Chemical space exploration of novel naphthyl-carboxamide-diarylpyrimidine derivatives with potent anti-HIV-1 activity.

Authors :: Sang Y
Pannecouque C
De Clercq E
Zhuang C
Chen F
Source :: Bioorganic chemistry [Bioorg Chem] 2021 Jun; Vol. 111, pp. 104905. Date of Electronic Publication: 2021 Apr 20.
Publication Year :: 2021
Abstract: Fifteen naphthyl-carboxamide-DAPYs were generated to explore chemical space in reverse transcriptase (RT) binding site via lead optimization strategy. They displayed up to single-digit nanomolar activity against wild-type (WT) and rilpivirine-associated resistant mutant E138K viruses, as well as potent inhibitory ability toward the RT enzyme. Compound a1 showed exceptionally inhibitory effects with an EC <subscript>50</subscript> value of 3.7 nM against HIV-1 wt strain, and an EC <subscript>50</subscript> of 11 nM targeting mutant E138K. The structure-activity relationships (SARs) of the newly obtained DAPYs were also investigated. Molecular docking analysis elucidated the biological activity and offered a structural insight for follow-up research.<br /> (Copyright © 2021 Elsevier Inc. All rights reserved.)

Subjects :: Anti-HIV Agents chemical synthesis
Anti-HIV Agents chemistry
Dose-Response Relationship, Drug
Microbial Sensitivity Tests
Molecular Docking Simulation
Molecular Structure
Naphthalenes chemical synthesis
Naphthalenes chemistry
Pyrimidines chemical synthesis
Pyrimidines chemistry
Structure-Activity Relationship
Anti-HIV Agents pharmacology
HIV drug effects
Naphthalenes pharmacology
Pyrimidines pharmacology

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