Searching for novel N 1 -substituted benzimidazol-2-ones as non-nucleoside HIV-1 RT inhibitors

Bioorganic & Medicinal Chemistry
2017.0

Abstract

Non-nucleoside reverse transcriptase inhibitors (NNRTIs) represent an integral part of the currently available combination antiretroviral therapy (cART) contributing to reduce the AIDS-mortality and turned the disease from lethal to chronic. In this context we recently reported a series of 6-chloro-1-(3-methylphenylsulfonyl)-1,3-dihydro-2H-benzimidazol-2-ones as potent non-nucleoside HIV-1 reverse transcriptase inhibitors. In this paper, we describe the design and the synthesis of two novel series of benzimidazolone analogues in which the linker moiety between the phenyl ring and the sulfonyl group was modified and new small lipophilic groups on the benzyl sulfonyl pendant were introduced. All the new obtained compounds were evaluated as RT inhibitors and were also tested against RTs containing single amino acid mutations. Finally, molecular docking studies were performed in order to rationalize the observed activity of the most promising compound.

Knowledge Graph

Similar Paper

Searching for novel N 1 -substituted benzimidazol-2-ones as non-nucleoside HIV-1 RT inhibitors
Bioorganic & Medicinal Chemistry 2017.0
Novel N1-substituted 1,3-dihydro-2H-benzimidazol-2-ones as potent non-nucleoside reverse transcriptase inhibitors
Bioorganic & Medicinal Chemistry 2008.0
Novel 1,3-dihydro-benzimidazol-2-ones and their analogues as potent non-nucleoside HIV-1 reverse transcriptase inhibitors
Bioorganic & Medicinal Chemistry 2010.0
Design and synthesis of N1-aryl-benzimidazoles 2-substituted as novel HIV-1 non-nucleoside reverse transcriptase inhibitors
Bioorganic & Medicinal Chemistry 2014.0
Design, synthesis, and structure–activity relationships of 1,3-dihydrobenzimidazol-2-one analogues as anti-HIV agents
Bioorganic & Medicinal Chemistry 2009.0
Structural optimization of N1-aryl-benzimidazoles for the discovery of new non-nucleoside reverse transcriptase inhibitors active against wild-type and mutant HIV-1 strains
Bioorganic & Medicinal Chemistry 2018.0
Discovery of novel benzimidazolones as potent non-nucleoside reverse transcriptase inhibitors active against wild-type and mutant HIV-1 strains
Bioorganic & Medicinal Chemistry Letters 2007.0
Synthesis, Biological Activity, and Crystal Structure of Potent Nonnucleoside Inhibitors of HIV-1 Reverse Transcriptase That Retain Activity against Mutant Forms of the Enzyme
Journal of Medicinal Chemistry 2007.0
Molecular docking and antiviral activity of N-substituted benzyl/phenyl-2-(3,4-dimethyl-5,5-dioxidopyrazolo[4,3-c][1,2]benzothiazin-2(4H)-yl)acetamides
Bioorganic & Medicinal Chemistry Letters 2015.0
Aryl Substituted Benzimidazolones as Potent HIV-1 Non-Nucleoside Reverse Transcriptase Inhibitors
ACS Medicinal Chemistry Letters 2019.0