Design, synthesis and anti-HIV evaluation of novel diarylpyridine derivatives as potent HIV-1 NNRTIs.

Authors :: Liu Z
Tian Y
Liu J
Huang B
Kang D
De Clercq E
Daelemans D
Pannecouque C
Zhan P
Liu X
Source :: European journal of medicinal chemistry [Eur J Med Chem] 2017 Nov 10; Vol. 140, pp. 383-391. Date of Electronic Publication: 2017 Jul 18.
Publication Year :: 2017
Abstract: As a continuation of our efforts to discover and develop "me-better" drugs of DAPYs, novel diarylpyridine derivatives were designed, synthesized and evaluated for their anti-HIV activities in MT-4 cells. The majority of these compounds showed high activity against wild-type HIV-1 strain (IIIB) with EC <subscript>50</subscript> values in the range of 0.04-4.41 μM. Among them, compound 5b2 (EC <subscript>50</subscript>  = 0.04 μM, SI = 3963) was the most potent. This compound showed anti-HIV-1 <subscript>IIIB</subscript> activity superior than of Nevirapine but still inferior than of Etravirine. Selected compounds were also evaluated for the activity against reverse transcriptase (RT), and most of the compounds exhibited submicromolar IC <subscript>50</subscript> values indicating they are specific RT inhibitors. Preliminary structure-activity relationships and modeling studies of these new analogues provide valuable avenues for future molecular optimization.<br /> (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)

Subjects :: Anti-HIV Agents chemistry
Carbon-13 Magnetic Resonance Spectroscopy
Cell Line
Humans
Microbial Sensitivity Tests
Molecular Docking Simulation
Proton Magnetic Resonance Spectroscopy
Reverse Transcriptase Inhibitors chemistry
Spectrometry, Mass, Electrospray Ionization
Anti-HIV Agents chemical synthesis
Anti-HIV Agents pharmacology
Drug Design
HIV-1 drug effects
Reverse Transcriptase Inhibitors chemical synthesis
Reverse Transcriptase Inhibitors pharmacology

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