BIOMAT Database Logo BIOMAT Database Logo

Novel pyridinone derivatives as non-nucleoside reverse transcriptase inhibitors (NNRTIs) with high potency against NNRTI-resistant HIV-1 strains. 2013

Amin Li, and Yabo Ouyang, and Ziyun Wang, and Yuanyuan Cao, and Xiangyi Liu, and Li Ran, and Chao Li, and Li Li, and Liang Zhang, and Kang Qiao, and Weisi Xu, and Yang Huang, and Zhili Zhang, and Chao Tian, and Zhenming Liu, and Shibo Jiang, and Yiming Shao, and Yansheng Du, and Liying Ma, and Xiaowei Wang, and Junyi Liu
Department of Chemical Biology, School of Pharmaceutical Sciences.

Novel 6-substituted-4-cycloalkyloxy-pyridin-2(1H)-ones were synthesized as non-nucleoside reverse transcriptase inhibitors (NNRTIs), and their biological activity was evaluated. Most of the compounds, especially 26 and 22, bearing a 3-isopropyl and 3-iodine group, respectively, exhibited highly potent activity against wild-type HIV-1 strains and those resistant to reverse transcriptase inhibitors (RTIs). The diastereoisomers of 26-trans and 26-cis were synthesized separately and confirmed with HPLC and NOESY spectra. The 26-trans isomers had an activity about 400-fold more potent than that of 26-cis. The pair of 26-trans enantiomers, one of the most potent inhibitors with EC50 of 4 nM and selectivity index (SI) of 75000, was highly effective against a panel of RTIs-resistant strains with single (Y181C and K103N) or double (A17) mutations in reverse transcriptase. The results suggest that these novel pyridinone derivatives have the potential to be further developed as new antiretroviral drugs with improved antiviral efficacy and drug resistance profile.

UI MeSH Term Description Entries
D008958 Models, Molecular Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures. Molecular Models,Model, Molecular,Molecular Model
D011487 Protein Conformation The characteristic 3-dimensional shape of a protein, including the secondary, supersecondary (motifs), tertiary (domains) and quaternary structure of the peptide chain. PROTEIN STRUCTURE, QUATERNARY describes the conformation assumed by multimeric proteins (aggregates of more than one polypeptide chain). Conformation, Protein,Conformations, Protein,Protein Conformations
D011728 Pyridones Pyridine derivatives with one or more keto groups on the ring. Pyridinones
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
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
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
D024882 Drug Resistance, Viral The ability of viruses to resist or to become tolerant to chemotherapeutic agents or antiviral agents. This resistance is acquired through gene mutation. Antiviral Drug Resistance,Antiviral Drug Resistances,Drug Resistances, Viral

Related Publications

Amin Li, and Yabo Ouyang, and Ziyun Wang, and Yuanyuan Cao, and Xiangyi Liu, and Li Ran, and Chao Li, and Li Li, and Liang Zhang, and Kang Qiao, and Weisi Xu, and Yang Huang, and Zhili Zhang, and Chao Tian, and Zhenming Liu, and Shibo Jiang, and Yiming Shao, and Yansheng Du, and Liying Ma, and Xiaowei Wang, and Junyi Liu
Novel indole-3-sulfonamides as potent HIV non-nucleoside reverse transcriptase inhibitors (NNRTIs).
January 2008, Bioorganic & medicinal chemistry letters,
Amin Li, and Yabo Ouyang, and Ziyun Wang, and Yuanyuan Cao, and Xiangyi Liu, and Li Ran, and Chao Li, and Li Li, and Liang Zhang, and Kang Qiao, and Weisi Xu, and Yang Huang, and Zhili Zhang, and Chao Tian, and Zhenming Liu, and Shibo Jiang, and Yiming Shao, and Yansheng Du, and Liying Ma, and Xiaowei Wang, and Junyi Liu
[Progress in HIV non-nucleoside reverse transcriptase inhibitors (NNRTIs)].
August 2004, Yao xue xue bao = Acta pharmaceutica Sinica,
Amin Li, and Yabo Ouyang, and Ziyun Wang, and Yuanyuan Cao, and Xiangyi Liu, and Li Ran, and Chao Li, and Li Li, and Liang Zhang, and Kang Qiao, and Weisi Xu, and Yang Huang, and Zhili Zhang, and Chao Tian, and Zhenming Liu, and Shibo Jiang, and Yiming Shao, and Yansheng Du, and Liying Ma, and Xiaowei Wang, and Junyi Liu
Discovery of Phenylaminopyridine Derivatives as Novel HIV-1 Non-nucleoside Reverse Transcriptase Inhibitors.
August 2012, ACS medicinal chemistry letters,
Amin Li, and Yabo Ouyang, and Ziyun Wang, and Yuanyuan Cao, and Xiangyi Liu, and Li Ran, and Chao Li, and Li Li, and Liang Zhang, and Kang Qiao, and Weisi Xu, and Yang Huang, and Zhili Zhang, and Chao Tian, and Zhenming Liu, and Shibo Jiang, and Yiming Shao, and Yansheng Du, and Liying Ma, and Xiaowei Wang, and Junyi Liu
Discovery of diarylpyridine derivatives as novel non-nucleoside HIV-1 reverse transcriptase inhibitors.
September 2009, Bioorganic & medicinal chemistry letters,
Amin Li, and Yabo Ouyang, and Ziyun Wang, and Yuanyuan Cao, and Xiangyi Liu, and Li Ran, and Chao Li, and Li Li, and Liang Zhang, and Kang Qiao, and Weisi Xu, and Yang Huang, and Zhili Zhang, and Chao Tian, and Zhenming Liu, and Shibo Jiang, and Yiming Shao, and Yansheng Du, and Liying Ma, and Xiaowei Wang, and Junyi Liu
Novel Cyclopropyl-Indole Derivatives as HIV Non-Nucleoside Reverse Transcriptase Inhibitors.
June 2012, ACS medicinal chemistry letters,
Amin Li, and Yabo Ouyang, and Ziyun Wang, and Yuanyuan Cao, and Xiangyi Liu, and Li Ran, and Chao Li, and Li Li, and Liang Zhang, and Kang Qiao, and Weisi Xu, and Yang Huang, and Zhili Zhang, and Chao Tian, and Zhenming Liu, and Shibo Jiang, and Yiming Shao, and Yansheng Du, and Liying Ma, and Xiaowei Wang, and Junyi Liu
New pyridinone derivatives as potent HIV-1 nonnucleoside reverse transcriptase inhibitors.
June 2009, Journal of medicinal chemistry,
Amin Li, and Yabo Ouyang, and Ziyun Wang, and Yuanyuan Cao, and Xiangyi Liu, and Li Ran, and Chao Li, and Li Li, and Liang Zhang, and Kang Qiao, and Weisi Xu, and Yang Huang, and Zhili Zhang, and Chao Tian, and Zhenming Liu, and Shibo Jiang, and Yiming Shao, and Yansheng Du, and Liying Ma, and Xiaowei Wang, and Junyi Liu
Current and emerging non-nucleoside reverse transcriptase inhibitors (NNRTIs) for HIV-1 treatment.
October 2019, Expert opinion on drug metabolism & toxicology,
Amin Li, and Yabo Ouyang, and Ziyun Wang, and Yuanyuan Cao, and Xiangyi Liu, and Li Ran, and Chao Li, and Li Li, and Liang Zhang, and Kang Qiao, and Weisi Xu, and Yang Huang, and Zhili Zhang, and Chao Tian, and Zhenming Liu, and Shibo Jiang, and Yiming Shao, and Yansheng Du, and Liying Ma, and Xiaowei Wang, and Junyi Liu
Non-nucleoside reverse transcriptase inhibitors: the NNRTI boom.
November 1999, Antiviral chemistry & chemotherapy,
Amin Li, and Yabo Ouyang, and Ziyun Wang, and Yuanyuan Cao, and Xiangyi Liu, and Li Ran, and Chao Li, and Li Li, and Liang Zhang, and Kang Qiao, and Weisi Xu, and Yang Huang, and Zhili Zhang, and Chao Tian, and Zhenming Liu, and Shibo Jiang, and Yiming Shao, and Yansheng Du, and Liying Ma, and Xiaowei Wang, and Junyi Liu
Novel benzophenones as non-nucleoside reverse transcriptase inhibitors of HIV-1.
February 2004, Journal of medicinal chemistry,
Amin Li, and Yabo Ouyang, and Ziyun Wang, and Yuanyuan Cao, and Xiangyi Liu, and Li Ran, and Chao Li, and Li Li, and Liang Zhang, and Kang Qiao, and Weisi Xu, and Yang Huang, and Zhili Zhang, and Chao Tian, and Zhenming Liu, and Shibo Jiang, and Yiming Shao, and Yansheng Du, and Liying Ma, and Xiaowei Wang, and Junyi Liu
QSAR study on pyridinone derivatives as HIV-1 non-nucleoside reverse transcriptase inhibitor: a mixed approach.
May 2007, Medicinal chemistry (Shariqah (United Arab Emirates)),
Copied contents to your clipboard!