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.
Inglis
Steven R
SR
Discipline of Chemistry, School of Chemistry and Physics, The University of Adelaide, SA 5005, Australia.
Jones
Rhiannon K
RK
Booker
Grant W
GW
Pyke
Simon M
SM
D000634:Aminoquinolines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D015195:Drug Design; D008024:Ligands; D015394:Molecular Structure; D011505:Protein-Tyrosine Kinases / Q000187:drug effects*; D013329:Structure-Activity Relationship; D018909:src Homology Domains / Q000187:drug effects
D000634:Aminoquinolines; D008024:Ligands; C089848:Tec protein-tyrosine kinase; D011505:Protein-Tyrosine Kinases