Table 1.

Binding of the configurationally constrained indazole-based 4EGI-1 mimetics to eIF4E as measured by fluorescence polarization assay (FP).

Entry	Compound	R1	R2	R3	IC50 (Z)-4EGI-1 /IC50 1a
1	(E)-4EGI-1	NO2	3,4-dichloro	H	0.84±0.07 (41.5)b
2	(Z)-4EGI-1	NO2	3,4-dichloro	H	1.00±0.00 (32.0)b
3	1′a	H	H	H	NAc
4	1′b	H	3,4-dichloro	H	NAc
5	1′c	H	4-OCH3	H	0.40±0.05
6	1a	NO2	H	H	0.82±0.01
7	1b	NO2	3,4-dichloro	H	1.40±0.11
8	1c	NO2	4-OCH3	H	1.70±0.18
9	1d	NO2	3-OCH3	H	4.04±0.52
10	1e	NO2	4-Cl	H	0.91±0.08
11	1f	NO2	2,4-difluoro	H	0.98±0.03
12	1g	NO2	4-F	H	0.61±0.06
13	1h	NO2	H	Me	2.10±0.14
14	1i	NO2	2-OCH3	H	1.92±0.12
15	1j	NO2	2,5-dimethoxy	H	1.05±0.01
16	1k	NO2	2,4-dichloro	H	2.61±0.24
17	1l	NO2	4-pyrrolidine	H	2.70±0.12
18	1m	NO2	4-morpholine	H	2.24±0.05
19	1n	NO2	4-N(Me)2	H	1.81±0.03
20	1o	NO2	4-CO2H	H	2.83±0.07
21	1p	NO2	2-CO2H	H	NAc
22	1q	NO2	2-OH	H	1.02±0.03
23	1r	NO2	3-OH	H	0.75±0.01
24	1s	NO2	4-OH	H	4.12±0.40
25	1t	NO2	3,4-dihydroxy	H	4.09±0.12
26	1u	NO2	3,4-dihydroxy	Me	2.26±0.35

^aThe relative binding affinity of the library of compound 1 as measured by their activity in the fluorescence polarization assay. The relative activity of (Z)-4EGI-1 is given as 1.

^bThe value in brackets is the IC₅₀ in μm.

^cNot active.