. Author manuscript; available in PMC: 2012 May 4.

Published in final edited form as: J Med Chem. 2010 Nov 4;53(23):8287–8297. doi: 10.1021/jm100738d

Table 2.

Data against HIV drug-resistant viral strain replication


	R₁	R₂	R₃	HIV-1 RTMDR^a in TZM-bl cell line		A17 ^b in MT-2 cell line

				EC₅₀ (μM)	RF^c	EC₅₀(μM)	RF
11a	H	I	NO₂	0.0943 ± 0.009	1.55	>10	>127
13a	H	I	NH₂	0.00513 ± 0.00115	0.67	1.93 ± 0.06	36
11b	H	Br	NO₂	0.0776 ± 0.0137	1.55	>10	>222
13b	H	Br	NH₂	0.0068 ± 0.0030	0.93	3.49 ± 0.46	106
11f	H	C≡CH	NO₂	0.215 ± 0.033	1.94	>10	>40
13f	H	C≡CH	NH₂	0.0090 ± 0.002	1.34	1.43 ± 0.26	34
11m	H	CH=CHCN	NO₂	0.0148 ± 0.0024	1.85	>10	>204
13m	H	CH=CHCN	NH₂	0.00059 ± 0.00009	0.83	0.20 ± 0.01	14
13c	H	CH₂CH=CH₂	NH₂	0.0154 ± 0.0016	2.23	>10	>149
13e	H	C≡CCH(CH₂)₂	NH₂	0.121 ± 0.0177	1.33	>10	>24
13k	H	CH₂CH₂COMe	NH₂	0.0032 ± 0.0008	1.64	0.73 ± 0.058	13
12c	H	CH=CHCN	NO₂	0.0170 ± 0.0011	1.63	>10	>270
14c	H	CH=CHCN	NH₂	0.00179 ± 0.0013	3.25	0.60 ± 0.09	43
14e	NO₂	CH=CHCN	NH₂	0.00087 ± 0.0001	2.29	0.095 ± 0.001	6.79
14f	NH₂	CH=CHCN	NH₂	0.0020 ± 0.0003	0.47	3.05 ± 0.03	128
3	H	C≡N	NH₂	0.00096 ± 0.0003	1.41	0.39 ± 0.065	26
1				0.0010 ± 0.0004	0.71	0.33 ± 0.02	6.00

Each compound was tested at least in triplicate.

HIV-1 RTMDR (obtained from AIDS Research and Reference Reagent Program, Division of AIDS, NIAID, NIH), which contains mutations in RT amino acid residues L74V, M41L, V106A, and T215Y, is resistant to AZT, ddI, nevirapine, and other non-nucleoside RT inhibitors.

The multi-NRTI-resistant strain A17 from NIH with mutations at amino acids K103N and Y181C in the viral RT domain is highly resistant to NRTIs.¹⁹

Resistant fold.