| 摘要 | 第5-7页 |
| ABSTRACT | 第7-8页 |
| Chapter 1 Introduction | 第12-26页 |
| 1.1 Human African Trypanosomiasis (HAT) | 第12-18页 |
| 1.1.1 Introduction | 第12-13页 |
| 1.1.2 Trypanosoma brucei (T. brucei) | 第13-14页 |
| 1.1.3 Clinical features and diagnosis | 第14-15页 |
| 1.1.4 Current drug therapy and its limitations | 第15-17页 |
| 1.1.5 New drug candidates for HAT | 第17-18页 |
| 1.2 Aminoacyl-t RNA synthetases (aa RSs) | 第18-25页 |
| 1.2.1 Aminoacyl-t RNA synthetases (aa RSs) as targets | 第18-20页 |
| 1.2.2 Inhibitors of aa RSs in research | 第20-23页 |
| 1.2.3 Leucyl-t RNA synthetase (Leu RS) and its inhibitors | 第23-25页 |
| 1.3 Summary | 第25-26页 |
| Chapter 2 Design and synthesis of N-(4-sulfamoylphenyl)thioureas as T. bruceiLeu RS inhibitors | 第26-48页 |
| 2.1 Discovery of N-(4-sulfamoylphenyl)thioureas as Tb Leu RS inhibitors | 第26-29页 |
| 2.1.1 Discovery of the lead compound by virtual screening andpreliminary structure-activity relationship | 第26-28页 |
| 2.1.2 Interactions between compound 13 and Tb Leu RS | 第28-29页 |
| 2.2 Synthesis of N-(4-sulfamoylphenyl)thiourea derivatives | 第29-31页 |
| 2.3 Structure-activity relationship study of N-(4-sulfamoylphenyl)thioureasinhibitors | 第31-34页 |
| 2.3.1 Structure-activity relationship of N-(4-sulfamoylphenyl)thioureaderivatives | 第31-33页 |
| 2.3.2 Interactions between compound 43 and Tb Leu RS | 第33-34页 |
| 2.4 Experimental section | 第34-47页 |
| 2.4.1 General procedures | 第34页 |
| 2.4.2 Preparation of key compounds | 第34-47页 |
| 2.5 Summary | 第47-48页 |
| Chapter 3 Design and sythesis of N-sulfamoylphenylamides as T. brucei LeuRSinhibitors | 第48-79页 |
| 3.1 Discovery of N-(4-sulfamoylphenyl)amides as Tb Leu RS inhibitors | 第48-50页 |
| 3.1.1 Discovery of N-(4-sulfamoylphenyl)amide and preliminarystructure-activity relationship | 第48-49页 |
| 3.1.2 Interactions between compound 51 and Tb Leu RS | 第49-50页 |
| 3.2 Synthesis of N-sulfamoylphenylamide derivatives | 第50-51页 |
| 3.3 Structure-activity relationship study of N-sulfamoylphenylamidesinhibitors | 第51-59页 |
| 3.3.1 Structure-activity relationship of N-sulfamoylphenylamidederivatives | 第51-57页 |
| 3.3.2 Interactions between compound 79, 96, 106 and Tb Leu RS | 第57-59页 |
| 3.4 Experimental section | 第59-78页 |
| 3.4.1 General procedures | 第59页 |
| 3.4.2 Preparation of key compounds | 第59-78页 |
| 3.5 Summary | 第78-79页 |
| Chapter 4 Biological assays | 第79-81页 |
| In vitro aminoacylation assay | 第79-81页 |
| Conclusions | 第81-83页 |
| References | 第83-87页 |
| Appendix | 第87-89页 |
| List of Symbols/Abbreviations | 第87-89页 |
| NMR | 第89-133页 |
| Acknowledgements | 第133-134页 |
| Publications | 第134页 |
