Synthesis of N-benzylated-2-aminoquinolines as ligands for the Tec SH3 domain

In recent work, we have been developing 2-aminoquinolines as ligands for Src Homology 3 (SH3) domains, so far the only reported examples of small-molecule ligands for these domains. In this paper, we report the synthesis of a series of N-benzylated-2-aminoquinolines by reductive amination of aryl aldehydes with 2-aminoquinoline. These ligands bound the SH3 domain with ca. one and a half to twofold reduced affinity relative to 2-aminoquinoline; however, some evidence was found to suggest that the benzylic substituents made new contacts with the SH3 domain surface. These results provide useful SAR information that may assist in future ligand design.