Table 1.

Cytotoxicity, Enzymatic, and Antiviral Activities of Compounds 7a–y and 8a–y

							activity in enzyme assay, IC50a		antiviral activity
compd	R2	R3	R4	R5	R6	X	RHb	STc	EC50d HeLa	EC50e MT-4	CC50f	SIg
7a	H	H	H	H	H	Et		15	0.25	1.5	41	164
7b	Me	H	H	H	H	Et	3.0	32	1.4		>50	>35
7c	H	Me	H	H	H	Et	9.6	8.0	2.4	2.2	37	15
7d	H	H	Me	H	H	Et	7.3	>111	17.4		>50	>2
7e	F	H	H	H	H	Et	6.3	1.0	0.31	1.2	>50	>161
7f	H	F	H	H	H	Et	9.0	11	2.2	5.4	42	19
7g	H	H	F	H	H	Et	8	98	<0.2	1.7	>50	>250
7h	H	Cl	H	H	H	Et	19	6	0.79		>50	>63
7i	H	H	Cl	H	H	Et	8.0	42	26.3		>50	>1
7j	CN	H	H	H	H	Et	32	9.0	17		>50	>2
7k	H	CN	H	H	H	Et	5	13	7.1		48	7
7l	H	H	CN	H	H	Et	8	>111	>50		>50
7m	OMe	H	H	H	H	Et	>100	23	0.2		>50	>250
7n	H	H	OMe	H	H	Et	6.7	110	>50		>50
7o	OEt	H	H	H	H	Et	>100	12	0.6		>50	>83
7p	H	Me	H	Me	H	Et	6	19	13.8		>50	>3
7q	F	F	H	H	H	Et	8	0.53	<0.2		>50	>250
7r	F	H	F	H	H	Et	19	1.00	<0.2		>50	>250
7s	F	H	H	F	H	Et	9	0.45	0.81		>50	>16
7t	F	H	H	H	F	Et	19	4.00	0.2		>50	>250
7u	H	F	F	H	H	Et	3	0.60	2		>50	>25
7v	H	F	H	F	H	Et	5	0.49	3.9		>50	>12
7w	Cl	H	Cl	H	H	Et	9	>111	>50		>50
7x	Cl	H	H	H	Cl	Et	22	1.70	2.5		>50	>20
7y	H	Cl	H	Cl	H	Et		8.0	3		30	10
8a	H	H	H	H	H	H	15	0.09	0.35	0.83	>50	>142
8b	Me	H	H	H	H	H	26	0.17	3.7	1.6	>50	>13
8c	H	Me	H	H	H	H	4.6	1.3	1.9	4.7	>50	>26
8d	H	H	Me	H	H	H	17	1.2	>50		>50
8e	F	H	H	H	H	H	6.4	0.98	0.35		>50	>142
8f	H	F	H	H	H	H	14	0.92	5.1	2.6	>50	>9
8g	H	H	F	H	H	H	2.5	0.026	0.63	1.7	>50	>79
8h	H	Cl	H	H	H	H	9	0.31	>50		>50
8i	H	H	Cl	H	H	H	5.0	4.1	>50	>50	>50
8j	CN	H	H	H	H	H	6	6	>50		>50
8k	H	CN	H	H	H	H	5	0.75	>50		>50
8l	H	H	CN	H	H	H	6	1.7	>50		>50
8m	OMe	H	H	H	H	H	16	0.53	<0.2		42	>210
8n	H	H	OMe	H	H	H	3.0	4.1	17.4		>50	>2
8o	OEt	H	H	H	H	H	64	0.31	<0.2		>50	>250
8p	H	Me	H	Me	H	H	16	1.6	9.8		30	3
8q	F	F	H	H	H	H	6	0.059	0.52		>50	>128
8r	F	H	F	H	H	H	10	0.042	0.5		44	88
8s	F	H	H	F	H	H	5	0.052	2.5		>50	>20
8t	F	H	H	H	F	H	50	0.15	<0.2		>50	>250
8u	H	F	F	H	H	H	86	1.60	>50		>50
8v	H	F	H	F	H	H	14	1.2	1.7		>50	>29
8w	Cl	H	Cl	H	H	H	7	4.9	16.2		>50	>3
8x	Cl	H	H	H	Cl	H	28	0.17	1.4		>50	>35
8y	H	Cl	H	Cl	H	H	30	0.97	>50		>50
1								0.007	0.024	0.016	>250	>15000
2							3.2	1.9	ND	>50

^aInhibitory concentration 50% (μM) determined from dose–response curves.

^bExperiments performed against HIV-1 RT-associated RNase H activity.

^cExperiments performed against HIV-1 IN ST activity.

^dEffective concentration 50% (μM) in HIV-1 infected HeLa cells.

^eEffective concentration 50% (μM) in HIV-1 infected MT-4 cells.

^fCytotoxic concentration 50% (μM).

^gSelectivity index = CC₅₀/EC₅₀ in HeLa cells.