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. 2010 Apr 15;20(8):2485-8.
doi: 10.1016/j.bmcl.2010.03.006. Epub 2010 Mar 4.

Eastern extension of azoles as non-nucleoside inhibitors of HIV-1 reverse transcriptase; cyano group alternatives

Cheryl S Leung  1 , Jacob G Zeevaart, Robert A Domaoal, Mariela Bollini, Vinay V Thakur, Krasimir A Spasov, Karen S Anderson, William L Jorgensen
Affiliations

Eastern extension of azoles as non-nucleoside inhibitors of HIV-1 reverse transcriptase; cyano group alternatives

Cheryl S Leung et al. Bioorg Med Chem Lett. .

Abstract

Design of non-nucleoside inhibitors of HIV-1 reverse transcriptase is being pursued with the assistance of free energy perturbation (FEP) calculations to predict relative free energies of binding. Extension of azole-containing inhibitors into an 'eastern' channel between Phe227 and Pro236 has led to the discovery of potent and structurally novel derivatives.

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Figures

Scheme 1
Scheme 1
Scheme 2
Scheme 2
Figure 1
Figure 1
Snapshot of 1e bound to HIV-RT from a MC/FEP simulation. Carbon atoms of 1e are in yellow. Some residues including His235, Pro236 and Tyr318 are omitted for clarity.
Figure 2
Figure 2
Complex for 3n built with BOMB and energy-minimized.
See this image and copyright information in PMC

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