BIOMAT Database Logo BIOMAT Database Logo

[Design, synthesis and biologic evaluation of diarylbenzimidazole derivatives as novel HIV-1 non-nucleoside reverse transcriptase inhibitors]. 2009

Bing-jie Qin, and Ting Zhou, and Hong Lu, and Shi-bo Jiang, and Lan Xie
Institute ofPharmacology and Toxicology, Academy of Military Medical Sciences, Beijing 100850, China.

Twenty seven new diarylbenzimidazole derivatives (A1-A21, B1-B6) were designed, synthesized, and evaluated in MT-2 cell line as potential HIV-1 non-nucleoside reverse transcriptase inhibitors (NNRTIs) agents with a new skeleton based on molecular modeling technique and hit 1,2-diarylbenzimidazole A1 (EC50 69.9 miromol x L(-1)). Hence, 1,2-diarylbenzimidazoles A6 and B3, and 1,6-diarylbenzimidazole B6 showed obvious potency against HIV-1 replication in MT-2 cell line with EC50 values of 15.33, 9.81 and 1.37 micromol x L(-1) respectively. All target compounds were synthesized commonly from substituted 2-nitroanilines by 1-3 steps under mild reaction conditions. Current studies provided preliminary SAR, thus indicating that 1,6-diaryl substitution on the benzimidazole ring would be a right direction for further modification. Furthermore, the docking studies demonstrated that B6 could fit well into the HIV-1 NNRTI binding pocket with a similar binding orientation and conformation to that of TMC278, a promising NNRTI candidate inclinical trial III, Therefore, active compound B6 could serve as a new starting point to develop a series of 1,6-diarylbenzimidazole derivatives as HIV-1 NNRTI agents with a novel skeleton.

UI MeSH Term Description Entries
D002460 Cell Line Established cell cultures that have the potential to propagate indefinitely. Cell Lines,Line, Cell,Lines, Cell
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D001562 Benzimidazoles Compounds with a BENZENE fused to IMIDAZOLES.
D013329 Structure-Activity Relationship The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups. Relationship, Structure-Activity,Relationships, Structure-Activity,Structure Activity Relationship,Structure-Activity Relationships
D014779 Virus Replication The process of intracellular viral multiplication, consisting of the synthesis of PROTEINS; NUCLEIC ACIDS; and sometimes LIPIDS, and their assembly into a new infectious particle. Viral Replication,Replication, Viral,Replication, Virus,Replications, Viral,Replications, Virus,Viral Replications,Virus Replications
D015195 Drug Design The molecular designing of drugs for specific purposes (such as DNA-binding, enzyme inhibition, anti-cancer efficacy, etc.) based on knowledge of molecular properties such as activity of functional groups, molecular geometry, and electronic structure, and also on information cataloged on analogous molecules. Drug design is generally computer-assisted molecular modeling and does not include PHARMACOKINETICS, dosage analysis, or drug administration analysis. Computer-Aided Drug Design,Computerized Drug Design,Drug Modeling,Pharmaceutical Design,Computer Aided Drug Design,Computer-Aided Drug Designs,Computerized Drug Designs,Design, Pharmaceutical,Drug Design, Computer-Aided,Drug Design, Computerized,Drug Designs,Drug Modelings,Pharmaceutical Designs
D015394 Molecular Structure The location of the atoms, groups or ions relative to one another in a molecule, as well as the number, type and location of covalent bonds. Structure, Molecular,Molecular Structures,Structures, Molecular
D015497 HIV-1 The type species of LENTIVIRUS and the etiologic agent of AIDS. It is characterized by its cytopathic effect and affinity for the T4-lymphocyte. Human immunodeficiency virus 1,HIV-I,Human Immunodeficiency Virus Type 1,Immunodeficiency Virus Type 1, Human
D054303 HIV Reverse Transcriptase A reverse transcriptase encoded by the POL GENE of HIV. It is a heterodimer of 66 kDa and 51 kDa subunits that are derived from a common precursor protein. The heterodimer also includes an RNAse H activity (RIBONUCLEASE H, HUMAN IMMUNODEFICIENCY VIRUS) that plays an essential role the viral replication process. Reverse Transcriptase, HIV,Reverse Transcriptase, Human Immunodeficiency Virus,Transcriptase, HIV Reverse
D018894 Reverse Transcriptase Inhibitors Inhibitors of reverse transcriptase (RNA-DIRECTED DNA POLYMERASE), an enzyme that synthesizes DNA on an RNA template. Reverse Transcriptase Inhibitor,Inhibitors, Reverse Transcriptase,Inhibitor, Reverse Transcriptase,Transcriptase Inhibitor, Reverse

Related Publications

Bing-jie Qin, and Ting Zhou, and Hong Lu, and Shi-bo Jiang, and Lan Xie
Synthesis of novel uracil non-nucleoside derivatives as potential reverse transcriptase inhibitors of HIV-1.
November 2009, Archiv der Pharmazie,
Bing-jie Qin, and Ting Zhou, and Hong Lu, and Shi-bo Jiang, and Lan Xie
Discovery of Phenylaminopyridine Derivatives as Novel HIV-1 Non-nucleoside Reverse Transcriptase Inhibitors.
August 2012, ACS medicinal chemistry letters,
Bing-jie Qin, and Ting Zhou, and Hong Lu, and Shi-bo Jiang, and Lan Xie
Discovery of diarylpyridine derivatives as novel non-nucleoside HIV-1 reverse transcriptase inhibitors.
September 2009, Bioorganic & medicinal chemistry letters,
Bing-jie Qin, and Ting Zhou, and Hong Lu, and Shi-bo Jiang, and Lan Xie
Synthesis and biological evaluation of (±)-benzhydrol derivatives as potent non-nucleoside HIV-1 reverse transcriptase inhibitors.
August 2011, Bioorganic & medicinal chemistry,
Bing-jie Qin, and Ting Zhou, and Hong Lu, and Shi-bo Jiang, and Lan Xie
Design, synthesis, and biological evaluations of novel quinolones as HIV-1 non-nucleoside reverse transcriptase inhibitors.
August 2006, Bioorganic & medicinal chemistry letters,
Bing-jie Qin, and Ting Zhou, and Hong Lu, and Shi-bo Jiang, and Lan Xie
Arylazolylthioacetanilide. Part 11: design, synthesis and biological evaluation of 1,2,4-triazole thioacetanilide derivatives as novel non-nucleoside HIV-1 reverse transcriptase inhibitors.
November 2013, Medicinal chemistry (Shariqah (United Arab Emirates)),
Bing-jie Qin, and Ting Zhou, and Hong Lu, and Shi-bo Jiang, and Lan Xie
Novel Cyclopropyl-Indole Derivatives as HIV Non-Nucleoside Reverse Transcriptase Inhibitors.
June 2012, ACS medicinal chemistry letters,
Bing-jie Qin, and Ting Zhou, and Hong Lu, and Shi-bo Jiang, and Lan Xie
Synthesis and biological evaluation of imidazole thioacetanilides as novel non-nucleoside HIV-1 reverse transcriptase inhibitors.
August 2009, Bioorganic & medicinal chemistry,
Bing-jie Qin, and Ting Zhou, and Hong Lu, and Shi-bo Jiang, and Lan Xie
Design, synthesis, and evaluation of diarylpyridines and diarylanilines as potent non-nucleoside HIV-1 reverse transcriptase inhibitors.
December 2010, Journal of medicinal chemistry,
Bing-jie Qin, and Ting Zhou, and Hong Lu, and Shi-bo Jiang, and Lan Xie
Synthesis and biological evaluation of piperidine-substituted triazine derivatives as HIV-1 non-nucleoside reverse transcriptase inhibitors.
May 2012, European journal of medicinal chemistry,
Copied contents to your clipboard!