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Bioorg Med Chem Lett. 2015 Nov 1;25(21):4824-4827. doi: 10.1016/j.bmcl.2015.06.074. Epub 2015 Jul 9.

Discovery and crystallography of bicyclic arylaminoazines as potent inhibitors of HIV-1 reverse transcriptase.

Author information

1
Department of Chemistry, Yale University, New Haven, CT 06520-8107, USA.
2
Department of Pharmacology, Yale University School of Medicine, New Haven, CT 06520-8066, USA.
3
Department of Pharmacology, Yale University School of Medicine, New Haven, CT 06520-8066, USA. Electronic address: karen.anderson@yale.edu.
4
Department of Chemistry, Yale University, New Haven, CT 06520-8107, USA. Electronic address: william.jorgensen@yale.edu.

Abstract

Non-nucleoside inhibitors of HIV-1 reverse transcriptase (HIV-RT) are reported that incorporate a 7-indolizinylamino or 2-naphthylamino substituent on a pyrimidine or 1,3,5-triazine core. The most potent compounds show below 10 nanomolar activity towards wild-type HIV-1 and variants bearing Tyr181Cys and Lys103Asn/Tyr181Cys resistance mutations. The compounds also feature good aqueous solubility. Crystal structures for two complexes enhance the analysis of the structure-activity data.

KEYWORDS:

Drug solubility; HIV-1 reverse transcriptase; NNRTI; Protein crystallography; Structure-based drug design

PMID:
26166629
PMCID:
PMC4607639
DOI:
10.1016/j.bmcl.2015.06.074
[Indexed for MEDLINE]
Free PMC Article

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