Design and synthesis of novel potent and selective integrin alphanubeta3 antagonists--novel synthetic routes to isoquinolinone, benzoxazinone, and quinazolinone acetates.
An unexpected ring contraction of benzazepinone based alpha(nu)beta(3) antagonists led to the design of quinolinone-type derivatives. Novel and efficient synthetic routes to isoquinolinone, benzoxazinone, and quinazolinone acetates were established. Nanomolar alpha(nu)beta(3) antagonists based on these new scaffolds were prepared. Moreover, benzoxazinones 15a and 15b exhibited high microsomal stability and good permeability.
Seitz
Werner
W
BASF AG, Main Research Laboratory, D-67056 Ludwigshafen, Germany.
Geneste
Hervé
H
Backfisch
Gisela
G
Delzer
Jürgen
J
Graef
Claudia
C
Hornberger
Wilfried
W
Kling
Andreas
A
Subkowski
Thomas
T
Zimmermann
Norbert
N
D048588:Benzoxazines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D015195:Drug Design; D004797:Enzyme-Linked Immunosorbent Assay; D039302:Integrin alphaVbeta3 / Q000037:antagonists & inhibitors*; D007546:Isoquinolines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D011799:Quinazolines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D013329:Structure-Activity Relationship
D048588:Benzoxazines; D039302:Integrin alphaVbeta3; D007546:Isoquinolines; D011799:Quinazolines