dc.description.abstract | Many disease and death around the world caused by viruses are major problems of human being. However, because of fast mutation rate of the RNA viruses, there are lack of suitable drugs and vaccines to control them. To solve these problems, Seventh Framework Programme in European Union has proved a project that focus on drugs discovery towards dengue-, entero- and paramyxoviruses. We are participating in this program, so called SILVER, and devoting our efforts on drugs development in our laboratory.
In the research of drugs designing, scientists currently focus on the nitrogen–containing heterocycles, which contain various bioactivities. Moreover, our laboratory synthesized a series of nucleoside–coumarin conjugates, which exhibited potent activity on HCV. Therefore, I synthesized adenosine conjugated nitrogen–containing heterocycles, adenosine–TBBT 23, adenosine–TBBT 24, adenosine–HBB 28, adenine–TBBT 25 and adenine–TBBT 26, with thioalkyl linker as antiviral agent candidates. The synthetic method was a nucleophilic substitution in basic condition with 8-mercaptoadenosine as a nucleophile and heterocycles containing a leaving group as a electrophile. The target structures was checked by nuclear magnetic resonance and high resolution mass spectrometers.
On the other hand, I discussed the N-1 and N-2 tautomerization of benzotriazole when reacted with formaldehyde. I also discussed phenomena of the chemical shift of 8-[(4’’,5’’,6’’,7’’-tetrabromobenzotriazol-1’’-yl)methylthio]adenosine (23) and 8-[(benzimidazol- 2’’-yl)(phenyl)methylthio]adenosine (28) in nuclear magnetic resonance spectroscopy. Finally, the reactivity of nucleophilic substitution with 8-mercaptoadenosine (22) in different pH values is also discussed.
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