. 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 1.

Structure-Activity Relationship (SAR) and properties of MI-463 derivatives with various rings introduced at indole nitrogen.


Compound	R	IC₅₀ MLL_4–43 (nM)^a	GI₅₀ (μM)^b MLL-AF9	T_1/2 (min)^c	cLogP^d
1 (MI-463)	H	32 ± 9.9	0.23	14	4.7
2 (MI-503)		33 ± 8.5	0.22	21	4.4
3		15 ± 4.9	0.52	>60	4.3
4		14 ± 1.4	0.81	>60	5.5
5		22 ± 5.7	0.24	<3	4.7
6 (RS)		28 ± 4.9	0.15	31	4.1
7 (RS) (MI-568)		7.5 ± 2.1	0.05	>60	3.7

IC₅₀ values were measured by fluorescence polarization assay using fluorescein labeled MLL_4–43, average values from 2–3 independent measurements ± SD are provided.

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.

Half-life of compounds in mouse liver microsomes.

Calculated with ChemBioDraw Ultra 14.0.