Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2012 Feb 15;22(4):1565-8.
doi: 10.1016/j.bmcl.2011.12.132. Epub 2012 Jan 5.

Discovery of dimeric inhibitors by extension into the entrance channel of HIV-1 reverse transcriptase

Anil R Ekkati  1 , Mariela Bollini, Robert A Domaoal, Krasimir A Spasov, Karen S Anderson, William L Jorgensen
Affiliations

Discovery of dimeric inhibitors by extension into the entrance channel of HIV-1 reverse transcriptase

Anil R Ekkati et al. Bioorg Med Chem Lett. .

Abstract

Design of non-nucleoside inhibitors of HIV-1 reverse transcriptase is being pursued with computational guidance. Extension of azine-containing inhibitors into the entrance channel between Lys103 and Glu138 has led to the discovery of potent and structurally novel derivatives including dimeric inhibitors in an NNRTI-linker-NNRTI motif.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Rendering of the 2be2 crystal structure of 4 bound to HIV-RT. Carbon atoms of 4 are in green. Some residues are omitted for clarity.
Figure 2
Figure 2
Computed structure of 5d bound to HIV-RT illustrating extension of the polyether side chain into the entrance channel. Carbon atoms of 5d are in green. Some residues are omitted for clarity.
Figure 3
Figure 3
Computed structure of 6b bound to HIV-RT illustrating extension into the entrance channel. Carbon atoms of the inhibitor are in green. Some residues are omitted for clarity.
Scheme 1
Scheme 1
Synthesis of substituted triazenes.
Scheme 2
Scheme 2
Synthesis of dimeric inhibitors.
See this image and copyright information in PMC

References

    1. Flexner C. Nature Rev Drug Disc. 2007;6:959. - PubMed
    1. Kohlstaedt LA, Wang J, Friedman JM, Rice PA, Steitz TA. Science. 1992;256:1783. - PubMed
    1. Prajapati DG, Ramajayam R, Yadav MR, Giridhar R. Bioorg Med Chem. 2009;17:5744. - PubMed
    1. De Clerq E. Nature Rev Drug Disc. 2007;6:1001. - PubMed
    1. Adams J, Patel N, Mankaryous N, Tadros M, Miller CD. Ann Pharmacotherapy. 2010;44:157. - PubMed

Publication types

MeSH terms

Substances