Table 3. SAR on a 7-Membered Ring Scaffold.

compda	R1	R2	EZH2 IC50 (nM)b	Cell IC50 (H3K27me3) (nM)b	Karpas-422 proliferation (nM)b	HLM/MLM (μL/min/mg)	AlogP	MDCK/MDR1 permeability(nm/s) AB, BA/AB
2			1.0	16	122	210/253	3.9	37, 4.8
7	H	Cl	0.35	17	65	79/123	3.0	<1, >51
8	Me	Cl	0.87	208	245	80/112	3.3	<1, >49
9	Et	Cl	33.4				3.7
10	Me	H	2.9		1350	9/–7	2.6	<1, >19
11	Et	H	489				3.0

^aPreparation of compounds 7–11 is summarized in Schemes S7–S11 in the SI.

^bMean of two determinations.