Table 2. MDM2 and MDMX structure–activity relationships for triarylpyrroles 4c and 4m–z .

Compound	R1	R2	X	Y	MDM2 IC50 (μM) a	MDMX IC50 (μM) a
4c	H	H	Cl	S	0.11 ± 0.03	4.2 ± 1.2
4m	H	H	Cl	O	0.30 ± 0.03	nd
4n	H	H	Br	O	0.18 ± 0.07	nd
4o	H	H	OMe	O	1.9 ± 0.3	13 ± 7
4p	H	H	t-Bu	O	1.9 ± 0.3	nd
4q	H	H	CN	O	4.7 ± 1.9	7.0 ± 3.0
4r	H	H	CN	S	0.20 ± 0.07 d	0.90 ± 0.42
4s	H	H	NO2	O	0.15 ± 0.06	0.68 ± 0.18
4t	H	H	NO2	S	0.17 ± 0.09 d	0.63 ± 0.12
4u	Et	Et	Cl	S	0.30 ± 0.12 c	nd
4v	Et	Et	Br	O	0.89 ± 0.04	74% b
4w	Et	Et	Br	S	0.26 ± 0.05	nd
4x	Me	H	Cl	S	0.11 ± 0.02 d	28 ± 23
4y	Me	H	Br	O	0.34 ± 0.08	35 ± 20
4z	Me	H	Br	S	0.073 ± 0.002	nd

^a n = 3, from resynthesised material.

^b% inhibition at 50 μM.

^c n = 6.

^d n = 4; nd = not determined.