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

Won Gil Lee; Kathleen M. Frey; Ricardo Gallardo-Macias; Krasimir A. Spasov; Albert H. Chan; Karen S. Anderson; William L. Jorgensen

doi:10.1016/j.bmcl.2015.06.074

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

Won Gil Lee, Kathleen M. Frey, Ricardo Gallardo-Macias, Krasimir A. Spasov, Albert H. Chan, Karen S. Anderson, William L. Jorgensen

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20 Scopus citations

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.

Original language	English (US)
Pages (from-to)	4824-4827
Number of pages	4
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	25
Issue number	21
DOIs	https://doi.org/10.1016/j.bmcl.2015.06.074
State	Published - Nov 1 2015
Externally published	Yes

Bibliographical note

Publisher Copyright:
© 2015 Elsevier Ltd. All rights reserved.

Keywords

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

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AU - Lee, Won Gil

AU - Frey, Kathleen M.

AU - Gallardo-Macias, Ricardo

AU - Spasov, Krasimir A.

AU - Chan, Albert H.

AU - Anderson, Karen S.

AU - Jorgensen, William L.

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KW - NNRTI

KW - Protein crystallography

KW - Structure-based drug design

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

Abstract

Bibliographical note

Keywords

UN SDGs

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