. Author manuscript; available in PMC: 2021 Jul 29.

Published in final edited form as: J Med Chem. 2015 May 26;58(11):4610–4623. doi: 10.1021/acs.jmedchem.5b00159

Table 1.

Cytotoxicity, Antiviral, Anti-IN, and Anti-RNase H Activities of Compounds 10a–w and 11a–w


								activity in enzyme assays
								IN IC₅₀ (μM)^a		RNase H		antiviral activity and cytotoxicity
compd	R	R₂	R₃	R₄	R₅	R₆	X	3′-P	ST	% in. at 10 μM^b	IC₅₀ (μM)	EC₅₀ (μM)^c	CC₅₀ (μM)^d	SI^e
10a		H	H	H	H	H	Et	>1000	0.70	−3.3	nd^f	1	>50	>50
10b		F	H	H	H	H	Et	125	0.28	2.8	nd	1.5	>50	>33.4
10c		och₃	H	H	H	H	Et	>333	1.4	11.4	nd	2.6	>50	>19.2
10d		H	F	H	H	H	Et	>12.3	4.9	−9.4	nd	1.7	>50	>29.4
10e		H	OCH₃	H	H	H	Et	>333	16	4.9	nd	8.5	44	5.2
10f		H	H	Cl	H	H	Et	>37	>37	16.1	nd	>50	nd
10g		H	H	OH	H	H	Et	>333	1.4	26.0	nd	30.9	>50	>1.6
10h		H	H	och₃	H	H	Et	>37	>37	10.0	nd	>50	nd
10i		H	H	NO₂	H	H	Et	>37	>37	31.9	nd	>50	nd
10j		F	H	F	H	H	Et		2.2	3	nd	0.58	>50	>86.2
10k		F	H	H	F	H	Et		3.7	30	nd	>50	nd
10l		F	H	H	H	F	Et	>12.3	0.25	4.1	nd	<0.2	>50	>250
10m		H	F	F	H	H	Et		5.5	24	nd	9.8	>50	>5.1
10n		H	F	H	F	H	Et		11	24	nd	32.4	>50	>1.5
10o		Cl	H	Cl	H	H	Et		>111	51	>50	>50	nd
10p		Cl	H	H	H	Cl	Et		32	55.0	>50	30.2	>50	>1.7
10q		ch₃	H	ch₃	H	H	Et		>111	33	>50	>50	nd
10r		H	CH₃	H	CH₃	H	Et		1.3	21	nd	>50	nd
10s		F	Cl	H	H	H	Et	1.08	1.08	21	nd	10	>50	>5
10t		H	Cl	F	H	H	Et	266	3.1	18	nd	17.4	>50	>2.9
10u	8-Cl	H	Cl	F	H	H	Et	>333	25.08	24	nd	>50	nd
10w	7-Cl	F	H	H	H	H	Et			2.8	nd	11	>50	>4.5
11a		H	H	H	H	H	H	4.0	0.034	9.6	nd	15.5	>50
11b		F	H	H	H	H	H	1.2	0.016	45.1	>50	2.6	>50	>19.2
11c		OCH₃	H	H	H	H	H	>4.1	0.038	45.2	16.3 ± 0.5	9.3	>50	>5.4
11d		H	F	H	H	H	H	4.6	0.015	2.4	nd	28.2	>50	>1.8
11e		H	och₃	H	H	H	H	>4.1	0.14	1.9	nd	>50	nd
11f		H	H	Cl	H	H	H	22	0.54	56.2	>50	0.87	>50	>57.5
11g		H	H	OH	H	H	H	>37	0.45	44.4	9.5 ± 0.4	>50	nd
11h		H	H	OCH₃	H	H	H	28	0.51	45.8	>50	>50	nd
11i		H	H	no₂	H	H	H	27	0.64	42.4	47.0 ± 1.5	>50	nd
11j		F	H	F	H	H	H		0.010	46	35.9 ± 0.8	13.8	>50	>3.6
11k		F	H	H	F	H	H		3.2	37	>50	>50	nd
11l		F	H	H	H	F	H	0.7	0.019	57.9	10.8 ± 0.4	8.1	>50	>6.2
11m		H	F	F	H	H	H		0.11	44	>50	16.2	>50	>3.1
11n		H	F	H	F	H	H		0.22	30	>50	>50	nd
11o		Cl	H	Cl	H	H	H		2.3	68	44.7 ± 2.0	>50	nd
11p		Cl	H	H	H	Cl	H		0.27	86.3	10.0 ± 0.3	>50	nd
11q		ch₃	H	ch₃	H	H	H		7.0	52	19.6 ± 0.6	>50	nd
11r		H	ch₃	H	ch₃	H	H		0.05	47	37.8 ± 0.9	>50	nd
11s		F	Cl	H	H	H	H	1.75	0.018	12	nd	23.4	>50	>2.1
11t		H	Cl	F	H	H	H	21	0.19	25	nd	>50	nd
11u	8-Cl	H	Cl	F	H	H	H	9.8	0.096	16	nd	50	nd
11v	8-Cl	F	H	H	H	H	H	20.5	0.13	45	>50	>50	nd
11w	7-Cl	F	H	H	H	H	H			36.5	22.6 ± 0.5	17	>50	>2.9
1								12.8 ± 6^g	0.087 ± 0.008^h	nd	>100	0.0236 ± 0.0046	>50	>2118
EVG								8.1 ± 4.2^g	0.028 ± 0.006^g	nd	91 ± 8	0.0142 ± 0.0052	>50	>3521

Inhibitory concentration 50% (μM) determined from dose response curves.

Percentage of inhibition determined at compound concentration of 10 μM.

Effective concentration 50% (μM).

Cytotoxic concentration 50% (μM).

SI = CC₅₀/EC₅₀.

nd: not determined.

Reference 20.

Reference 18.