Arylazolyl(azinyl)thioacetanilides. Part 16: Structure-based bioisosterism design, synthesis and biological evaluation of novel pyrimidinylthioacetanilides as potent HIV-1 inhibitors.

Abstract:

:A series of novel pyrimidinylthioacetanilides were designed, synthesized, and evaluated for their biological activity as potent HIV-1 non-nucleoside reverse transcriptase inhibitors (NNRTIs). Most of the tested compounds were proved to be effective in inhibiting HIV-1 (IIIB) replication with EC50 ranging from 0.15 μM to 24.2 μM, thereinto compound 15 was the most active lead with favorable inhibitory activity against HIV-1 (IIIB) (EC50=0.15 μM, SI=684). Besides, compound 6 displayed moderate inhibition against the double-mutated HIV-1 strain (K103N/Y181C) (EC50=3.9 μM). Preliminary structure-activity relationships (SARs), structure-cytotoxicity relationships (SCRs) data, and molecular modeling studies were discussed as well, which may provide valuable insights for further optimizations.

journal_name

Bioorg Med Chem

authors

Li X,Lu X,Chen W,Liu H,Zhan P,Pannecouque C,Balzarini J,De Clercq E,Liu X

doi

10.1016/j.bmc.2014.08.001

subject

Has Abstract

pub_date

2014-10-01 00:00:00

pages

5290-7

issue

19

eissn

0968-0896

issn

1464-3391

pii

S0968-0896(14)00577-X

journal_volume

22

pub_type

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