2. Academic Validation
  3. N-Phenyl-1-(phenylsulfonyl)-1 H-1,2,4-triazol-3-amine as a New Class of HIV-1 Non-nucleoside Reverse Transcriptase Inhibitor

N-Phenyl-1-(phenylsulfonyl)-1 H-1,2,4-triazol-3-amine as a New Class of HIV-1 Non-nucleoside Reverse Transcriptase Inhibitor

  • J Med Chem. 2023 May 11;66(9):6193-6217. doi: 10.1021/acs.jmedchem.2c02055.
Thomas Lane 1,  Vadim Makarov 2,  Julie A E Nelson 3,  Rick B Meeker 4,  Giuseppina Sanna 5,  Olga Riabova 2,  Elena Kazakova 2,  Natalia Monakhova 2,  Andrey Tsedilin 2,  Fabio Urbina 1,  Thane Jones 1,  Ashley Suchy 3,  Sean Ekins 1
Affiliations

Affiliations

  • 1 Collaborations Pharmaceuticals Inc., 840 Main Campus Drive, Lab 3510, Raleigh, North Carolina 27606, United States.
  • 2 Research Center of Biotechnology RAS, Leninsky Prospekt 33-2, 119071, Moscow 119071, Russia.
  • 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.
  • 5 Department of Biomedical Science, University of Cagliari, Monserrato 09042, Italy.
PMID: 37130343 DOI: 10.1021/acs.jmedchem.2c02055
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.

Figures
Products
嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z