Journal article

Optimization of 5-substituted thiazolyl ureas and 6-substituted imidazopyridines as potential HIV-1 latency reversing agents

William Nguyen, Jonathan Jacobson, Kate E Jarman, Timothy R Blackmore, Helene Jousset Sabroux, Sharon R Lewin, Damian F Purcell, Brad E Sleebs

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER | Published : 2020

Abstract

A persistent latent reservoir of virus in CD4+ T cells is a major barrier to cure HIV. Activating viral transcription in latently infected cells using small molecules is one strategy being explored to eliminate latency. We previously described the use of a FlpIn.FM HEK293 cellular assay to identify and then optimize the 2-acylaminothiazole class to exhibit modest activation of HIV gene expression. Here, we implement two strategies to further improve the activation of viral gene expression and physicochemical properties of this class. Firstly, we explored rigidification of the central oxy-carbon linker with a variety of saturated heterocycles, and secondly, investigated bioisosteric replaceme..

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Grants

Awarded by National Health and Medical Research Council of Australia


Funding Acknowledgements

This work was funded by the National Health and Medical Research Council of Australia (Development Grant 1113712 to D.F.P., B.E.S. and S.R.L.; Project Grant 1129320 to D.F.P. and B.E.S.; Program Grant 1052979 to D.F.P. and S.R.L.; Practitioner Fellowship to S.R.L.), the Australian Centre for HIV and Hepatitis Virology Research, the Australian Cancer Research Foundation, the Victorian State Government Operational Infrastructure Support and Australian Government NHMRC IRIISS. B.E.S. is a Corin Centenary Fellow.