Table 1.

Chemical structures of conformationally constrained bicyclic Smac mimetics and their binding affinities to XIAP BIR3.

Compounds	X	R1	R2	R3	XIAP BIR3 Ki (μM)
AVPI					0.5823
1					0.2923
2	CH2	Me	NH2	Bn	4.4724
3					>10024
4	(CH2)2	Me	NH2	Bn	0.1523
5	(CH2)3	Et	NH2	Bn	0.10
6	CH2	Et	NH2	Bn	1.41 ± 0.16
7	CH2	n-Pr	NH2	Bn	>100
8	CH2	i-Pr	NH2	Bn	43.11 ± 1.51
9	CH2	Me	NH2		2.33 ± 0.68
10	CH2	Et	NH2		0.35 ± 0.01
11	(CH2)2	Me	NH2		0.06 ± 0.02
12	(CH2)2	Et	NH2		0.025 ± 0.004
13	(CH2)2	Et	MeNH		0.061 ± 0.006
14	(CH2)2	Et	Me2N		14.4 ± 0.6
15	(CH2)2	Et	OH		29.0 ± 1.4
16	(CH2)3	Me	NH2		0.014 ± 0.003
17	(CH2)3	Et	NH2		0.039 ± 0.004
18	(CH2)3	Et	NH2		0.759 ± 0.16
19	(CH2)3	Et	NH2		0.047 ± 0.009
20	(CH2)3	Me	MeNH		0.026 ± 0.005
21	(CH2)3	Et	MeNH		0.067 ± 0.018
22	(CH2)3	Et			0.856 ± 0.075
23	(CH2)3	Et			32.87 ± 4.18
24	(CH2)3	Me	OH		12.97 ± 2.02
25	(CH2)3	Me	MeNH		0.014 ± 0.005
26	(CH2)3	Me	MeNH		0.274 ± 0.037
27	(CH2)3	Me	MeNH		0.015 ± 0.008