The TAM subfamily of Receptor Tyrosine Kinases (RTKs) contains three human 
proteins of therapeutical interest, Axl, Mer, and Tyro3. Our goal was to design 
a type II inhibitor specific for this family, i.e. able to interact with the 
allosteric pocket and with the hinge region of the kinase. We report the 
synthesis of several series of purine analogues of BMS-777607. The structural 
diversity of the designed inhibitors was expected to modify the interactions 
formed in the binding site and consequently to modulate their selectivity 
profiles. The most potent inhibitor 6g exhibits Kds of 39, 42, 65 and 200 nM 
against Axl, Mer, Met and Tyro3 respectively. Analysis of the affinity of 6g for 
active and inactive forms of Abl1, an RTK protein that does not belong to the 
TAM subfamily, together with the binding modes of 6g predicted by docking 
studies, indicates that 6g displays some selectivity for the TAM family and may 
act as a type II inhibitor.