Table 1.

Structures and c-Met Inhibitory Potencies of Compounds 5a–5h with Calculated ΔΔG_cal Values Compared with 5a

Compound	Block A	R1	c-Met (IC50, nM)		ΔΔGcal (kcal mol−1)
			Enzyme-Baseda	Cell-Basedb
5a		4-OMe	9,279	-c	0
5b		4-OMe	1,000	-c	−1.31
5c		4-OMe	602.5	-c	−1.45
5d		4-CF3	40.3	24,987	−3.12
5e		2-F	28.8	194.2	−3.12
5f		3-F	67.6	600.8	−2.95
5g		4-F	9.7	47.3	−3.15
5h		-H	69.7	358.4	−3.03

^aIn vitro kinase assays were performed with the indicated purified recombinant c-Met kinase domains (nM).

^bIC₅₀ values (nM) for HGF-mediated autophosphoylation in MKN-45 cells.

^cNot tested.