 independent measurements ± SD are provided.

b

Growth inhibition (GI50 values) measured in the MTT cell viability assay after 7 days of treatment of murine bone marrow cells transformed with MLL-AF9.

c

Half-life of compounds in mouse liver microsomes.

d

Calculated with ChemBioDraw Ultra 14.0.