Design, synthesis and biological evaluation of a series of thioamides as non-nucleoside reverse transcriptase inhibitors

A series of thioamides were designed as bio-isosteres to the non-nucleoside reverse transcriptase inhibitor trovirdine by replacement of the thiourea NH groups with methylene groups. Eight thioamides were synthesized and in vitro tested for inhibitory effects on the activity of HIV-1 reverse transcr...

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Bibliographic Details
Published in:Medicinal chemistry (Shp-sariqah, United Arab Emirates) Vol. 3; no. 6; p. 513
Main Authors: Mehanna, Ahmed S, Belani, Jitendra D, Kelley, Charles J, Pallansc, Luke A
Format: Journal Article
Language:English
Published: Netherlands 01-11-2007
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Summary:A series of thioamides were designed as bio-isosteres to the non-nucleoside reverse transcriptase inhibitor trovirdine by replacement of the thiourea NH groups with methylene groups. Eight thioamides were synthesized and in vitro tested for inhibitory effects on the activity of HIV-1 reverse transcriptase wild and mutant types. Three of the 8-thioamides exhibited enzyme inhibitory activities with IC(50) values below 100 microM. While compound (2) exhibited activity against the mutant strain L100I with IC(50) of 70.1 microM, compound (4) showed activity against the mutant strain K103N with IC(50) of 92.7 microM, and compound (8) with activity against the wild type enzyme with IC(50) of 8.9 microM. Each of the three thioamides could serve as a lead compound for further activity optimization.
ISSN:1573-4064
DOI:10.2174/157340607782360344