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Rational design of potent non-nucleoside inhibitors of HIV-1 reverse transcriptase.

Abstract：

:A new series of non-nucleoside reverse transcriptase inhibitors based on an imidazole-amide biarylether scaffold has been identified and shown to possess potent antiviral activity against HIV-1, including the NNRTI-resistant Y188L mutated virus. X-ray crystallography of inhibitors bound to reverse transcriptase, including a structure of the Y188L RT protein, was used extensively to help identify and optimize the key hydrogen-bonding motif. This led directly to the design of compound 43 that exhibits remarkable antiviral activity (EC50<1 nM) against a wide range of NNRTI-resistant viruses and a favorable pharmacokinetic profile across multiple species.

journal_name

J Med Chem

journal_title

Journal of medicinal chemistry

authors

Chong P,Sebahar P,Youngman M,Garrido D,Zhang H,Stewart EL,Nolte RT,Wang L,Ferris RG,Edelstein M,Weaver K,Mathis A,Peat A

doi

10.1021/jm301294g

subject

Has Abstract

pub_date

2012-12-13 00:00:00

pages

10601-9

issue

23

eissn

0022-2623

issn

1520-4804

journal_volume

55

pub_type

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