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

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

doi:10.1016/j.bmcl.2010.03.006

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

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

Authors

Cheryl S Leung¹, Jacob G Zeevaart, Robert A Domaoal, Mariela Bollini, Vinay V Thakur, Krasimir A Spasov, Karen S Anderson, William L Jorgensen

Affiliation

¹ Department of Chemistry, Yale University, New Haven, CT 06520, USA.

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.

Publication types

Research Support, N.I.H., Extramural

MeSH terms

Azoles / chemistry
Azoles / pharmacology*
HIV-1 / enzymology*
Models, Molecular
Reverse Transcriptase Inhibitors / chemistry
Reverse Transcriptase Inhibitors / pharmacology*

Substances

Azoles
Reverse Transcriptase Inhibitors

Abstract

Publication types

MeSH terms

Substances

Grants and funding