Design and synthesis of tetrahydrophthalimide derivatives as inhibitors of HIV-1 reverse transcriptase

Organic and Medicinal Chemistry Letters

Table 1 Binding free energy and predicted inhibitory constant values of the synthesized compounds

Serial	Compound	R	Binding	Inhibitory
number	code		free energy	constant (nM)
			(Kcal/mole)
1	Efavirenz	-	−12.02	1.56
	(standard)
2	TNK-651	-	−11.88	1.95
3	4a	H	−8.13	1,100.0
4	4b	4-OCH₃	−7.65	2,460.0
5	4c	4-CH₃	−8.5	588.3
6	4d	4-Cl	−7.79	1,930.0
7	4e	3-OCH₃	−8.62	479.1
8	4f	3-CH₃	−8.61	484.7
9	4g	3-Cl	−8.87	315.7
10	4h	2-OCH₃	−7.94	1,510.0
11	4i	2-CH₃	−8.2	975.83
12	4j	2-Cl	−8.2	975.83
13	4k	4-NO ₂	−10.53	19.11
14	4l	3-NO ₂	−10.89	10.38
15	4m	2-NO ₂	10.46	22.86
16	4n	2,4-diCH₃	−8.87	313.63
17	4o	3,4-diCH ₃	10.49	20.37
18	4p	2-Cl, 3-CH ₃	−10.71	14.2

4k, 4l, 4m, 4o, and 4p showed satisfactory and comparable docking results as that of standard drug efavirenz and TNK-651 (the same thing has been discussed under the subsection “In vitro HIV-1 RT inhibitory activity” of the “Results and discussion” section).