Novel indole based NNRTIs with improved potency against wild type and resistant HIV

Bioorg Med Chem Lett. 2014 Sep 15;24(18):4376-4380. doi: 10.1016/j.bmcl.2014.08.020.

Ronel Müller ¹, Iqbal Mulani ¹, Adriaan E Basson ², Nicole Pribut ¹, Mohammad Hassam ¹, Lynn Morris ², Willem A L van Otterlo ¹, Stephen C Pelly ³

Affiliations

1 Department of Chemistry and Polymer Science, Stellenbosch University, Private Bag X1, 7602 Matieland, Western Cape, South Africa.
2 AIDS Virus Research Unit, National Institute for Communicable Diseases, Private Bag X4, Sandringham 2131, Johannesburg, South Africa.
3 Department of Chemistry and Polymer Science, Stellenbosch University, Private Bag X1, 7602 Matieland, Western Cape, South Africa. Electronic address: scpelly@sun.ac.za.

PMID: 25176191 DOI: 10.1016/j.bmcl.2014.08.020

Abstract

The human immunodeficiency virus (HIV) pandemic remains a significant problem, especially in developing nations where the social and economic impacts are severe. Until a cure or vaccine for the disease is found, a constant supply of new compounds to fill the drug development pipeline is a requirement, given the tendency for the virus to rapidly develop resistance to current therapies. Here we disclose our efforts to improve upon the efficacy of cyclopropyl-indole derivatives developed as NNRTIs in our laboratories. To this end, modifications to the functionality occupying the small Val179 pocket have resulted in nearly two orders of magnitude increase in potency.

Keywords

AIDS; HIV; Indole; NNRTIs.

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