Table 2.

Results of in silico prediction and in vitro IC₅₀ evaluation of BCRP and P‐gp inhibition for the synthesized compounds (Figure 2).

Compd	log P [a]	Substituents		BCRP		P‐gp
		R1	R2	in silico[b]	IC50 [μm][c]	in silico[b]	IC50 [μm][c]
5 a	2.37	Bn	H	0.25	16.1±3.0	0.97	2.1±0.4
5 b	2.36	Bn	OMe	0.37	3.1±0.5	0.92	2.2±0.6
5 c	0.53	H	H	0.08	n.d.	0.46	58.7±9.2
6 a	1.93	Bn	H	0.39	5.8±1.0	0.98	1.6±0.6
6 b	1.92	Bn	OMe	0.64	3.8±0.6	0.96	11.0±1.0
6 c	0.09	H	H	0.15	n.d.	0.78	n.d.
10 a	2.94	Bn	H	0.17	3.3±0.6	0.88	1.3±0.1
10 b	2.93	Bn	OMe	0.39	2.9±0.5	0.83	1.0±0.2
10 c	1.10	H	H	0.07	n.d.	0.19	34.8±1.8
11 a	2.50	Bn	H	0.40	21.5±2.9	0.94	13.9±1.5
11 b	2.49	Bn	OMe	0.75	2.3±0.0	0.91	6.2±0.4
11 c	0.66	H	H	0.19	n.d.	0.42	n.d.
16 a	2.86	CH3	–	0.22	n.d.	0.97	0.3±0.0
16 b	3.08	CH2F	–	0.19	5.5±0.9	0.97	0.5±0.1
16 c	3.47	CH3F	–	0.24	4.9±1.1	0.97	0.9±0.2

[a] Calculated partition coefficient log P _{octanol/water} determined using Molecular Operating Environment (MOE) version 2014.09. [b] Score between 0 and 1, given by in silico models, roughly corresponds to the probability of being an inhibitor; in silico predictions over 0.5 are marked in bold and represent compounds that are predicted as inhibitors by the models. [c] IC₅₀ values represent the mean±SD of at least n=3 independent experiments performed at least in duplicate; for inhibition of BCRP, 11 a was measured in n=2 independent experiments; the exact number of experiments is given in the Supporting Information (Figure S1 and Table S3); IC₅₀ values were evaluated as described in the Experimental Section; n.d.: not determined.