Discovery of Piperidine-linked Quinazoline Derivatives as Po

发布时间：2022-07-22 19:38

　　Acquired immune deficiency syndrome（AIDS）,mainly caused by human immunodeficiency virus type-1（HIV-1）,is still one of the leading causes of death worldwide.The highly active antiretroviral therapy（HAART）regimens,a combination of three or more HIV-1 antiretroviral targeting different steps of active viral replication,is used as the most efficient treatment regimen in controlling HIV-1 replication in infected individuals.Non-nucleoside reverse transcriptase inhibitors（NNRTIs）comprise an important ... 

【文章页数】：127 页

【学位级别】：硕士

【文章目录】：
ABSTRACT
ABBREVIATIONS
CHAPTER 1. INTRODUCTION
    1.1 The Human Immunodeficiency Virus
        1.1.1 HIV-1 Structure
        1.1.2 HIV-1 Replication Cycle and Drug Targets
        1.1.3 U.S FDA Approved HIV Drugs
    1.2 HIV-1 Reverse Transcriptase and Non-nucleoside Reverse TranscriptaseInhibitors
        1.2.1 HIV-1 Reverse Transcriptase Structure and Functions
        1.2.2 HIV-1 Reverse Transcriptase Inhibitors
        1.2.3 Non-nucleoside Reverse Transcriptase Inhibitors
        1.2.4 Drawbacks of Available NNRTIs
        1.2.5 Structural Optimization Strategies of NNRTIs
CHAPTER 2. DESIGN, SYNTHESIS AND BIOLOGICAL EVALUATION OFPIPERIDINE-LINKED QUINAZOLINE DERIVATIVES AS POTENT HIV-1NNRTIs
    2.1 Binding Modes of Diarylpyrimidines
    2.2 Recent Structural Modification of DAPY-lead Compounds Reported by OurGroup
    2.3 Design of Target Compounds
    2.4 Synthesis of Target Compounds
        2.4.1 Instruments and Reagents
        2.4.2 Synthetic Procedure of Target Compounds
        2.4.3 List of Synthesized Compounds
    2.5 Anti-HIV Evaluation of Target Compounds
        2.5.1 Method of Anti-HIV Activity Assay
        2.5.2 Results and Discussion
    2.6 HIV-1 RT Inhibition Assay of Target Compounds
        2.6.1 Method of Recombinant HIV-1 RT Inhibitory Assays
        2.6.2 Results and Discussion
    2.7 Molecular Simulation and Physicochemical Properties Prediction ofRepresentative Compounds
        2.7.1 Molecular Simulation of Representative Compound
        2.7.2 In silico Physicochemical Properties Prediction of RepresentativeCompounds
    2.8 Conclusion
CHAPTER 3. DISCOVERY OF HIV-1 LATENT RESERVOIR ACTIVATORS:DESIGN, SYNTHESIS, AND EVALUATION
    3.1 HIV-1 Latent Reservoirs
    3.2 Establishment and Maintenance of HIV-1 Latent Reservoirs
    3.3 Therapeutics Strategies for an HIV-1 Cure
        3.3.1 Histone Deacetylase Inhibitors (HDACIs)
        3.3.2 Histone Methyltransferase Inhibitors (HMTIs)
    3.4 Design of Target Compounds
    3.5 Synthesis of Target Compounds
        3.5.1 Instruments and Reagents
        3.5.2 Synthetic Route of Target Compounds
    3.6 Latent HIV-1 Activation Assay of Target Compounds
        3.6.1 Method of Latent HIV-1 Activation Assay
        3.6.2 Results and Discussion
    3.7 Conclusion
CHAPTER 4. CONCLUSIONS AND RECOMMENDATIONS
    4.1 Conclusions
    4.2 Recommendations
REFERENCES
APPENDIX
ACKNOWLEDGEMENTS
RELATED PUBLICATIONS AND AWARDS DURING MASTER STUDY
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