Synthesis and Characterization of a Click-Assembled 18-Atom Macrocycle That Displays Selective AXL Kinase Inhibitory Activity
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Cruz-López, O., Temps, C., Longo, B., Myers, S. H., Franco-Montalban, F., & Unciti-Broceta, A. (2019). Synthesis and Characterization of a Click-Assembled 18-Atom Macrocycle That Displays Selective AXL Kinase Inhibitory Activity. ACS omega.
SponsorshipO.C.-L. and B.L. thank Spain Ministry of Education, Culture and Sport and the Erasmus + Traineeship programme for funding, respectively. C.T. thanks the CMVM for a Principal’s Scholarship. F.F. acknowledges support from Universidad de Granada. SHM and AU-B are grateful to Scottish Power and CRUK for funding.
A novel macrocyclic construct consisting of a pyrazolopyrimidine scaffold concatenated to a benzene ring through two triazoles has been developed to investigate uncharted chemical space with bioactive potential. The 18-atom macrocycle was assembled via a double copper-catalyzed alkyne−azide cycloaddition (CuAAC) reaction between 1,3- bis(azidomethyl)benzene and a bis-propargylated pyrazolo[3,4-d]pyrimidine core. The resulting macrocycle was functionalized further into a multicyclic analog that displays selective inhibitory activity against the receptor tyrosine kinase AXL.