Synthesis of pyrazoles and isoxazoles as potent αvβ3 receptor antagonists

We describe a series of pyrazole and isoxazole analogs as antagonists of the α v β 3 receptor. Compounds showed low to sub-nanomolar potency against α v β 3 , as well as good selectivity against α IIb β 3 . In HT29 cells, most analogs also demonstrated significant selectivity against α v β 6 . Several compounds showed good pharmacokinetic properties in rats, in addition to anti-angiogenic activity in a mouse corneal micropocket model. Compounds were synthesized in a straightforward manner from readily available glutarate precursors.