Table 1.

Anti-HIV-1 activity, cytotoxicity, and CA hexamer stability profiles of 1–46 (R¹, R² and R³).

Compd	R1	R2	R3	EC50a(μM) or % inhibition at 2 / 20 μM	CC50b (μM)	TSA ΔTm (°C)c
PF74 (1)		Me	Me	0.61 ± 0.2	76 ± 9	7.4
2		Me	Me	0.63 ± 0.1	> 100	8.4
3		Me	Me	0.31 ± 0.1	72 ± 3	9.1
4		Me	Me	0.67 ± 0.03	> 50	7.0
5		Me	Me	0.69 ± 0.01	> 50	6.2
6		Me	Me	0.58 ± 0.2	18 ± 1	5.4
7		Me	Me	1.2 ± 0.7	< 50	7.6
8		Me	Me	> 20	< 100	0
9		Me	Me	> 20	> 100	0
10		Me	Me	3.7 ± 0.4	> 100	3.2
11		H	Me	> 20	40 ± 0.4	0.7
12		H	Me	> 20	> 100	0
13		H	Me	> 20	> 100	−0.6
14		H	Me	> 20	> 100	−0.5
15		H	Me	> 20	> 100	0
16		H	Me	> 20	> 100	0
17		H	Me	11 ± 0.8	15 ± 0.4	−0.6
18		H	Me	10 ± 0.7	49 ± 1	1.4
19		H	Me	> 20	> 100	−0.8
20		H	Me	> 20	> 100	0
21		H	Me	> 20	36 ± 4	0
22		Et	Me	0.25 ± 0.03	82 ± 10	8.5
23		Me	H	0.46 ± 0.1	> 100	6.1
24		Me	H	0.23 ± 0.02	> 100	6.2
25		Me	H	41/97	> 50	1.3
26		Me	H	0.28 ± 0.04	66 ± 6	6.6
27		Me	H	37/98	> 50	1.6
28		Me	H	1.8 ± 0.1	> 100	3.3
29		Me	H	39/97	~ 50	2.5
30		Me	H	0.45 ± 0.05	< 50	4.6
31		Me	H	38/99.5	< 50	4.9
32		Me	H	0.14 ± 0.03	45 ± 7	8.3
33		Me	H	2.0 ± 0.1	<50	3.5
34		Me	H	16/96	< 50	2.8
35		Me	H	2.5 ± 0.2	< 50	2.3
36		Me	H	> 20	> 100	−0.8
37		Me	H	0.26 ± 0.02	57 ± 0.3	4.9
38		H	H	> 20	96 ± 6	0
39		H	H	> 20	> 100	0.8
40		H	H	> 20	> 100	0
41		H	H	> 20	44 ± 0.5	−0.6
42		H	H	> 20	68 ± 9	0
43		H	H	> 20	> 100	−0.7
44		H	H	> 20	> 100	−1.6
45		H	H	> 20	< 100	0.5
46		Et	H	0.44 ± 0.001	70 ± 2	6.4

^aConcentration of compound inhibiting HIV-1 replication by 50%, expressed as the mean ± standard deviation from at least two independent experiments.

^bConcentration of compound causing 50% cell death, expressed as the mean ± standard deviation from at least two independent experiments.

^cTSA: thermal shift assay. ΔTm: change of CA hexamer melting point in presence of compound compared to DMSO control.