Table 1.

Inhibition of in vitro ubiquitination of p53 by HDM2 by substituted 10-aryl (I) and 10-alkyldeazaflavins (II)^a

Compd										Prescreen	IC50 (μM)
	R1	R2	R3	R4	R5	R6	R7	R8	R9
5 (I)	H	H	H	NO2	F	H	H	H	—	Active	>100
6 (I)	H	NO2	H	H	H	H	Cl	H	—	Active	>75
7 (I)	H	H	H	NO2	H	H	Cl	H	—	Active	>50
8 (I)	H	H	H	CF3	H	H	H	H	—	Active	17.5b
9 (I)	H	H	CF3	H	F	H	H	H	—	Active	>100
10 (I)	H	H	H	CF3	F	H	H	H	—	Active	19.6b
11 (I)	CF3	H	H	H	H	H	Cl	H	—	Active	>100
12 (I)	H	CF3	H	H	H	H	Cl	H	—	Active	>100
13 (I)	H	H	CF3	H	H	H	Cl	H	—	Active	>100
14 (I)	H	H	H	CF3	H	H	Cl	H	—	Active	11.9b
15 (I)	H	H	H	CF3	H	Cl	H	H	—	Active	1.5b
16 (I)	H	H	H	CF3	H	Cl	Cl	H	—	Active	10.7b
17 (I)	H	H	H	CF3	H	F	H	H	—	Active	12.3b
18 (I)	H	H	H	CF3	H	H	F	H	—	Active	13.1b
19 (I)	H	H	H	CF3	H	Me	H	H	—	Active	8.4b
20 (I)	H	H	H	CF3	H	H	Me	H	—	Active	32b
21 (II)	H	H	H	CF3	—	—	—	H	Bn	Active	>100
22 (I)	H	H	H	Cl	H	H	H	H	—	Active	>100
23 (I)	H	Cl	H	H	F	H	H	H	—	Active	>100
24 (I)	Cl	H	H	H	H	H	Cl	H	—	Active	>100
25 (I)	H	H	H	Cl	H	H	Cl	H	—	Active	15.0b
26 (I)	H	H	H	Cl	H	Cl	H	H	—	Active	>100
27 (I)	H	H	H	Cl	H	F	H	H	—	Active	>100
28 (I)	H	H	Me	H	H	H	Cl	H	—	Active	>100b
29 (I)	H	H	H	Br	H	H	H	H	—	Active	>100
30 (I)	H	H	H	Br	H	H	Cl	H	—	Active	49.5b

^aFor explanation of prescreen refer to text; for summary of inactive compounds refer to Table S1.

^bIC₅₀ values correspond to those reported previously⁹ for compounds 8, 10, 14–20, 25, 28, and 30; corresponding to MPD compounds 19, 20, 37, 131, 162, 134, 137, 140, 146, 32, 39, and 159, respectively, in Ref. 9.