Title Page
Abstract
Contents
Ⅰ. Introduction 8
1.1. Toll-like receptors as drug targets 8
1.2. TLR7 and TLR8 8
1.3. TLR7/8 agonists 9
Ⅱ. Results and Discussion 10
2.1. Chemistry 10
2.2. Structure-activity relationship study 12
2.3. ELISA for detection of mouse IL-6 and TNF-alpha 21
Ⅲ. Conclusion 21
Ⅳ. Experimental procedures 22
4.1. General 22
4.2. Synthetic Procedures and 1H NMR spectra 22
4.2.1. General procedure for preparation of compounds 10a-j 22
4.2.2. General procedure for preparation of compounds 16a-e 29
4.2.3. General procedure for preparation of compound 22 31
4.2.4. General procedure for preparation of compounds 27a-g 33
Ⅴ. References 39
Table 1. In vitro test result of compounds 10a-j 13
Table 2. In vitro test result of compounds 16a-e and 22 16
Table 3. In vitro test result of compounds 27a-g 19
Figure 1. Chemical structure of representative TLR7/8 agonists 8
Figure 2. Schematic illustration of TLR7/8 activation mechanism 9
Figure 3. Predicted binding mode of 10e in TLR7 18
Figure 4. Detection of mouse IL-6 and TNF-alpha in mouse macrophage by ELISA 21
Scheme 1. Synthesis of compounds 10a-j 10
Scheme 2. Synthesis of compounds 16a-e 11
Scheme 3. Synthesis of compound 22 12
Scheme 4. Synthesis of compounds 27a-g 12