Design And Synthesis Of 2-Amino-7, 8-Dihydropyrido[4, 3-d]Pyrimidine-6(5H)-YL-Alkoxyl Diaryl Urea Derivatives

The development and actioning mechanism of tumor angiogenesis inhibitors(TAI) were briefly introduced,and the progress in the studies on tyrosine kinase inhibitors(TKIs) was described in detail in this thesis.Particularly,the design and synthesis of 2-amino-7,8-dihydropyrido[4,3-d]pyrimidine-6(5H)-yl alkoxyl diaryl urea derivatives were introduced.Based on the analysis of SARs of diaryl urea reported,the active essential group diaryl urea was retained.2-amino-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine alkoxyl were introduced into 4’-position of 1-phenyl,and varied substituents were linked at different positions of 3-phenyl.As a result,we designed and synthesized a series of 2-amino-7,8-dihydropyrido[4,3-d]pyrimidine-6(5H)-yl alkoxyl diaryl urea derivatives. With p-nitrophenol as the starting material,a new synthetic route was developed and 20 target compounds which have not been reported in literatures were synthesized by six steps, including O-alkylation,N-alkylation,condensation,cyclization,reduction and addition. The structures of the target compounds were confirmed by MS and ~1H-NMR.The pharmacological evaluation of these target compounds is undergoing...