Design, synthesis, and biological evaluations of novel quinolones as HIV-1 non-nucleoside reverse transcriptase inhibitors

David Ellis; Kelli L Kuhen; Beth Anaclerio; Baogen Wu; Karen Wolff; Hong Yin; Badry Bursulaya; Jeremy Caldwell; Donald Karanewsky; Yun He

doi:10.1016/j.bmcl.2006.05.073

Design, synthesis, and biological evaluations of novel quinolones as HIV-1 non-nucleoside reverse transcriptase inhibitors

Bioorg Med Chem Lett. 2006 Aug 15;16(16):4246-51. doi: 10.1016/j.bmcl.2006.05.073. Epub 2006 Jun 16.

Authors

David Ellis¹, Kelli L Kuhen, Beth Anaclerio, Baogen Wu, Karen Wolff, Hong Yin, Badry Bursulaya, Jeremy Caldwell, Donald Karanewsky, Yun He

Affiliation

¹ Genomics Institute of the Novartis Research Foundation (GNF), San Diego, CA 92121, USA.

PMID: 16782337
DOI: 10.1016/j.bmcl.2006.05.073

Abstract

A novel series of quinolones was discovered as HIV-1 non-nucleoside reverse transcriptase inhibitors (NNRTIs) using a structure-based approach. The lead quinolones exhibited single digit nanomolar potency in the HIV-1 replication assays. The preliminary SAR of these quinolones was also established via systematic structural modifications. These novel and potent quinolones could serve as advanced leads for further optimization.

MeSH terms

Binding Sites
Drug Resistance, Viral
HIV Reverse Transcriptase / antagonists & inhibitors
HIV-1 / metabolism
Models, Chemical
Models, Molecular
Mutation
Quinolones / chemistry
Reverse Transcriptase Inhibitors / pharmacology*
Structure-Activity Relationship
Virus Replication

Substances

Quinolones
Reverse Transcriptase Inhibitors
HIV Reverse Transcriptase