Dissertation > Medicine, health > Pharmacy > Drug basic science > Medicinal Chemistry

Design, synthesis and biological activity of imidazo [ 1,2- a ] pyridine Derivatives

Author ZhangZuo
Tutor HuYongZhou
School Zhejiang University
Course Drug analysis
Keywords imidazo[1,2-a]pyridine biological activity studies anti-tumor anti-virus synthetic methodology
CLC R914
Type PhD thesis
Year 2007
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The imidzao[1,2-a]pyridine moiety is widely used in the medicinally useful agents. Imidazo[1,2-a]pyridine derivatives have a wide range of biologically actives and some of them are marketed medicines. In this thesis, the studies are carried on the imidazo[1,2-a]pyridine-based structures, including design and synthesis of imidazo[1,2-a]pyridine derivatives for certain biologically actives, synthetic methodology for novel imidazo[1,2-a]pyridine derivatives.The first part is the biological activity studies of imidazo[1,2-a]pyridine derivatives in recent years.The second part is the design, synthesis, and anti-tumor activity studies of N-imidazo[1,2-a]pyridineyl sulfonamide derivatives. We designed two classes of new compounds, which were based on the lead compound E7070. The first class of compounds, N-( imidazo[1,2-a]pyridine-8-yl) sulfonamide derivatives, were obtained by replacing the indole moiety of E7070 with imidazo[1,2-a]pyridine. The second class of compounds, N-(imidazo[1,2-a]pyridine-5-yl) sulfonamide derivatives, were obtained by changing the position of nitrogen in imidazo[1,2-a]pyridine to investigate the influence of nitrogen’ position on the anti-tumor activity. In vitro biological evaluation indicated that some of these new compounds existed anti-tumor activity. The SAR studies demonstrated that the position of the nitrogen plays a crucial role for anti-tumor activity.The third part is the design, synthesis and biologically actives studies of another kind of imidazo[1,2-a]pyridine derivatives. We optimized the imidazo[1,2-a]pyridine derivatives bearing 3-arylalkylthiomethyl side chain for the better antiviral activities. Three classes of compounds were designed, including thioethers, sulfides and sulfones. In vitro biological evaluation indicated that some of these new compounds existed activity against herpes simplex virus type 1 (HSV-1). Besides, in vitro biological evaluation indicated that some of these new compounds existed anti-tumor activity and certain structure-activity relationship was proposed.The fourth part is about the synthetic methodologies of two classes of novel imidazo[1,2-a]pyridine derivatives. This part of research was based on an unexpected result which had been found during the studies of the second part. And we developed an efficient synthetic method of bis-imidazo[1,2-a]pyridinylmethanes and an efficient method for the preparation of novel C-3 vinylic derivatives of imidazo[1,2-a]pyridines.

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