Journal of Medicinal Chemistry, volume 66, issue 9, pages 6193-6217
N-Phenyl-1-(phenylsulfonyl)-1H-1,2,4-triazol-3-amine as a New Class of HIV-1 Non-nucleoside Reverse Transcriptase Inhibitor
Lane Thomas R.
1
,
Makarov Vadim
2
,
Nelson Julie A.E.
3
,
Meeker Rick B.
4
,
Sanna Giuseppina
5
,
Riabova Olga
2
,
Kazakova Elena
2
,
Monakhova Natalia
2
,
Tsedilin Andrey
2
,
Urbina Fabio
1
,
Jones Thane
1
,
Suchy Ashley
3
,
1
Collaborations Pharmaceuticals Inc., 840 Main Campus Drive, Lab 3510, Raleigh, North Carolina 27606, United States
|
3
Department of Microbiology and Immunology, University of North Carolina, Chapel Hill, North Carolina 27599, United States
|
4
Department of Neurology, University of North Carolina, Chapel Hill, North Carolina 27599, United States
|
Publication type: Journal Article
Publication date: 2023-05-02
Journal:
Journal of Medicinal Chemistry
Quartile SCImago
Q1
Quartile WOS
Q1
Impact factor: 7.3
ISSN: 00222623, 15204804
Drug Discovery
Molecular Medicine
Abstract
Highly active antiretroviral therapy (HAART) has revolutionized human immunodeficiency virus (HIV) healthcare, turning it from a terminal to a potentially chronic disease, although some patients can develop severe comorbidities. These include neurological complications, such as HIV-associated neurocognitive disorders (HAND), which result in cognitive and/or motor function symptoms. We now describe the discovery, synthesis, and evaluation of a new class of N-phenyl-1-(phenylsulfonyl)-1H-1,2,4-triazol-3-amine HIV-1 non-nucleoside reverse transcriptase inhibitors (NNRTI) aimed at avoiding HAND. The most promising molecule, 12126065, exhibited antiviral activity against wild-type HIV-1 in TZM cells (EC50 = 0.24 nM) with low in vitro cytotoxicity (CC50 = 4.8 μM) as well as retained activity against clinically relevant HIV mutants. 12126065 also demonstrated no in vivo acute or subacute toxicity, good in vivo brain penetration, and minimal neurotoxicity in mouse neurons up to 10 μM, with a 50% toxicity concentration (TC50) of >100 μM, well below its EC50.
Citations by journals
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1
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Drug Discovery Today
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Drug Discovery Today
1 publication, 25%
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ACS Omega
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ACS Omega
1 publication, 25%
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RSC Advances
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RSC Advances
1 publication, 25%
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Bioorganic Chemistry
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Bioorganic Chemistry
1 publication, 25%
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1
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Citations by publishers
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1
2
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Elsevier
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Elsevier
2 publications, 50%
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American Chemical Society (ACS)
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American Chemical Society (ACS)
1 publication, 25%
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Royal Society of Chemistry (RSC)
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Royal Society of Chemistry (RSC)
1 publication, 25%
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1
2
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- We do not take into account publications that without a DOI.
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Lane T. R. et al. N-Phenyl-1-(phenylsulfonyl)-1H-1,2,4-triazol-3-amine as a New Class of HIV-1 Non-nucleoside Reverse Transcriptase Inhibitor // Journal of Medicinal Chemistry. 2023. Vol. 66. No. 9. pp. 6193-6217.
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Lane T. R., Makarov V., Nelson J. A., Meeker R. B., Sanna G., Riabova O., Kazakova E., Monakhova N., Tsedilin A., Urbina F., Jones T., Suchy A., Ekins S. N-Phenyl-1-(phenylsulfonyl)-1H-1,2,4-triazol-3-amine as a New Class of HIV-1 Non-nucleoside Reverse Transcriptase Inhibitor // Journal of Medicinal Chemistry. 2023. Vol. 66. No. 9. pp. 6193-6217.
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TY - JOUR
DO - 10.1021/acs.jmedchem.2c02055
UR - https://doi.org/10.1021%2Facs.jmedchem.2c02055
TI - N-Phenyl-1-(phenylsulfonyl)-1H-1,2,4-triazol-3-amine as a New Class of HIV-1 Non-nucleoside Reverse Transcriptase Inhibitor
T2 - Journal of Medicinal Chemistry
AU - Lane, Thomas R.
AU - Makarov, Vadim
AU - Nelson, Julie A.E.
AU - Meeker, Rick B.
AU - Sanna, Giuseppina
AU - Riabova, Olga
AU - Kazakova, Elena
AU - Monakhova, Natalia
AU - Tsedilin, Andrey
AU - Urbina, Fabio
AU - Jones, Thane
AU - Suchy, Ashley
AU - Ekins, Sean
PY - 2023
DA - 2023/05/02 00:00:00
PB - American Chemical Society (ACS)
SP - 6193-6217
IS - 9
VL - 66
SN - 0022-2623
SN - 1520-4804
ER -
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@article{2023_Lane,
author = {Thomas R. Lane and Vadim Makarov and Julie A.E. Nelson and Rick B. Meeker and Giuseppina Sanna and Olga Riabova and Elena Kazakova and Natalia Monakhova and Andrey Tsedilin and Fabio Urbina and Thane Jones and Ashley Suchy and Sean Ekins},
title = {N-Phenyl-1-(phenylsulfonyl)-1H-1,2,4-triazol-3-amine as a New Class of HIV-1 Non-nucleoside Reverse Transcriptase Inhibitor},
journal = {Journal of Medicinal Chemistry},
year = {2023},
volume = {66},
publisher = {American Chemical Society (ACS)},
month = {may},
url = {https://doi.org/10.1021%2Facs.jmedchem.2c02055},
number = {9},
pages = {6193--6217},
doi = {10.1021/acs.jmedchem.2c02055}
}
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MLA
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Lane, Thomas R., et al. “N-Phenyl-1-(phenylsulfonyl)-1H-1,2,4-triazol-3-amine as a New Class of HIV-1 Non-nucleoside Reverse Transcriptase Inhibitor.” Journal of Medicinal Chemistry, vol. 66, no. 9, May. 2023, pp. 6193-6217. https://doi.org/10.1021%2Facs.jmedchem.2c02055.
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