Design and synthesis of novel potent and selective integrin αvβ3 antagonists—Novel synthetic routes to isoquinolinone, benzoxazinone, and quinazolinone acetates

An unexpected ring contraction of benzazepinone based αvβ3 antagonists led to the design of quinolinone-type derivatives. Novel and efficient synthetic routes to isoquinolinone, benzoxazinone, and quinazolinone acetates were established. Nanomolar αvβ3 antagonists based on these new scaffolds were prepared. Moreover, benzoxazinones 15a and 15b exhibited high microsomal stability and good permeability.

Graphical abstractAn unexpected ring contraction of benzazepinone based αvβ3 antagonists led to the design of quinolinone-type derivatives (X = CH2, O, NH). Novel and efficient synthetic routes to isoquinolinone, benzoxazinone, and quinazolinone acetates were established. Nanomolar αvβ3 antagonists based on these new scaffolds were prepared. Moreover, benzoxazinones (X = O) 15a and 15b exhibited high microsomal stability and good permeability.Figure optionsDownload full-size imageDownload as PowerPoint slide